Percutaneous nephrolithotomy in children.

Percutaneous nephrolithotomy was performed on 18 children with renal calculi. No mortality resulted from this procedure and hemorrhage was the major complication. At the end of treatment 67% of the patients were stone-free and 82% of targeted stones were removed. Percutaneous nephrolithotomy can be considered a successful treatment in the management of the pediatric patient with renal calculi.


Percutaneous management of urolithiasis during pregnancy.

A total of 6 pregnant women with obstructing urinary calculi was managed by percutaneous nephrostomy drainage placed under ultrasound guidance with the patient under local anesthesia. All patients initially had relief of acute obstruction. However, occlusion of the percutaneous nephrostomy tubes with debris necessitated tube changes in 5 of 6 patients. In 2 patients recurrent nephrostomy tube obstruction, fever and pain led to percutaneous stone removal during pregnancy. In the remaining 4 patients the nephrostomy tubes were left indwelling through delivery. During the postpartum period 3 patients successfully underwent ureteroscopic stone extraction and 1 passed the stone spontaneously. Bacteriuria developed in each patient despite the use of preventive antibiotics. All 6 women had uncomplicated vaginal deliveries of healthy newborns and are currently asymptomatic with no evidence of obstruction. Percutaneous drainage of an acutely obstructed kidney in a pregnant woman is an effective temporizing alternative to ureteral stent placement until definitive treatment can be performed.


Management of urinary calculi during pregnancy.

Renal calculous disease is an infrequent but not insignificant occurrence during pregnancy. In 50 to 80% of the cases conservative management is appropriate and the stone will pass spontaneously. Should intervention be required, recent advances in stone management and techniques for urinary tract drainage may be successfully applied to the obstetric population. Concerns regarding surgical and anesthetic risks, and the potential hazards of radiation exposure during pregnancy favor a minimally invasive approach with definitive treatment late in pregnancy or post partum. We review our experience during a 5-year period in managing 29 patients with urinary calculous disease during pregnancy. Based on our experience and review of the literature an algorithm for treatment of urolithiasis during pregnancy is proposed.


Mechanisms responsible for diminished fragmentation of ureteral calculi: an experimental and clinical study.

We molded 24 synthetic stones (mean weight 680 mg., range 641 to 715) from a commercial mixture of gypsum, silica, cellulose and polyvinyl acetate. Each stone was subjected to 400 shocks on a Wolf 2300 Piezolith and groups of 6 stones were treated in 4 different modes. Mean amounts fragmented were 243 +/- 18 mg. in a free environment, 62 +/- 18 mg. confined loosely in a latex tube, 22 +/- 8 mg. impacted in the tube and 30 +/- 8 mg. impacted alongside a 7F stent. During a 30-month period 118 patients received in situ extracorporeal shock wave lithotripsy for ureteral calculi using the same lithotriptor. The mean stone burden was 11.4 mm. (range 4 to 29). Success was greater for patients with calculi 10 mm. or less than for those with stones greater than 10 mm. (71% versus 51%, p less than 0.05), despite the former group receiving less shocks (5,404 versus 7,491). The influence of size was then excluded by studying the number of shocks delivered per mm. of calculus. Patients receiving 500 to 699 shocks per mm. showed a higher success rate than those receiving a smaller number of shocks per mm. Treatment with a greater number of shocks per mm. did not improve success rate. The experimental study demonstrated that confinement and impaction significantly diminish the rate of fragmentation of calculi. However, the clinical study suggested that there may be an optimum number of shocks per mm. that should be delivered. Treatment beyond this point fails to improve results. The 28% failure rate even in those receiving the highest number of shocks per mm. suggests that large, impacted calculi are unsuitable for treatment with in situ shock wave lithotripsy on this machine.


Sonographic detection of ureteral calculi in patients with normal excretory urography.

We report 3 cases of nonobstructing distal ureteral calculi diagnosed by sonography in which excretory urography was normal. In each case sonography was performed because of high clinical suspicion for a ureteral stone. In 2 patients a stone was impacted at an edematous ureteral orifice. All 3 patients subsequently passed the stone spontaneously. A high resolution ultrasound examination should be performed on patients with a history suggestive of ureteral calculus despite a normal excretory urogram.


Management of ureteral stones by extracorporeal shock wave lithotripsy using Lithostar lithotriptor.

In 282 patients 290 ureteral stones were treated with extracorporeal shock wave lithotripsy using the Lithostar lithotriptor. Stones were in the upper ureter in 198 units (68.3%), middle ureter in 36 (12.4%) and lower ureter in 56 (19.3%). The average stone mass was 11.9 mm. and the mean number of shock waves was 4,913 for all levels with a mean kv. of 16.9. The average number of sessions was 1.5 for all sites. Auxiliary measures in the form of ureteral catheterization were done in 24 patients (8.5%) and internal stenting in 12 (4.25%), all of whom had upper or middle ureteral stones. Disintegration of the stones was achieved in 99% of the upper, 93.7% of the middle and 91.7% of the lower ureteral stones. However, clearance of fragments within 3 months from the last session was achieved in 94.8% of the upper, 87.5% of the middle and 91.7% of the lower ureteral stones for an overall stone-free rate of 93.3%.


The Swiss Lithoclast: a new device for intracorporeal lithotripsy.

Modalities available for performing intracorporeal lithotripsy include ultrasonic, electrohydraulic and laser procedures. We present our experience with a new and unique technology for performing intracorporeal lithotripsy, namely the Swiss Lithoclast. This simple and inexpensive device uses compressed air to activate a solid probe in a manner similar to that of a jackhammer. We report the use of the Lithoclast in 31 cases, consisting of 6 renal calculi approached percutaneously, 17 ureteral calculi and 8 bladder calculi. The Lithoclast successfully fragmented 94% of the calculi. There were no intraoperative or long-term complications directly related to the use of this device. We have found the Swiss Lithoclast to be a safe, effective and inexpensive means of performing intracorporeal lithotripsy for calculi located throughout the urinary tract.


Cost and efficacy of extracorporeal shock wave lithotripsy versus ureteroscopy in the treatment of lower ureteral calculi.

We retrospectively reviewed the extracorporeal shock wave lithotripsy (ESWL) and ureteroscopy experience relative to cost and efficacy of a group of practitioners skilled in the use of both procedures for the treatment of lower ureteral stones. Although the initial success rate was higher with ureteroscopy, no significant difference could be found in final success or complication rates. The cost of ESWL was approximately 60% higher than that for ureteroscopy (mean $7,320.26 versus $4,568.47, p less than 0.005). Given the current restraints on resources, and the equal efficacy and morbidity of both procedures, ureteroscopy must be considered the procedure of choice in the management of lower ureteral stones.


In situ extracorporeal shock wave lithotripsy of ureteral calculi with the MPL-9000X lithotriptor.

Within the wide armamentarium of urinary stone treatment modalities extracorporeal shock wave lithotripsy (ESWL) has been established as the first line procedure. With the Dornier MPL-9000X lithotriptor one has the choice of ultrasound or fluoroscopic localization of calculi throughout the entire urinary tract. Except for the kidney, ultrasound guidance is preferred for calculi in the distal ureter, while fluoroscopy is generally used on the proximal two-thirds of the ureter. Between January and December 1990, 123 ESWL treatments were performed on 83 patients suffering from ureteral calculi with an average stone size of 9.3 x 6 mm. Median treatment parameters were 1,597 shock waves at 19.3 kv. for 43 minutes. For stones in the upper two-thirds of the ureter sedation analgesia was given, while ESWL on the pelvic ureter did not create intolerable pain. Of the treatments 69% were done on an outpatient basis. In situ ESWL treatment of urinary calculi was successful in 72 patients (86.7%), and 20 patients (24.1%) were treated with multiple treatment sessions. ESWL therapy for 47 stones in the distal ureter showed better results than for 33 stones plus 2 steinstrasse in the proximal part (95.5% versus 80% stone-free rate). Of 4 patients with mid ureteral calculi 2 could be rendered stone-free by ESWL alone. Auxiliary procedures, such as percutaneous nephrostomy or ureteral splints, had to be performed in 15.7%. Final endoscopic stone extraction was done in 7 cases and open surgery in 4, constituting a 13.3% failure rate for ESWL therapy. The results prove that the MPL-9000X lithotriptor is effective for primary noninvasive stone treatment.


Percutaneous management of a nephrocutaneous fistula due to a pyelocaliceal diverticular calculus.

Nephrocutaneous fistulas arising from stone-containing pyelocaliceal diverticula are rare. We describe 2 patients who were treated by open drainage for perirenal abscesses. Subsequently, both patients presented with a nephrocutaneous fistula from a stone-containing pyelocaliceal diverticulum. These patients were successfully treated by percutaneous nephrostolithotomy with fulguration of the diverticula.


Endoscopic and open stone surgery in morbidly obese patients.

Management of urinary stone disease in the morbidly obese patient can be troublesome and problematic. We present 4 recent female patients with an average weight of 442 pounds and an average height of 5 feet 2 inches. The patients underwent a total of 8 open surgical or endoscopic procedures for partial or complete staghorn calculi. Complications encountered included inability to reach the stones with rigid or flexible ureteroscopes, inadvertent incision above the 10th rib for pyelolithotomy, intraoperative rhabdomyolysis during a flank incision, consecutive temporary renal failure and wound infection. We discuss the limitations of extracorporeal shock wave lithotripsy, retrograde endoscopic manipulation, percutaneous antegrade surgery and open surgical approaches. Such patients continue to represent diagnostic challenges and high risk therapeutic options.


Extracorporeal shock wave lithotripsy of radiolucent urinary calculi using the Siemens Lithostar Plus.

Between October 1989 and June 1991, 1,250 patients with urinary calculi were treated at our institution using the Siemens Lithostar. A total of 17 patients (1.37%) with radiolucent or slightly opaque calculi underwent lithotripsy with the Lithostar Plus, which has an overhead electromagnetic generator module and a localization system composed of a real-time on-line 3.5 mHz. ultrasound transducer. The stones were located in the calices in 52.9% of the cases, renal pelvis in 17.7%, ureter in 23.5% and bladder in 5.9%. Followup consisted of a nephrotomogram or ultrasound 1 day and 1 to 3 months postoperatively. Complete removal of all stone fragments was achieved in 76.4% of the cases after 3 months. Retreatment was necessary in 23.5% of the cases. All treatments were performed without anesthesia and hospitalization. Complications were present in 11.8%; perirenal hematoma was noted in 1 patient but this resolved spontaneously within a few days and the same occurred in 1 patient with renal pain. Extracorporeal shock wave lithotripsy using the Lithostar Plus proved to be an effective noninvasive procedure to treat radiolucent and slightly opaque urinary calculi. However, since the Lithostar Plus has a higher power setting, care must be taken to avoid damage with the use of high energy.


An evaluation of 646 stone patients treated on the HM4 extracorporeal shock wave lithotriptor.

Extracorporeal shock wave lithotripsy (ESWL) has become the preferred treatment modality for the majority of urinary tract calculi. This form of treatment boasts excellent patient acceptance and has significantly reduced the need for surgical intervention. An evaluation of our first 646 patients undergoing 722 ESWL treatments at Walter Reed Army Medical Center revealed an overall stone-free rate at 1 and 3 months of 52% and 79%, respectively. The exact location of each stone within the kidney and ureter further determined the stone-free rates at 1 and 3 months. Stone-free rates at 3 months ranged from 89% for renal pelvic stones to 64% for lower pole caliceal stones. Upper third ureteral stones treated in situ without stenting resulted in a 74% stone-free rate at 3 months. This rate increased to 85% when these patients were stented and treated in situ. Although statistically insignificant, when the upper third ureteral stones were manipulated into and treated in the renal pelvis (31% of our patient population) the 3-month stone-free rate increased to 87%. Attempts were made to stent all ureteral stones before treatment. The stone-free rate at 3 months was 86% for mid third ureteral stones and 81% for lower third ureteral stones. The overall retreatment rate was 11.8% with a complication rate of 7.6% and a 6.3% post-ESWL intervention rate (open or percutaneous surgery, stent or percutaneous nephrostomy placement).


Electromagnetic extracorporeal shock wave lithotripsy for calculi in horseshoe kidneys.

Between June 1987 and January 1991, 11 renal units in 10 patients with horseshoe kidneys were managed by electromagnetic extracorporeal shock wave lithotripsy (ESWL) monotherapy with a Siemens Lithostar. A total of 33 calculi was treated in 42 sessions. All treatments were performed without anesthesia and on an outpatient basis. All calculi could be targeted by standard installation techniques. The maximum number of shock waves per session was 4,000, which implies per stone an average of 1.3 sessions and an average of 4,903 shock waves (range 1,800 to 9,000) at a mean energy setting of 17.8 kv. Complete disintegration or fragmentation into spontaneously passable particles was achieved in 27 calculi, for a success rate of 83% when considering the results in regard to the individual stone locations. Per renal unit, an average of 3 calculi were targeted and after an average of 3.8 sessions 6 units became stone-free. Horseshoe kidneys, when calculous, contain dispersed and multiple calculi and from these data approximately 1 session per stone must be planned. The number of treatments per renal unit increased in proportion to the number of calculi and to the presence of calculi with low fragility. Of 21 lower pole calculi 18 completely evacuated and this observation has been related to the more medial location of the inferior calices near the ureteropelvic junction. No impaired drainage of fragments was noted to be related to the horseshoe anatomy. Patency of the ureteropelvic anatomy appeared to be the main parameter for the evacuation of fragments. Neither preoperative nor postoperative adjuvant maneuvers have been necessary.


Extracorporeal shock wave lithotripsy and endoscopic management of renal calculi with urinary diversions.

A total of 12 patients with urinary diversions had calculi in 15 kidneys managed initially by extracorporeal shock wave lithotripsy (ESWL) in 12 kidneys and percutaneous nephrolithotripsy in 3. After 15 treatments with ESWL only 3 of the 12 kidneys (25%) became stone-free. Endoscopic procedures were used in 5 kidneys with fragments remaining after ESWL, and comprised percutaneous ultrasound lithotripsy in 2 and transstomal retrograde manipulations in 3. The 3 initial and 5 subsequent endoscopic procedures resulted in 6 of the 8 kidneys (75%) being stone-free. The poor results with ESWL are due to preexisting dilated upper urinary tracts and to immobility in obese myelomeningocele patients. Endoscopic procedures are the preferred method of treatment in these patients.


Urinary tract status of patients with neurogenic dysfunction presenting with upper tract stone disease.

We treated 71 patients with neurogenic vesical dysfunction between September 1983 and June 1990 for upper tract stones. We studied these patients to determine the time course of stone development and the presence of associated urological abnormalities. There were 44 male and 27 female patients 6 to 72 years old. Lower urinary tract dysfunction resulted from spinal cord injuries in 34 patients (48%), myelodysplasia in 19 (27%), multiple sclerosis in 12 (17%) and other diagnoses in 6 (8%). Of 71 patients 21 (30%) were managed by an ileal loop, 12 (17%) by a Foley catheter, 10 (14%) by a suprapubic tube, 10 (14%) by ureterostomy, 5 (7%) by vesicostomy, 8 (11%) by intermittent catheterization, and 5 (7%) by diaper, Créde's voiding or condom catheterization. Stone disease developed within 1 to 22 years. Patients with an indwelling catheter or supravesical diversion fared worse than those managed by intermittent catheterization or vesicostomy; they had higher rates of renal unit loss, renal parenchymal damage, decreased renal function, hydroureter, and staghorn and bilateral calculi. All of the listed methods of management were contemporaneous, suggesting the continued use of methods proved to be associated with upper tract deterioration.


Multiple large calculi in a continent urinary reservoir: a case report.

Continent urinary reservoirs have increasingly become popular during the last decade but they are associated with long-term complications. We report a case of huge multiple stones in an ileocecal reservoir, which formed as a result of noncompliance with intermittent self-catheterization. An open method was required for removal of the stones to prevent recurrent urosepsis.


The effects of a single evening dose of alkaline citrate on urine composition and calcium stone formation.

The effects on urine composition and pH of a single evening dose of alkaline potassium sodium citrate were studied in healthy subjects and recurrent calcium oxalate stone formers. This treatment resulted in a prompt and significantly increased urinary pH with a duration until 10 a.m. the next day and a reduced risk of calcium oxalate crystallization between 10 p.m. and 10 a.m. In a retrospective study alkaline citrate was given in a single evening dose of 3.75 or 5 gm. to 55 patients with calcium oxalate stone disease and a total dose of 5.0 or 7.5 gm. was administered 2 or 3 times daily in 17 patients. The mean plus or minus standard deviation for duration of treatment was 3.5 +/- 1.7 years. Significantly reduced stone formation was recorded only in those on the evening dose regimen, which was associated with significant improvement of urine composition. Patients who continued to form new stones or who had growth of residual stones despite treatment also had improved urine composition but the calcium excretion and the calcium/citrate quotient remained elevated. In 4 patients with new stone formation calcium phosphate was the major component and calcium excretion was high but the concomitant increased citrate excretion resulted in a calcium/citrate quotient that was only slightly elevated. In patients forming calcium oxalate stones the only abnormality was a high calcium/citrate quotient. Because of favorable biochemical and clinical effects as well as good patient compliance with a single evening dose of alkaline citrate, this regimen appears to be an attractive alternative for long-term prevention of recurrent calcium stone formation.


Plasma and urine glycolate assays for differentiating the hyperoxaluria syndromes.

To differentiate hyperoxaluria syndromes we measured plasma and urine glycolate by a novel high performance liquid chromatographic procedure. Mean glycolate level was 7.9 +/- 2.4 mumol./l. in plasma and 422 +/- 137 mumol./24 hours in urine from 19 control subjects. Renal clearance was about 50% the glomerular filtration rate irrespective of the underlying disease. There was close correlation between glycolate and oxalate in plasma. Plasma glycolate was normal in all but 8 patients who had primary hyperoxaluria 1. Plasma assay detected the disease more efficiently than urine assay. Pyridoxine decreased oxalate biosynthesis in 2 of the 4 patients treated with it and glycolate assay confirmed this behavior. Glycolate excretion was significantly high in 3 of 8 patients of primary hyperoxaluria 1 patients. Idiopathic stone formers had mild increases in glycolate excretion but this was not related with oxalate excretion. Glycolate levels were normal in 5 patients with enteric hyperoxaluria. We conclude that glycolate assay is essential for identifying patients with primary hyperoxaluria 1 and may represent a valuable tool for differentiating hyperoxaluria.


Calcium oxalate crystallization properties in urine with different specific electrical conductivities.

The relationship between the degree of urine dilution and the risk of calcium oxalate crystallization was studied in 32 urine samples collected from stone formers and normal subjects during an 8-hour period between 10 p.m. and 6 a.m., and in 4-hour urine samples collected during 24-hour periods from 6 patients with calcium stone disease. The risk of calcium oxalate crystallization was analyzed in terms of the increase in oxalate concentration required for a standardized precipitation of crystals of calcium oxalate. The degree of urine dilution was determined with a new instrument (urimho) designed for measuring the concentration, in terms of specific electrical conductivity, in urine samples of droplet size. With this device urine concentration can be expressed in urimho values between 1 and 5. There was a good correlation between recordings of specific electrical conductivity performed with the new device and with a conventional conductivity meter. There was a statistically significant positive correlation between urimho values and calcium oxalate crystallization. Calcium oxalate crystallization greater than 1.3 was not observed in any sample with a urimho value of 2 but it was noted in 31% of the samples with urimho values greater than 2. A positive relationship was also recorded between the urine pH and the urimho level, which is noteworthy because there was an inverse relationship between urine pH and calcium oxalate crystallization. A pH greater than 6 was observed in 78% of the samples with a urimho value of 2 but it was noted in only 27% of the samples with urimho readings between 3 and 5. A considerable variation in the response in urinary flow to ingested volumes was recorded. Therefore, monitoring of urine dilution by means of a sample device like the urimho might be of great help for patients with calcium stone disease in an effort to prevent recurrent stone formation by urine dilution, provided a urimho value of less than 3 can be maintained.


Composition of urinary calculi related to urinary tract infection.

The composition of 3,084 urinary calculi was determined using an infrared spectrophotometer. Mixed calcium oxalate-calcium phosphate stones were most frequently implicated. Of the urinary calculi analyzed 199 were associated with urinary tract infection. Escherichia coli was most frequently isolated (43 strains) and urease-producing organisms, such as Proteus mirabilis, were cultured from 40 patients. The core culture of 20 staghorn calculi yielded 15 isolates from 14 stones. There were 13 identical species isolated from the urine and stone specimens of 13 patients (65%), including 7 strains of P. mirabilis. These results suggest that cultures of urine specimens of urolithiasis patients, especially those with staghorn calculi, may help to elucidate the bacteriology of the stones.


Reversing the natural decline in human fertility. An extended clinical trial of oocyte donation to women of advanced reproductive age.

To evaluate the effect of age on pregnancy success rates in functionally agonadal women undergoing oocyte donation. A prospective study of 100 consecutive patients using oocyte donation for the treatment of infertility. Women aged 40 years and above requesting oocyte donation (N = 104) were required to undergo medical, reproductive, and psychological screening. Suitable candidates (n = 65) were matched with an oocyte donor whose cycle was synchronized with that of the potential recipient, prior to the donor's undertaking ovarian hyperstimulation and transvaginal ultrasound-directed follicle aspiration. Outcomes were compared with those of two groups undergoing therapy at the same time: (1) women below 40 years of age undergoing oocyte donation for premature ovarian failure (n = 35) and (2) women 40 years of age and above undergoing standard in vitro fertilization and embryo transfer using their own oocytes (n = 57). Embryo implantation and pregnancy rates. The in vitro fertilization program of the University of Southern California and the California Medical Center, Los Angeles. Improved outcomes were observed with regard to fertilization rates in vitro, number of embryos transferred, embryo implantation rate, clinical pregnancy rates, and ongoing or successfully completed pregnancy rates when women undergoing oocyte donation regardless of age were compared with women 40 years of age and above using their own oocytes. No age-related decline in fertility was demonstrable when oocyte donation was used, with a mean age of 44.3 +/- 3.1 years for those successfully conceiving (range, 40 to 52 years). Perinatal outcomes (n = 27) were generally uncomplicated, with a mean gestational age at delivery of 38.4 +/- 2.1 weeks (range, 34 to 42 weeks), although multiple births occurred in 24.1% of cases. The age-related decline in female fertility may be reversed in couples electing to use donated oocytes from a younger woman, and women of advanced reproductive age may conceive, carry, and give birth to infants with success rates similar to those of their younger counterparts using assisted reproductive methods.


Hospital outbreak of multidrug-resistant Mycobacterium tuberculosis infections. Factors in transmission to staff and HIV-infected patients.

To describe transmission of multidrug-resistant (MDR) Mycobacterium tuberculosis infection among patients and health care workers (HCWs) in a ward and clinic for human immunodeficiency virus (HIV)-infected patients in a hospital, four studies were conducted. Case patients and control patients were persons who had been treated in the HIV ward or clinic, whose clinical course was consistent with tuberculosis and who had at least one positive culture for M tuberculosis between January 1, 1988, and January 31, 1990, resistant to at least isoniazid and rifampin (case patients), or whose isolates were susceptible to all drugs tested (control patients). In the first study, case patients and control patients were compared to identify risk factors for MDR tuberculosis. In the second study, inpatient and outpatient days of MDR tuberculosis case patients were compared to determine whether acid-fast bacillus (AFB) smear-positivity or aerosolized pentamidine use was associated with higher numbers of subsequent MDR tuberculosis cases among exposed patients. In the third study, restriction fragment length polymorphism analysis was performed on available MDR and sensitive M tuberculosis isolates. In the fourth study, skin test conversion rates among HCWs in the HIV ward and clinic were compared with those of HCWs in another ward, and the strength of the associations between skin test conversions among HCWs on the HIV ward and the number of person-days that AFB smear-positive case patients and control patients were on this ward was estimated. Case patients were more likely than control patients to have been exposed on the HIV ward or clinic to an AFB smear-positive case patient (P less than .001). Inpatient and outpatient days of MDR tuberculosis case patients were associated with more subsequent cases of MDR tuberculosis if exposing case patients were smear-positive or if they received aerosolized pentamidine (P less than or equal to .01). Of 13 MDR isolates, all had one of two restriction fragment length polymorphism patterns; 10 sensitive isolates had restriction fragment length polymorphism patterns that were different from each other. The HCW skin test conversion rate was higher on the HIV ward and clinic than on the comparison ward (P less than .01). The risk of occupational acquisition of infection increased in direct proportion to the number of person-days that AFB smear-positive case patients were on the HIV ward (r = .75; P = .005), but did not increase in proportion to the number of person-days that AFB smear-positive control patients were there (r = -.36; P = NS). After isolation measures for AFB smear-positive tuberculosis patients were improved, MDR tuberculosis cases decreased to seven of 214 tuberculosis patients. Nosocomial transmission of MDR M tuberculosis infection to patients and HCWs occurred on the HIV ward and clinic. Infectiousness of MDR tuberculosis case patients was associated with AFB sputum-smear positivity. Case patients with MDR tuberculosis created a greater risk of skin test conversion for HCWs on the HIV ward than drug-susceptible control patients.


Aspirin effects on mortality and morbidity in patients with diabetes mellitus. Early Treatment Diabetic Retinopathy Study report 14. ETDRS Investigators.

This report presents information on the effects of aspirin on mortality, the occurrence of cardiovascular events, and the incidence of kidney disease in the patients enrolled in the Early Treatment Diabetic Retinopathy Study (ETDRS). This multicenter, randomized clinical trial of aspirin vs placebo was sponsored by the National Eye Institute. Patients (N = 3711) were enrolled in 22 clinical centers between April 1980 and July 1985. Men and women between the ages of 18 and 70 years with a clinical diagnosis of diabetes mellitus were eligible. Approximately 30% of all patients were considered to have type I diabetes mellitus, 31% type II, and in 39% type I or II could not be determined definitely. Patients were randomly assigned to aspirin or placebo (two 325-mg tablets once per day). Mortality from all causes was specified as the primary outcome measure for assessing the systemic effects of aspirin. Other outcome variables included cause-specific mortality and cardiovascular events. The estimate of relative risk for total mortality for aspirin-treated patients compared with placebo-treated patients for the entire study period was 0.91 (99% confidence interval, 0.75 to 1.11). Larger differences were noted for the occurrence of fatal and nonfatal myocardial infarction; the estimate of relative risk was 0.83 for the entire follow-up period (99% confidence interval, 0.66 to 1.04). The effects of aspirin on any of the cardiovascular events considered in the ETDRS were not substantially different from the effects observed in other studies that included mainly nondiabetic persons. Furthermore, there was no evidence of harmful effects of aspirin. Aspirin has been recommended previously for persons at risk for cardiovascular disease. The ETDRS results support application of this recommendation to those persons with diabetes at increased risk of cardiovascular disease.


Computer-based interview for screening blood donors for risk of HIV transmission.

To test the ability of a computer-based interview to detect factors related to the risk of the human immunodeficiency virus (HIV) among potential blood donors and to determine donor reactions to the use of the interview. A comparison of the rate of detection of HIV-related factors elicited by a computer interview with that obtained by standard American Red Cross procedures for assessment of donor suitability, including a randomized crossover trial in which the order of the two methods was reversed. Information obtained by the computer was not available to influence the use of blood components for transfusion. The computer interview was administered to donors at an American Red Cross blood donor center and at a mobile blood drive at a hospital. Consecutive sample of 294 male and female blood donors 18 to 75 years of age. Subjects' responses to the computer-based interview as well as responses to the standard Red Cross written questionnaires and face-to-face interviews were used for donor assessment. The interview took an average of 8 minutes to complete. From among 272 donors who provided complete data, the computer identified 12 donors who reported either behaviors associated with a risk of HIV acquisition or symptoms compatible with the acquired immunodeficiency syndrome; none of these donors had been so identified either by routine written questionnaires or by face-to-face interviews used to screen potential blood donors. Only one of the 12 identified donors used the confidential unit exclusion procedure to prevent use of his donated unit. The rate of elicitation of HIV-related factors by the computer interview was 12 (4.4%) of 272 (95% confidence interval [CI], 2.3% to 7.6%), compared with two (0.13%) of 1536 (95% confidence upper bound, 0.28%) using the standard Red Cross procedure (P less than .0001). Tests for antibodies to HIV were negative in blood samples from all of the 272 subjects studied. The subjects enjoyed the computer interview and judged it to be more private than the standard donor assessment method. They also predicted that donors would be more honest with the computer interview than with a human interviewer. Computer-based screening elicits more HIV-related factors in the health histories of blood donors than do the standard questionnaire and interviewing methods currently in use. Computer-based screening is also acceptable to blood donors.


Prescription drug diversion control and medical practice.

Concern about the role of prescription drug diversion in drug abuse has led to demands for more stringent regulation and for better ways to detect prescription drug diversion. Advances in technology now allow point-of-sale computer systems to report prescriptions filled by pharmacies to state agencies rapidly and possibly more economically. However, the advantages of more comprehensive control systems must be balanced against their possible effects on medical practice and patient care. Our limited knowledge about prescription drug diversion and the impact of diversion control systems on medical practice is summarized. Needed research is outlined together with the components of a diversion control program that balances reducing drug diversion with minimizing adverse effects on medical practice and patient care. We stress the need for broadly defined practice parameters and peer review by medical experts thoroughly familiar with the complexities of medical practice.


Use of a novel technique of cutaneous lavage for diagnosis of Lyme disease associated with erythema migrans.

Determining the microbial cause of cellulitis is often difficult. In this study, a novel two-needle lavage technique was used to culture Borrelia burgdorferi from the skin of suspected erythema migrans lesions. The yield of lavage cultures for B burgdorferi was compared with that of a 2-mm skin biopsy sample. A Lyme disease diagnostic center located in an area in which Lyme disease is epidemic. Forty-five patients with suspected erythema migrans who had not been treated with antimicrobial agents. Cutaneous lavage of the advancing edge of a suspected primary erythema migrans lesion was done for all 45 participants, 33 of whom also had a skin biopsy of the same lesion at an identical (14) or an adjacent (19) site. Growth of B burgdorferi in in vitro culture. Lavage fluid cultures grew B burgdorferi in 13 (29%) of the 45 cases (95% confidence interval [CI], 16% to 44%). Among the 33 cases in which both lavage and skin biopsy cultures were done, the yield of lavage culture was less than that of biopsy culture (P less than .09, 12/33 vs 20/33). If contaminated cultures are excluded, this difference is significant (P less than .05, 12/30 vs 20/27). Cutaneous lavage is a new diagnostic technique for recovery of B burgdorferi from erythema migrans lesions that has potential applicability to other types of cutaneous infections.


Role of thymectomy in myasthenia gravis.

Thirteen patients with myasthenia gravis underwent total thymectomy between January, 1988 and December, 1991. The duration of symptoms prior to surgery varied from 2 months to 20 years. In a follow-up ranging from 2 months to 4 years, 11 patients showed a significant improvement with either complete discontinuation of medication or a marked reduction in doses. One patient with a small benign thymoma showed some improvement but subsequently required stepping up of anticholinesterase medication and addition of steroids and immunosuppressants; another patient with atrophic thymic tissue had complete remission after thymectomy but developed myasthenic symptoms six months later requiring medication again. Thymectomy is recommended for all patients with generalised myasthenia gravis with or without thymoma regardless of the duration of disease unless the patient is a very high risk candidate for surgery. It is not recommended for isolated ocular myasthenia gravis.


Cholecystectomy in acute cholecystitis.

Of 130 patients admitted with acute cholecystitis, 100 were selected for a prospective study comparing the risks and benefits of early cholecystectomy versus initial conservative management followed by elective surgery. Comparative evaluation was carried out regarding operative difficulties and mishaps, postoperative complications, duration of hospitalization and compliance for surgery. Early cholecystectomy has advantage in terms of quick definitive treatment, completion of therapy in one hospital admission and salvage from serious complications of acute cholecystitis. Operative difficulties and mishaps and postoperative complications are comparable with delayed surgery. It obviates the danger of non-compliance by not reporting on the scheduled appointment. But it should be undertaken by an experienced surgeon and antibiotics should be administered prophylactically and following surgery to decrease the chances of septic complications. With these provisions it can be recommended as a treatment of choice for acute cholecystitis if the diagnosis can be established with confidence.


Psychiatric morbidity among overseas students.

As immigration for higher education is becoming more common now a days, the adjustment of overseas students to the host country is receiving more attention. This paper describes the results of a study which examined the prevalence and pattern of psychological disturbances among overseas and British students studying at Edinburgh University. The practical implications of these findings and suggestions for future research are discussed.


Prevalence of iron deficiency anaemia in children of the urban slums of Karachi.

A preliminary baseline survey was conducted to estimate the prevalence of anaemia in a group of 391 children aged 6-60 months, randomly selected from three urban slums of Karachi. Haemoglobin and the red cell indices including haematocrit, MCV, MCH, MCHC, RBC and red cell distribution width (RDW) were estimated for each of the selected children. Ferritin estimation was done on 354 (91%) children to assess the iron storage status. According to WHO criteria, the accepted cut-off point for anaemia screening in children is set at 11 gm/dl, 70 fl and 20 pg for haemoglobin, MCV and MCH respectively. Following these criteria, 118 (30%) children were classified as normals (Hg = greater than 11 gm/dl) and 273 (70%) as anaemic (Hg = less than 11 gm/dl). Of the 354 ferritin estimations, 225 (64%) children had ferritin levels lower than normal (less than 11 ng/ml) and 128 (36%) had ferritin levels within normal limit (11-120 ng/ml). From this group, a total of 61% (214/354) children were classified as microcytic hypochromic (MIH) and 11% (39/354) of which had normal ferritin levels suggesting the presence of thalassemia minor trait. The overall results obtained indicate that iron deficiency anaemia is highly prevalent among these children.


IgM and IgG antibodies specific to rubella in child bearing women.

Three hundred fifty five pregnant women were tested for IgM and IgG type of antibodies by Enzyme Immuno Assay (EIA). Sero-positivity for IgM and IgG antibodies were 13% and 29% respectively. Of 212 pregnant women with abortion, 39 (18%) and 80 (38%) were sero-positive and of 143 pregnant women with normal reproductive performance, 7 (5%) and 23 (16%) were positive for IgM and IgG respectively. Premarital screening and vaccination of Sero-negative girls is recommended to reduce morbidity and mortality related to rubella virus.


[Bacteriological evaluations of combination therapies with minocycline and beta-lactams for methicillin-resistant Staphylococcus aureus. I. Cefotiam plus minocycline].

Since methicillin-resistant Staphylococcus aureus (MRSA) is resistant to multiple antibiotics, only a limited number of antibacterial agents shows efficacy against this bacteria. Therefore, combination therapy is often attempted for MRSA infections. Most of the MRSA strains recently isolated, however, have been found to show very high resistance, and some of the antibiotics which had previously been effective have been failing to produce good responses in increasing numbers of patients. Thus, the drugs used for combination therapy in MRSA infections need to be reevaluated. We assessed the bacteriological efficacy of cefotiam (CTM) plus minocycline (MINO) therapy against MRSA in an in vitro system (CTM shows relatively strong antibacterial activities against MRSA with moderate resistance, and MINO shows strong antibacterial activities against highly resistant MRSA. 1. Against MINO-susceptible MRSA strains, CTM + MINO demonstrated potent antibacterial activities at MINO concentrations of MIC or sub-MIC levels, irrespective of the MIC of CTM against MRSA strains being tested. 2. Against MINO-resistant MRSA strains (strains for which MICs of MINO exceeded the upper limit of the clinically expected plasma MINO level), CTM + MINO showed no significant antibacterial activity. These results suggested that the effect of this combination was dependent on the antibacterial activity of MINO. Therefore, the usefulness of this combination in patients with MRSA infections can be predicted based on susceptibilities of involved strains to MINO. 3. The potent antibacterial effect of this combination against MINO-susceptible MRSA strains was considered to be the result of damage to the cellular membrane by MINO and the subsequent antibiotic effect of CTM.(ABSTRACT TRUNCATED AT 250 WORDS)


[Bacteriological evaluations of combination therapies with minocycline and beta-lactams for methicillin-resistant Staphylococcus aureus. II. cefuzonam plus minocycline].

We performed an in vitro assessment of the antibacterial activity of therapy with cefuzonam (CZON) plus minocycline (MINO) against methicillin-resistant Staphylococcus aures (MRSA) infections. 1. Studies using MINO-susceptible and MINO-resistant MRSA strains suggested that the antibacterial activity of CZON + MINO was dependent on the antibiotic action of MINO, similarly to the case with cefotiam (CTM) + MINO. 2. The antibacterial activity (including the FIC index) of this combination was slightly inferior to that of CTM + MINO. However, the time course of antibacterial efficacy of CZON + MINO in MRSA pretreated with MINO was comparable to that of CTM + MINO. 3. CZON + MINO appeared to be a very useful combination in patients with mixed infections due to MRSA and Gram-negative bacteria.


[Cefepime (diHCl/L-arginine blend): intravenous continuous infusion and/or single dose subcutaneous toxicity study in rats and dogs].

To investigate single dose toxicity of cefepime (CFPM diHCl/L-arginine blend), the test drug was administered to rats [Crj: CD (SD)] of both sexes at dose levels of 500, 1,000 and 2,000 mg/kg using intravenous continuous infusion or subcutaneous injection, and to male beagle dogs at 1,000 and 2,000 mg/kg using intravenous continuous infusion. As the control, two additional groups of each animals were given either saline or L-arginine alone which was used in the test formulation to adjust pH values of CFPM diHCl solutions. The obtained results are summarized as follows: 1. Rats dosed with 2,000 mg/kg CFPM through intravenous continuous infusion showed slightly decreased spontaneous physical activity. One male rat dosed with L-arginine alone via continuous infusion also showed slightly decreased activity. Slight to severe inflammatory reactions at injection sites including sloughing of the tail were prominent at doses of 1,000 or 2,000 mg/kg of CFPM, or L-arginine alone. Average body weights of rats in the test groups of either sex were comparable to the controls in all of the dose groups of the same sex during the 14-day test period. 2. Rats receiving 2,000 mg/kg CFPM in single subcutaneous injection showed slightly diminished activities. Slight to moderate reactions occurred around the injection site (viz., hardening, depilation, scab-formation and necrosis) in rats injected any of the 3 doses of CFPM. Though body weight gains were slightly retarded in male rats receiving 2,000 mg/kg CFPM during the last half of the observation period, such weight gain retardation was not observed in rats of other dose groups.(ABSTRACT TRUNCATED AT 250 WORDS)


[Cefepime (BMY-28142 diHCl/L-arginine blend): one-month repeated dose subcutaneous toxicity study in rats].

In order to investigate the toxicity of cefepime (CFPM, BMY-28142 diHCl/L-arginine blend upon repeated subcutaneous dosing), the test article was administered to Crj:CD(SD) rats of both sexes at daily dose levels of 150 (low dose), 500 (intermediate dose) and 1,500 (high dose) mg/kg/day by subcutaneous route for 28 days. Two additional groups of rats were given either saline (negative control) or L-arginine (vehicle control). Doses were equally divided and administered twice each day with an interval of approximately 5 hours between the 2 doses of a same day. A half of rats in negative control and high dose groups were retained for examination during one-month recovery period. The results obtained are summarized as follows: 1. Upon general observations, it was found that drug-related changes were restricted to the injection sites. Depilation and scab-formation of the injection sites were noted in high dose rats of both sexes and intermediate dose females. No deaths occurred during the study. 2. Slightly depressed body weight gains were observed for high dose males during the latter part of the dosing period. 3. Slightly lower food consumptions were noted for intermediate and high dose males at Week 1. 4. Slightly higher water consumptions were generally detected for high dose rats during the dosing period. 5. Hematological examinations revealed that a slight decrease in the average value of relative lymphocyte counts and a slight increase in the average value of relative segmented neutrophil counts were evident for high dose males. These findings might be attributable to the inflammatory reactions at the injection sites.(ABSTRACT TRUNCATED AT 250 WORDS)


[Reproductive and developmental toxicity studies on cefepime dihydrochloride administered subcutaneously to rats during the premating, gestation and lactation periods].

Cefepime dihydrochloride (CFPM) was administered subcutaneously daily at doses of 0, 150, 500 and 1,000 mg/kg for 63 days prior to mating and during mating to male Crj: CD (SD) rats and for 14 days prior to mating and during mating, as well as periods of gestation and lactation to female SD rats. Saline and L-arginine hydrochloride (L-arginine) were used as control articles. Daily doses of test and control articles were equally divided and administered twice a day (b.i.d.). The results obtained are summarized as follows: 1. Soft stool was observed for both male and female F0 rats at CFPM 1,000 mg/kg at the first week of administration period. Further, depilation of injection sites was found in 7 males and 12 females at the same dose level. 2. Body weight gains were suppressed in male F0 rats from Day 28 to 63 of administration period at CFPM 1,000 mg/kg. Moreover, food consumption was reduced in F0 female rats during the first week of administration period at all dose levels of CFPM. 3. CFPM failed to affect the reproductive performance in both male and female F0 rats. 4. Kidney weights were increased in both male and female F0 rats and adrenal weights were augmented in male F0 rats at CFPM 1,000 mg/kg. On the other hand, cecal enlargement were observed for F0 dams treated with CFPM. However, these changes were not considered to be unique to this drug, because they have been described with most antibiotics in this species and appears to be results of modifications in gut flora. 5. Prenatal developments in F1 fetuses were not affected by CFPM. 6. CFPM failed to affect delivery status of F0 dams or survival and lactation indices in F1 pups. 7. CFPM did not affect postnatal differentiations, developmental behaviors, learning ability and memory, spontaneous motor activity or emotionality in F1 rats. 8. Body weight gains and food consumption in both male and female F1 rats were not affected by CFPM. 9. CFPM did not alter the organ weights in both male and female F1 rats. 10. There were no significant differences between drug treated animals and controls regarding the reproductive performance and delivery status of F1 rats. 11. Influences on survival indices, body weights and organ weights were not apparently observed for F2 pups even at CFPM 1,000 mg/kg. Based on the reproductive and developmental indices, the no-effect dose level of CFPM under the present experimental condition was estimated to be 1,000 mg/kg/day against dams (F0) and their offspring (F1).


[General pharmacology of cefepime].

General pharmacological properties of cefepime (CFPM), a new injectable semisynthetic cephalosporin and its metabolite N-methylpyrrolidine-N-oxide (NMP-N-oxide) were studied in laboratory animals. The results obtained are summarized as follows: 1. CFPM reduced spontaneous locomotor activity but potentiate the anesthesia at the highest dose in mice. Furthermore, significant hypothermia and analgesia were observed at the same dose in mice. No effects were found on the other CNS function in mice and rats or on EEG activities in rabbits. 2. Muscle relaxant activity was not observed in mice treated with CFPM even at the highest dose. 3. CFPM had no effect on the intestinal smooth muscle and did not show any antagonism against some smooth muscle contracting drugs. 4. The respiration, blood pressure, heart rate and ECG were affected by CFPM. Those changes, however, might have been principally caused by L-arginine blended with CFPM product. 5. No effect of CFPM on the intestinal movement or gastric secretion was found even at the highest dose of CFPM. 6. The pH neutralizer L-arginine caused alterations in the renal function and electrolyte metabolism but CFPM did not. 7. Whole blood clotting time tended to be lengthened by CFPM at the highest concentration but this effect seemed to have been caused by L-arginine. Other parameters of the coagulation system or red blood cell resistance were not affected by CFPM. 8. NMP-N-oxide, a metabolite of CFPM, had almost no effect on any of the tested parameters except for its slight effect on the circulatory system. These findings indicate that CFPM has scarcely any pharmacological properties which might be leading to severe adverse reactions in clinical use.


[Clinical efficacy of ceftriaxone when administered once daily for respiratory tract infections in patients with advanced ages].

Ceftriaxone (CTRX), a new third generation cephalosporin, was investigated upon once daily administration for its clinical efficacy and safety on respiratory tract infections in patients with advanced ages. The results are summarized as follows: 1. Clinical responses to CTRX of 48 cases of advanced age patients with respiratory tract infections were good with an efficacy rate of 89.6%. 2. Adverse reactions to CTRX were mainly exanthema in 7 cases (14.6%). 3. Serum levels of CTRX were determined in 4 cases after intravenous drip infusion of 2 g CTRX. Serum levels were analyzed by one-compartment model. There was no evidence of accumulation of CTRX in the patients with advanced ages.


[Therapeutic effects of meropenem against severe infections in patients with hematopoietic disorders. Hanshin Study Group of Hematopoietic Disorders and Infection].

The efficacy and the safety of meropenem (MEPM), a newly developed carbapenem antibiotic, were investigated in 150 patients with severe infections complicated with hematopoietic disorders. 1. Clinical responses in 132 patients who were evaluable for effectiveness were excellent in 33 patients, good in 45, fair in 10 and poor in 44, with an efficacy rate of 59.1%. 2. The efficacy rate in patients who had previously been treated with the other antibiotics was 51.2%, while that in patients who had not been thus treated was 62.9%. 3. The efficacy rate in patients whose neutrophil counts increased during the therapy with MEPM was higher than that in patients whose neutrophil counts did not increase. The efficacy rate in patients whose neutrophil counts during the therapy were below 100/mm3 was 48.1%. 4. Out of 150 cases, side effects were observed in 4 patients, 3 with eruption and 1 with jaundice. Abnormalities in laboratory test results on liver functions were noted in 8 patients. These results indicate that MEPM is an effective and safe antibiotic for the treatment of severe infections in patients with hematopoietic disorders.


[Pharmacokinetic and clinical studies with meropenem in the pediatric field. Pediatric Study Group of Meropenem].

Pharmacokinetic and clinical evaluations in pediatrics were made on meropenem (SM-7338, MEPM), a new parenteral dehydropeptidase-1 stable carbapenem used without any inhibitors, at 33 medical institutions. The results are summarized as follows. 1. Pharmacokinetic studies. MEPM at a dose of 10, 20, or 40 mg/kg was administered to 53 children by 30-minute drip infusion. Peak plasma concentrations (Cmax's) and plasma half-lives (T1/2's) of these doses were 28.5, 47.2 and 130.0 micrograms/ml, and 0.80, 0.93 and 0.94 hours, respectively. A clear dose response was observed in Cmax's and T1/2 values were quite similar to those observed in adults. In the first 6 hours after administration, 54.4 to 68.1% of the administered drug was recovered in urine. The cerebrospinal fluid (CSF) levels of MEPM in patients with purulent meningitis were 0.13 microgram/ml at a dose of 6 mg/kg, and 0.64 to 4.22 micrograms/ml at a dose of 29 to 44 mg/kg within day 4 of onset. The penetration rate of MEPM showed an intermediate value among those for other cephalosporin antibiotics. 2. Clinical study. Clinical efficacies of MEPM were evaluated in 389 cases. The most common doses used were 10 to 20 mg/kg/once, 2 to 3 times a day. The maximum dose was 173 mg/kg/day q.i.d. MEPM gave "excellent" or "good" responses in 242 (97.6%) out of 248 cases in which causative organisms were documented and in 134 (95.0%) out of 141 cases in which causative organisms were not identified. Clinical efficacy rates were 100% in 11 patients with purulent meningitis, 85.7% in 7 with septicemia, 98.8% in 173 with pneumonia, and 100% in 65 with UTI. Bacteriologically, 260 strains (96.7%) out of 269 strains were eradicated by MEPM treatment. Eradication rates were 89.2% for Staphylococcus aureus (37 strains) and 100% for Streptococcus pneumoniae (35 strains). The overall eradication rate for Gram-positive bacteria was 94.6%. Among Gram-negative bacteria, 98.3% out of 172 strains were eradicated. The eradication rate of Haemophilus influenzae (73 strains) was 98.6% and Pseudomonas aeruginosa (11 strains) was 90.9%, and all of Branhamella catarrhalis (15 strains), Escherichia coli (42 strains), and Klebsiella pneumoniae (6 strains) were eradicated. Out of 84 cases for which previous antibiotic therapies of 3 days or longer were not successful, MEPM gave "excellent" or "good" responses in 77 cases (91.7%) and excellent bacteriological responses (95.7%).(ABSTRACT TRUNCATED AT 400 WORDS)


[Clinical and pharmacokinetic evaluation of meropenem and its effect on fecal flora in children].

Forty-five children were treated with meropenem (MEPM) and the clinical efficacy and side effects were evaluated. The ages of the patients ranged from 1 month to 9 years and their body weights from 5.2 to 25 kg. Doses given were 17.2-45.5 mg/kg every 6 to 8 hours for 2 to 24.5 days. Those patients who responded to the MEPM treatment included 15 children with pneumonia, 7 with pharyngitis, 3 with cervical lymphadenitis, 3 with cellulitis, 10 with urinary tract infections and 4 with other infections. Among 42 children, the results were excellent in 29, good in 12 and fair in 1. The drug was well tolerated, although slightly elevated serum concentrations of transaminases occurred in 5 patients, eosinophilia in 2 patients, and neutropenia in 1 patient among 45 patients examined. The pharmacokinetic studies on MEPM were done in 6 patients. Their ages ranged from 2 to 9 years and body weights from 14.5 to 23.2 kg. In 4 patients, plasma concentrations at the end of 30 minutes drip infusion of 20 mg/kg were 29.28 +/- 10.29 micrograms/ml and those 3 hours later were 0.49 +/- 0.26 micrograms/ml. Serum elimination half-lives of the drug were 0.66 +/- 0.12 hours in these patients. Excretion rates of this drug into urine in the first 6 hours after initiation of drug administration were 53 and 40% in 2 of these patients. In 2 patients with 35 and 44 mg/kg of drug administration, plasma concentrations were higher than those given 20 mg/kg of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)


[Clinical pharmacology and efficacy of meropenem].

We studied a newly developed carbapenem, meropenem (MEPM), and obtained the following results. 1. Pharmacokinetics of MEPM in pediatrics was examined in 3 patients. MEPM was injected intravenously at a dose of 16-22 mg/kg by drip infusion for 30 minutes, and its concentrations in serum and urine were determined using bioassay. The average peak value of serum levels of MEPM was 38.4 micrograms/ml and T1/2 beta of MEPM was 1.26 hours. The urinary recovery rate for the first 6 hours after administration was 65.6%. 2. Clinical evaluations of MEPM in pediatrics were done in 14 patients with ages ranging, 1 month to 14 years, with various bacterial infections. Excellent or good clinical responses were observed in all patients, and bacteriological eradication were obtained in 7 out of 8 cases. No serious side effects were observed in any cases, but 2 showed mild and transient GOT, GPT elevations.


[Clinical evaluation of meropenem in children].

Meropenem (MEPM) was evaluated for its efficacy and safety. The following results were obtained. MEPM was given to 12 patients with infections: 5 with pneumonia, 1 with bacterial meningitis, 2 with pharyngitis, 4 with skin and soft tissue infections. Therapeutic responses were "excellent" in 5, "good" in 4 and "fair" in 3, with an efficacy rate of 75%. Adverse reactions were not noted. No abnormalities were shown in laboratory data. It has been concluded that MEPM is a useful drug for the treatment of bacterial infections in children.


[Clinical evaluation of meropenem in the pediatric field].

We studied the clinical efficacy of meropenem (SM-7338, MEPM), a new parenteral carbapenem beta-lactam antibiotic, in pediatric field. Thirteen patients with 2 months to 8 years and 8 months of ages, with acute infectious diseases were administered with doses at 39.3 to 76.7 mg/kg/day of MEPM intravenously. The diagnoses consisted of 7 respiratory tract infections, 1 sepsis, 2 orbital cellulitis, 1 parotid abscess, 1 lymphadenitis and 1 pyoderma. The clinical efficacy rate was 84.6% (11/13), and the bacteriological eradication rate was 71.4% (5/7). Clinical laboratory examinations revealed 1 patient with eosinophilia and another with anemia. No other side effects attributable to this drug were observed. It appears that MEPM is a useful antibiotic for moderate to severe acute bacterial infections in children.


[Bacteriological and clinical studies on meropenem in the pediatric field].

Bacteriological and clinical studies have been performed on meropenem (MEPM, SM-7338), a newly developed carbapenem antibiotic, in the pediatric field. 1. Antibacterial activities of MEPM against 24 clinical isolates were determined. MEPM showed excellent activity against Gram-positive bacteria including Staphylococcus aureus and Gram-negative bacteria, especially Escherichia coli and Branhamella catarrhalis. Against Haemophilus influenzae, MEPM had a higher activity than imipenem and flomoxef, but had a lower activity than piperacillin and cefoperazone. 2. Clinical efficacies of MEPM were evaluated in 32 cases with bacterial infections. A poor efficacy was observed in 1 patient with phlegmon but excellent or good efficacies were obtained in other 31 patients with tonsillitis (1), pneumonia (17), UTI (12), or SSSS (1). The overall efficacy rate was 96.9%. All strains except 1 of S. aureus were eradicated by the administration of MEPM, and a high eradication rate of 95.8% (23 out of 24 strains) was obtained. 3. No side effects were observed in 35 evaluated cases. As abnormal laboratory test results, elevated GOT, elevated GPT, eosinophilia and neutropenia were noted in 4, 4, 4 and 2 patients, respectively. 4. Influences on blood coagulation parameters were studied. PIVKA II was elevated upon administration of MEPM in some cases, but no changes in ATT, TT, HPT or Fbg were observed during the treatment. Based on the above results, it has been concluded that MEPM is a safe and effective drug to use in the treatment of pediatric infections. The usual recommended dosage and administration should be 10 to 20 mg/kg of MEPM at a time, using intravenous drip infusion, 3 times a day.


[Favorable prognoses in 24 adult patients with acute leukemia, surviving over five years since 1985].

Since 1985 we have experienced 24 leukemia cases with long-term survival, who were treated with one of three types of postremission therapy. Of them, 20 patients were physically fit for ordinary work and returned to their work as workers or housewives during long-term follow-up period. Two housewives gave birth. We have devised three types of postremission therapy; 1) multidrug combination therapy with gradually longer intermissions (January 1980-March 1983); 2) controlled randomized clinical trial by the Japanese Foundation for the Multidisciplinary Treatment of Cancer, April 1983-March 1985-March 1988). In a group who underwent multidrug combination therapy without prednisolone, 12 of 20 patients who achieved complete remission have shown continued complete remission, as of November 1991, including seven 5-year survivors. These results indicate that improvement of postremission therapy makes it possible for adult patients with acute leukemia to survive 5 years or longer.


[Philadelphia chromosome (Ph1) positive acute myelomonocytic leukemia with esophageal cancer: a case report].

A 62-year old male was admitted to our hospital because of fever and dysphagia on November 14, 1987. The peripheral leukocyte count was 174,400/microliters with 93% blasts and bone marrow aspiration showed that 90.4% of nucleated cells were blasts positive for both myeloperoxidase and alpha-naphthylbutyrate esterase. Chromosome analysis revealed a karyotype of 45XY, 9q+, 16q+, -20 and 22q-. Esophageal X-ray and endoscopy showed abnormalities. Esophageal biopsy revealed squamous cell carcinoma. He was diagnosed as having Ph1 positive acute myelomonocytic leukemia (AMMoL, M4) and esophageal cancer. He was treated with BHAC-DMP and intermediate-dose ara-C therapy for leukemia and a complete remission was obtained by March 25, 1988. As treatment for esophageal cancer, radiation therapy (total 4,200 cGy) was given and followed by chemotherapy with CDDP and 5-FU. However he died on April 8, 1988. Autopsy findings showed disseminated invasion of esophageal cancer. Ph1 positive AMMoL associated with esophageal cancer is extremely rare.


[Sick sinus syndrome in a patient with myeloma-associated amyloidosis].

A 62-year-old woman was admitted with general malaise and anorexia in September, 1988. Multiple myeloma (IgA-lambda, Stage IIIb) was diagnosed, and amyloidosis was also diagnosed by abdominal fat aspiration biopsy. A partial remission was achieved by MEVP combination chemotherapy, and she was discharged in December, 1988. She was readmitted because of dizziness and palpitation in April, 1989. A diagnosis of sick sinus syndrome was made, and a VVI permanent pacemaker (PPM) was implanted. She was able to walk to our outpatient clinic for 10 months after the PPM implantation. However, right hemiplegia and aphasia were recognized on April 19, 1990. CT scans revealed low density in the areas of the left anterior and middle cerebral artery. The symptoms of congestive heart failure worsened progressively, and the patient, who had been confined to bed, died on March 5, 1991. She was the fifth myeloma-associated amyloidosis patient who received a PPM implantation. Her survival time was one year and ten months, and was the longest among a small number of reported cases with PPM implantation.


[Three familial patients with chronic acquired pure red cell aplasia].

It has not been reported that chronic acquired pure red cell aplasia (PRCA) occurs among family members. The authors report his at familial patients with chronic acquired PRCA, a 23-year-old male, a 54-old uncle and a 20-year-old male cousin. They had no complication sor thymoma, and hematological findings were compatible with typical chronic acquired PRCA. In the 23-year-old male, the autologous BFU-E number was suppressed by the addition of pretreatment serum, and in the his uncle, the autologous CFU-E number was suppressed by the addition of IgG fraction of plasma. In these cases, the development of PRCA was considered to be based on the autoimmune mechanism due to by the presence of serum antibodies. This suggests the possibility that genetically inherited susceptibility may also be an important factor causing chronic acquired PRCA.


[Secondary sideroblastic anemia caused by long term administration of anti-tuberculous agents including isoniazid].

A 54 year-old man, who had been treated for several years with isoniazid, was transferred to our hospital because of intractable pulmonary tuberculosis. He was given several anti-tuberculous agents including INH, CS and/or PZA for a long period of time without improvement of the pulmonary tuberculosis. After 7 years' treatment with INH, hypochromic microcytic anemia developed. Parenteral administration of iron preparation failed to improve the anemia. The bone marrow findings revealed erythroid hyperplasia and a few erythroblasts showed megaloblastic change. The bone marrow iron staining revealed increased sideroblasts of which 88% were ringed-form. INH was then discontinued and pyridoxal phosphate was administered with rapid complete improvement of the anemia. INH is well known as a causative agent for acquired secondary sideroblastic anemia, however only one case of INH-induced sideroblastic anemia has been reported in Japan. This is the second reported Japanese case of INH-induced secondary sideroblastic anemia, which appears to be a very rare condition because of genetically determined rapid acetylation of INH in Japanese.


[Successful treatment of prolonged anemia after major ABO incompatible bone marrow transplantation for a case of myelodysplastic syndrome with recombinant erythropoietin].

A delay in red cell recovery after ABO-incompatible bone marrow transplantation (BMT) is often observed. The authors experienced a case of prolonged anemia after a major ABO incompatible BMT for myelodysplastic syndrome which was successfully treated with recombinant human erythropoietin (Epo). Effects of Epo were confirmed by the recurrence of anemia after withdrawal of Epo as well as the rapid reincrease in reticulocytes on readministration. The patient received a dose of Epo which was similar to the amount used for renal anemia, however serum concentration of Epo after administration exceeded endogenous Epo levels. Epo may have a beneficial role in the treatment of prolonged anemia after BMT.


[An epidemiological study of methicillin-resistant Staphylococcus aureus (MRSA) isolated from medical staffs, inpatients and hospital environments at our hospital].

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important microorganisms which is causative of the nosocomial infections. Recently the incidence of isolation of MRSA is increasing from year to year in Japan. Especially MRSA isolated from inpatients are much higher than from outpatients. Therefore we have done epidemiological studies about MRSA isolated from medical staffs, inpatients and hospital environments in our hospital. Thereafter we examined phage typing and coagulase typing of those MRSA. MRSA were isolated more frequently from anterior nares of inpatients in compare with doctors and nurses. MRSA were isolated more frequently from the environments of MRSA carriers. Coagulase type II and phage type N.T. (not typable) were dominant type of MRSA in our hospital (69% and 61%). Our studies have revealed that the isolation frequency of MRSA is very high in our hospital. It seems to suggest that inpatients who are carrying MRSA are spreading MRSA out hospital environments and medical staffs.


[An attempt to control nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection].

A strain of Methicillin-Resistant Staphylococcus aureus (MRSA) was first isolated in our hospital in March 1986. Since then, MRSA has become a difficult pathogen and a cause of sepsis, bacterial endocarditis, and pneumonia in 1988. Rigorous hospital-wide control measures have been planned. The major control measures, based on the various investigations reported, consist of the following three points; improvement of environmental control, reinforcement of handwashing practices during care and control usage of antibiotics. The frequency of isolation of MRSA among the S. aureus isolates was 43.3% in 1988 and this was further reduced to 31.7% in 1990. The total number of MRSA isolates from decubitus, bile, and blood samples have also declined. This decline resulted in a reduction of cases of severe MRSA infection. As yet, MRSA strain are still isolated on incubation. There may be a limit to complete control by measures in a single hospital. It is desired that regional measures and national consensus on nosocomial infection be established.


[The structure and function of the mecA gene in methicillin-resistant Staphylococcus aureus].

Penicillin binding protein (PBP) 2' is the most important mechanism of the resistance to beta-lactams in methicillin-resistant Staphylococcus aureus (MRSA). And the mecA gene is the coding gene of PBP2', and located in the SmaI fragment G of the chromosome map by Pattle P.A.,. A part of the structure of mecA is similar to that of the penicillinase gene. The resistance of MRSA to beta-lactams were influenced by the presence of penicillinase plasmid and the alternation of femA gene.


[Characterization of femA gene product by penicillin-binding protein assay].

To characterize the femA gene product by penicillin-binding protein (PBP) assay, cloned femA sequence was introduced into methicillin-sensitive femA mutant Staphylococcus aureus BB308 and into Escherichia coli JM109. Overproduced femA gene product was detected in the membrane fraction of the S. aureus and E. coli transformants by SDS-PAGE and Coomassie-blue staining, but no penicillin-binding activity was observed in the femA gene product. Both BB308 and its transformant produced PBP 2' and other PBPs, as much as clinically isolated methicillin-resistant S. aureus strains. The degree of restoration of methicillin resistance varied depending on the introduced femA sequences derived from six different S. aureus strains. A hypothetical mechanism of femA to affect beta-lactam resistance in S. aureus is discussed.


[The beta-lactamase activity in methicillin-resistant Staphylococcus aureus--a comparison of the beta-lactamase from a methicillin-resistant and from a methicillin-sensitive strain of Staphylococcus aureus].

Strains of Methicillin-resistant Staphylococcus aureus (MRSA) are more frequently beta-lactamase-negative than those of Methicillin-susceptible S. aureus (MSSA). In the strains of MRSA, the beta-lactamase activity tends to be inversely related to the MIC's of Methicillin. Such a marked tendency has been observed in recent years.


[Vancomycin and arbekacin, drugs of treatment for MRSA infections].

In Japan, the Ministry of Health and Welfare has permitted recently that vancomycin is given parenterally. Therefore, this drug will be useful for the treatment for MRSA infections. Arbekacin, a newly developed aminoglycoside antibiotic, showed more active than vancomycin to MRSA in vitro. Therefore this drug will be also useful for the treatment for MRSA infections. Combined activity of arbekacin and vancomycin against 27 MRSA strains was evaluated by checkerboard technique. No synergistic effects were detected against these strains. Antagonistic effects were observed against 2 strains. "Vancomycin-arbekacin combined therapy" should be done, therefore, to restricted cases.


[Effective single and combined chemotherapeutic regimens as regards to antibiotic resistance patterns of methicillin-resistant Staphylococcus aureus (MRSA) in Japan].

The incidence of gentamicin-resistant MRSA (GMr-MRSA) has been gradually increasing since early 1980's in Japan. The GMr-MRSA mainly belongs to Group-I phage type and to Group-IV coagulase type. It is rather difficult to induce methicillin-resistance in the GMr-MRSA in the presence of beta-lactam antibiotics. Since late 1980's tobramycin-resistant MRSA (TOBr-MRSA) has been increasing rapidly in place of GMr-MRSA. The TOBr-MRSA mostly belongs to Group III phage type and Group II coagulase type. It rapidly acquires resistance to methicillin and becomes highly resistant to many other related antibiotics as evidenced by statistics in 1980's in Japan. A combination chemotherapy with imipenem/cilastatin and 1st or 2nd generation cephem, or minocycline plus cephem is considered to be effective for MRSA infections. However, a combination chemotherapy with arbekacin (ABK), or vancomycin (VCM) plus beta-lactam antibiotic is recommended especially for the treatment of respiratory tract infections.


[MRSA respiratory tract infection].

Sputum isolates of MRSA have been on the increase, recently. Preventive measures against MRSA nosocomial infections have become important in Japanese hospitals. Clinical study was performed on 29 patients from whom MRSA was isolated more than 10(7) cfu/ml using the quantitative sputum culture method. All had a history of admission, therefore nosocomial infections caused by MRSA could very often occur. MRSA was determined as a causative organism in 3 on the basis of symptoms, laboratory data, chest X-rays, and effect of antimicrobial agents. These three patients improved by a single or combined administration of minocycline, arbekacin and/or fosfomycin. In 15 patients, MRSA was frequently isolated, but was thought to be colonized. In 3 patients, MRSA was not isolated without administration of antimicrobial agents thereafter. It was supposed that most of MRSA isolates from sputum were not the causative organism of the respiratory tract infection.


[Bacteremia due to methicillin-resistant Staphylococcus aureus (MRSA)].

Bacteremia due to methicillin-resistant Staphylococcus aureus (MRSA) is most likely to occur in compromised patients with prolonged hospitalization who are receiving antibiotics, particularly beta-lactam ones. The clinical picture of MRSA bacteremia is almost the same as that of bacteremia due to methicillin-sensitive S. aureus. There seems to be no significant difference in prognosis between the two types of staphylococcal bacteremia when patients in the same disease category are considered. Vancomycin is at present the only antibiotic for the treatment of MRSA bacteremia. It is therefore important to use the drug adequately so as to prevent its adverse effects and delay the appearance of resistant organisms.


[Clinical spectrum of antibiotic associated enterocolitis due to methicillin resistant Staphylococcus aureus].

Historically, various types of antibiotic-associated diarrhea have been recognized. In the 1950-1960s, multi-resistant Staphylococcus aureus was implicated to be major cause of antibiotic-associated diarrhea, especially pseudomembranous enterocolitis. In the late 1970s, a new type of antibiotic-associated diarrhea, which is characterized by pseudomembranous colitis and lack of fecal multi-resistant S. aureus, usually following lincosamide administration, was recognized. Many studies have revealed the pathogenic roles of Clostridium difficile in these patients. Recent emergence of methicillin resistant S. aureus (MRSA) provokes another type of antibiotic-associated diarrhea. We have tried to isolate S. aureus and C. difficile from 150 faecal samples of patients with antibiotic-associated diarrhea. S. aureus alone was isolated from 32 (21.3%) samples. C. difficile alone was isolated from 51 (34.0%) samples, and, both were detected in 23 (15.3%) samples. 90.9% of S. aureus were MRSA. Comparing the clinical features of these cases, patients with both C. difficile and MRSA showed more serious clinical features. The patients who had undergone laparotomy were accompanied by shock and meteorism, more often than patients without laparotomy. The management of antibiotic-associated diarrhea due to MRSA is discussed.


[Postoperative MRSA infections in digestive tract surgery].

MRSA strains were first isolated in 1981 and have increased markedly from 1985 in our surgical ward. One hundred and ninety four strains of MRSA were isolated and 81 cases developed critical infections which were associated with enterocolitis, pneumonia and sepsis. There were many cases in esophageal cancer patients. Bacteriological features of the MRSA strains clearly changed in 1985 from IV to II coagulase type, accompanied with high resistance for antibiotics. Our management against nosocomial infection for MRSA started from April 1988. The number of MRSA cases decreased in 1989, increased in 1990 and decreased again in 1991. We are confident that our management is effective and we will take further efforts to choose the most adequate antibiotics after surgery in our surgical ward.


[MRSA infections in multiple trauma patients].

Multiple trauma patients requiring prolonged intensive care are at high risk of MRSA infections. Surgical debridement and proper antibiotic prophylaxis combined with isolation of this compromised host from indigenous bacteria are the mainstays of initial therapy to prevent this complication. If this develops postoperatively, the sites of infection vary among the patients, such as urinary tract, surgical wounds, the abdomen, respiratory tract, vascular catheters, etc. Clinical evidence of sepsis suggests that intra-abdominal and respiratory tract infection are major contributors to mortality. In a postoperative multiple trauma patient, with pneumonia, thoracic empyema, intraabdominal abscess, wound infection and sepsis caused by MRSA, surgical drainage of the abscess with systemic infusion of vancomycin was effective and resulted in full recovery.


[MRSA infection and toxic shock syndrome in burn patients].

In burn patients, MRSA was detected in the wound from the early stage to the wound closure stage. It is after the middle stage that sepsis by MRSA occurs. In comparison with Gram-negative bacilli, MRSA caused fewer sudden deaths, except for complications of toxic shock syndrome (TSS); MRSA was not considered to have a significant effect. The presence of a path of invasion into the blood other than the wound was suspected. Investigation of 35 Staphylococcus aureus sepsis patients (25 infected with MRSA) revealed that diagnosis is difficult when severe TSS occurs as a complication in sepsis. No correlation was found between toxic shock syndrome toxin-1 production by the bacterium detected and the onset of TSS. These findings suggest strong dependency upon the action of another toxin or endotoxin produced by Staphylococcus aureus and upon the immune condition of the host.


[MRSA sepsis of premature infants].

During the 12 year period from 1978 to 1990, 112 mature newborn and premature infants were diagnosed as sepsis in our nursery. The first case of MRSA sepsis was found in 1985. Since then, cases abruptly increased in number and 31 cases were found in total. Seven cases died and 24 were cured. Antibiotics such as AMK, MINO, IPM were effective. As the sensitivity of these drugs has been gradually dropping, we believe that VCM will be selected as the first choice. Early diagnosis and therapy are most important. Daily measurement of low level CRP (0.1 to 1.0 mg/dl) is useful and careful management is necessary in the course of significant PDA.


[MRSA infections in the neonatal unit].

MRSA infection in the neonatal unit is discussed, presenting our experience of an epidemic of TSST-1-positive strains in the Teikyo University Hospital in 1988-1989. Neonatal MRSA infections were experienced for the first time in 1982, and a few cases were treated each year from 1984 to 1987. In October 1988, MRSA-colonized and/or diseased cases increased abruptly after admission of several MRSA-positive neonates. The new strains were TSST-1-positive, coagulase type II organisms, which were multiply resistant, including gentamicin. The disease/colonization ratio was 37.0% in 108 colonized neonates. Among them, 5 cases of atypical TSS were experienced. The main clinical manifestation was an abrupt onset of shock with leukopenia. Some of the cases were afebrile and rash was hard to recognise. For the successful treatment of neonatal TSS, not only effective antibiotics but also prompt exchange transfusions were needed.


[MRSA ocular infections].

Staphylococcus aureus and Staphylococcus epidermidis are organisms that frequently cause conjunctivitis, keratitis and endophthalmitis. MRSA comprised about 25% of the S. aureus isolated from ocular infections; most were from compromised host. MRSA was resistant to penicillins, cephems and macrolides but was sensitive to amikacin, netilmicin, minocycline and ofloxacin. Ofloxacin-resistant strains, however increased rapidly. Topical vancomycin, arbekacin and minocycline were used when commercially available antibiotics were inadequate.


[MRSA infections in otorhinolaryngology].

Infections caused by MRSA in otorhinolaryngology were evaluated in this study. From October 1990 to the end of September 1991, MRSA was detected in one hospitalized patient and 14 outpatients of the otorhinolaryngology department. MRSA was detected in the tonsils of five patients other patients--including four with cancer and other underlying diseases. In two of the four patients with chronic otitis media, otorrhea was stopped by disinfecting external ear toxin. Osteomyelitis of the upper jaw in neonates and infants must be treated in consideration of MRSA, as it is a hospital infection caused by cephem-resistant Staphylococcus.


[Methicillin-resistant Staphylococcus aureus in dermatology].

Staphylococcus aureus (SA) is among the most important causes of skin infections. The incidence of Methicillin-resistant SA (MRSA) strains isolated from skin and skin structure infections was about 20-40%. In deep-seated pyoderma such as furuncle and furunculosis, MRSA was more frequently isolated than in other type of infectious diseases of the skin. But the incidence was gradually increasing. As to coagulase typing, type IV was most frequently isolated in MRSA. The damaged skin is easily colonized by high numbers of SA on its surface and within hair follicles. Through the indwelling catheters or decubitus SA on the skin could cause easily severe systemic MRSA infections such as sepsis or endocarditis of in-patients.


[MRSA infection in urological field].

During the 12-month period ending December 1990, urological infections due to MRSA were found 18 patients (14 hospitalized and 4 outpatients) and clinical features of these cases were reviewed. Ten patients with MRSA in the urine were asymptomatic, but MRSA sepsis due to severe pyelonephritis occurred in one patient and extensive treatment was required. Factors contributing to MRSA infections were mainly indwelling catheterization, preceding antimicrobial therapy (new quinolones and new cephems), and obstructive disease. Strict management of indwelling catheters and drainage of wounds is especially important, because MRSA infections are considered to be nosocomial.


[MRSA infections in obstetrical and gynecological fields].

The rate of isolation of S. aureus from the materials collected from the genital tract in gynecological and obstetrical fields is very low about 11.5%. The chances to encounter infections caused by MRSA are therefore few. The countermeasures for the important infections caused by MRSA, nosocomial infections, become more important hereafter. Greater attention to MRSA in obstetrical field, especially, in the perinatal period, such as mastitis in puerperium and infections in high risk infants is necessary.


[Methicillin-resistant Staphylococcus aureus infection in the orthopaedic field].

A retrospective report regarding MRSA infections, related to wards and physicians in the hospital, was carried out. The number of the patients infected by MRSA in every wards was compared. Less patients with MRSA infection ware observed in the orthopaedic ward. An epidemiologic study using culture sampling of MRSA was performed at the isolated room for the patient with MRSA infection. Positive cultures were also detected in several areas in the ward, in addition to that room. Then the infection risk of every places in the hospital was suspected. Four cases of orthopaedic patients with MRSA were described.


[Methicillin resistant Staphylococcus aureus (MRSA) infection in geriatric hospital--management for infected decubital ulcer].

Wide spread of MRSA infection in geriatric hospitals indicated two important problems which must be resolved. One is how we can eradicate MRSA in the elderly, and the other is how we can control cross infections of MRSA within the hospital. The presence of infected decubital ulcers in the elderly make it difficult to answer these problems. Usually, MRSA and Pseudomonas aeruginosa which is isolated from decubital ulcers act as colonizers on the surface of granulated wounds but do not contribute to clinical symptoms. However, these colonizers can be the source of cross infection toward other debilitated patients. The actual management for decubital ulcer infected by MRSA are discussed from the above viewpoints.


[Post-antibiotic effect and clinical significance].

The postantibiotic effect (PAE) is the phenomenon of suppression of bacterial growth after brief antimicrobial exposure to microorganisms. The presence of PAE may be an important consideration in designing antibiotic dosage regimens. Antimicrobials with minimal or lesser PAEs may require serum concentration above MIC or entire dosing interval. Several antimicrobial actions are affected on the PAE phase, eg. "postantibiotic sub-MIC effect". Moreover, the PAE may contribute to the efficacy on host-parasite relationship. This phenomenon is discussed.


[Considerations on MRSA infections in relation to modern chemotherapy].

Before the antibiotic era of medicine began about 50 years ago, the prognosis for patients with severe staphylococcal infections was extremely poor. In the early 1940s, the introduction of penicillin G (PCG) temporarily solved the problem of staphylococcal infections, but the continued use of this agent caused the selection of resistant strains, which produced penicillinase. Accordingly, the value of PCG had seriously reduced by 1948. By then S. aureus had acquired multiple resistance to virtually all available systemic antibiotics, including aminoglycosides, tetracycline, chloramphenicol and the macrolides. The introduction of the semisynthetic penicillinase resistant penicillins (e.g., methicillin, oxacillin) and the 1st generation cephems brought about a general decline in the prevalence of multiply resistant S. aureus during the early 1960s. The strains of methicillin-resistant S. aureus (MRSA) were initially detected in 1961 in the United Kingdom, shortly after methicillin came into clinical use, and they have subsequently been isolated in many other parts of the world including Japan. In Japan, most strains of MRSA now represent high level resistance to all antibiotics, except for a few antibiotics, such as vancomycin and arbekacin, and therefore, they posed a serious problem clinically and epidemiologically, via immuno-suppressed inpatients, in particular, as the causative pathogen of nosocomial infection. The appearance and spread of such MRSA strains in Japan may be due to the extensive use of broad spectrum antibiotics, particularly the 3th generation cephems. It is now important to reconsider the modern chemotherapy which evoke serious drug-resistant mutants, such as MRSA.


[Basic aspects of Staphylococcus aureus and MRSA--typing and extracellular toxins and proteins].

Many kinds of staphylococcal typing systems have been developed and tested for epidemiology of Staphylococcus aureus. Coagulase typing and phage typing are more useful and important for this epidemiology. The methods of coagulase typing and phage typing were discussed in this paper. A large number of toxins and proteins of Staphylococcus aureus have been released in the field of infectious environment. Some of these toxins and proteins, working as causative agents of staphylococcal infection, are of interest and discussed here. MRSA shows the same mechanisms of infection as methicillin sensitive Staphylococcus aureus.


[Molecular genetics of MRSA].

Methicillin resistance in staphylococci is explained by any of the several alterations of penicillin-binding proteins. In most (97%) of the cases, however, it is caused by acquisition of mecA gene. The mecA gene seems to be laterally transmissible among various staphylococcal species, although the frequency of transmission may not be high in view of the observed rather homogeneous nature of genetic backgrounds of the MRSA strains which were isolated all over the world. Evolution of MRSA to acquire higher level of resistance to beta-lactam antibiotics has been noticed in recent years. Such phenotypic evolution is explained by a genetic alteration involving the mec regulator genes, mecR1 and mecI, of the prototype MRSA strain.


[A guide to prevent infectious disease due to MRSA].

Now in Japan, infectious diseases due to MRSA is an important problem to solve and it has a growing social interest. It is clearly associated with hospital infections. So most important thing for us is to prevent and treat properly hospital infections. As a result of thorough investigations in a hospital for aged persons and a general hospital, we developed some guidelines to prevent MRSA infections. It is necessary to have a prevention committee in the hospital which will do the followings: Reveal the present condition of hospital infections by thorough investigations, make appropriate choice of antibiotics, good care of patients having infectious diseases due to MRSA, good care of carriers, better use of disinfectants, and education of medical staffs.


[Incidence and antimicrobial susceptibility of clinical isolates of MRSA from 1988 to 1990, from the results of 26 clinical laboratories in Tokyo and the surrounding area].

We made a survey to investigate the incidence of clinical isolation and the trend of antimicrobial susceptibility of Methicillin-resistant Staphylococcus aureus (MRSA), isolated in 26 clinical laboratories. Among the 26 institutions, the frequency of MRSA was 22 to 64% (average: 42.1%) in 1988, 22 to 69% (average: 55.3%) in 1989 and 29 to 76% (average: 56.9%) in 1990, and increasing year by year. MRSA showed poor sensitivity to beta-lactam antibiotics, gentamicin, toburamycin and clindamycin. There was a significant difference in frequency of the minocycline-resistant strains and the ofloxacin-resistant strains among the 26 institutions. Albekacin, netilmicin, and vancomycin were most active against MRSA with a MIC90 of 1, 8 and 1 microgram/ml, respectively.


[Survey of MRSA infection in Ibaraki-ken--Ibaraki Association for infectious diseases].

This study which was undertaken at several major hospitals in Ibaraki-ken revealed that, 1) the proportion of Staphylococcus aureus in all the isolates ranged from 5% to 17% and the prevalence of MRSA in isolates of Staphylococcus aureus varied from 51% to 82% depending upon each individual hospital. 2) the clinical response to FOM and CMZ combination therapy was 88.9% and, to FOM and CZON was 57.1% showing no statistical differences between the two regimens. 3) in vitro analyses assessed by the FIC index of 251 isolates revealed that FOM had an additive or synergistic effect with CMZ in 53.8%, with CZON in 66.9%, with minocycline (MINO) in 43.8%, with cefamandole (CMD) in 61.8%, with cefazolin (CEZ) in 62.9% and with imipenem/cliastatin sodium (IPM/CS) in 68.9% at all isolates. 4) the cumulative curve of susceptibility to single CMZ and the combination of CMZ and FOM revealed that the blood levels of CMZ at 3 hours after intravenous administration covered 57% of isolates when used alone and 82% of isolates when in combination with FOM. The blood levels of CZON at 3 hours covered 5% of isolates when used alone and 41% when in combination with FOM. The extent of the therapeutic effect increased from 6% to 42% by CMD, from 12% to 54% by CEZ, from 20% to 58% by IPM/CS and from 78% to 84% by MINO. The combination of CMZ and FOM was found to be the most effective for enhanced effects on MRSA in vitro.


[Methicillin-resistant Staphylococcus aureus (MRSA) isolated in hospitals in Fukuoka City area].

Bacteriological and clinical studies were carried out on 280 strains of Staphylococcus aureus isolated in hospitals in Fukuoka city area from September 1990 to March 1991. Of all S. aureus strains studied 116 (41.4%) were methicillin-resistant. The proportion of MRSA in S. aureus isolates from outpatients was 10% (11/109), 69.2% (90/130) in those from inpatients. The average age of patients with isolated MRSA was 70.5 +/- 16.9 years and that of patients with isolated MSSA, 44.2 +/- 29.3. MRSA strains were recovered mainly from sputum and pus. The isolation rate did not vary significantly with hospitals of different size (number of beds). Of all MRSA strains 48 (41.3%) produced coagulase type VII. As for drug susceptibility, MRSA strains with coagulase type VII were more sensitive to clindamycin and more resistant to minocyclin compared to MRSA with other coagulase types.


[Isolation and antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) at Kumamoto University Hospital].

An increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) has created a serious therapeutic problem. During the period from July to December 1987, the prevalence of MRSA was only 72 strains (35.8%) of 201 total staphylococcal isolates. Since then, the frequency of MRSA has markedly increased to 67.3% in 1989, and at that time it was estimated that 30 patients (3.5%) of 850 total inpatients became infected with MRSA. In an early study in 1987, the majority of the MRSA came from post-operative patients; however in 1989, nearly 40% of MRSA were from internal medicine, mainly from immunocompromised patients. The major source of MRSA isolates was sputum (40%) throughout the years, but the MRSA from blood cultures was first recovered in 1989. Also, the major coagulase serotype of MRSA was type IV (18 of 30) in the 1987-study, then shifted to type II (24 of 40) in 1989. Among the several antimicrobials evaluated, four agents; erythromycin, minocycline, ofloxacin, and gentamicin revealed increasing MICs when compared with the results obtained for the MRSA isolates in 1987 and 1989. In particular, the most of the MICs to minocycline and ofloxacin were categorized to be highly susceptible (less than or equal to 0.39 micrograms/ml) or resistant (greater than or equal to 25 micrograms/ml). Vancomycin, currently licensed for the MRSA infection, will be highly effective both in vitro and in vivo; however, it examinative of the MRSA isolates in the clinical laboratories, especially to prevent hospital-acquired infections and to follow up the vancomycin susceptibility will be required.


[Typing of methicillin-resistant Staphylococcus aureus by antibiotic resistance phenotypes as an epidemiological marker in nosocomial infections].

A total of 129 clinical isolates of methicillin-resistant Staphylococcus aureus was tested for the susceptibility to 28 antibiotics, antiseptics and heavy metal salts, according to the method of Gillespie et al. The strains showed resistance ranging from 20% to 80%, to 10 agents, such as amikacin, chloramphenicol, clindamycin, gentamicin, neomycin, streptomycin, tobramycin, acriflavine, cadmium nitrate, ethidium bromide. These agents were finally chosen for typing in this study. Strains resistant to 10 agents were distributed into 55 phenotypes. Most strains isolated from one ward belonged to the specified phenotype, whereas strains isolated from other wards were divided into a variety of phenotypes. It seemed to be the occurrence of nosocomial infection in this hospital. This typing method gives the merit to be easy, economical, rapid and reproducible for the epidemiological investigations in the clinical bacteriological laboratory.