acute pyelonephritis complicates 1 - 2% of   all 
 pregnancies , making it one of the most   common medical complications of 
 pregnancy .
escherichia coli remains the most common pathogen 
 isolated in acute antepartum pyelonephritis , and ampicillin has been a mainstay 
 of treatment for antepartum pyelonephritis because of efficacy , cost , and 
 minimal risk to both the mother and fetus . because of its concomitant use in the prevention of 
 neonatal group b streptococcal 
 sepsis , there is concern for increasing trends of ampicillin - resistant 
 organisms . in 1984 , duff reported a 
 22% incidence of ampicillin - resistant e. coli in acute antepartum pyelonephritis . by 2001 , hart reported a 45% incidence of 
 ampicillin - resistant e. coli in acute antepartum pyelonephritis [ 2 , 3 ] .
globally , there are increasing rates of 
 antibiotic - resistant strains of e. coli .
this trend in antibiotic resistance caused 
 the centers for disease control and prevention ( cdc ) to identify investigating 
 the clinical implications of antimicrobial resistance as a priority .
moreover , it has been postulated that 
 infections with antibiotic - resistant organisms may increase the risk of 
 treatment failures and morbidity [ 2 , 5 , 6 ] .
accordingly , we sought to measure the incidence of ampicillin 
 resistance in uropathogens causing acute pyelonephritis in our pregnant patient 
 population and to determine if resistant organisms resulted in different 
 clinical outcomes .
this is a secondary analysis of a prospective longitudinal cohort study of 440 pregnant women diagnosed with acute pyelonephritis .
the original cohort included all pregnant women with antepartum pyelonephritis admitted to parkland memorial hospital , dallas , tx , usa , from january 2000 to december 2001 .
the diagnosis of acute pyelonephritis was made with 
 clinical findings of fever ( temperature  38c ) , flank pain , and 
 costovertebral angle tenderness along with laboratory findings of pyuria or 
 bacteriuria ( 20 bacteria per high power field ) .
clean catch mid - stream urine specimens or 
 catheterized urine specimens were collected for culture .
the presumptive diagnosis of pyelonephritis , 
 however , was made and treatment initiated prior to receipt of culture 
 results . antimicrobial therapy included 
 intravenous ampicillin two grams every six hours and intravenous gentamicin , 
 consisting of a loading dose of 120 mg once followed by 80 mg every eight 
 hours .
antimicrobial sensitivities were performed using a 
 broth microdilution and the study utilized breakpoints established by the clinical and laboratory standards institute ( clsi ) .
antimicrobial sensitivities were not 
 performed on uropathogens with colony counts of less than 100 000 .
ampicillin resistance was defined as a 
 minimum inhibitory concentration ( mic ) greater than 16 g / ml . research nurses routinely entered pregnancy outcomes 
 and complications for all women delivered at parkland hospital 
  into a previously described , validated , and   continuously updated   computerized 
 obstetric database .
antepartum 
 data on women with acute pyelonephritis were entered into a separate research 
 database that included length of hospital stay , days of intravenous antibiotics 
 received , vital signs , respiratory insufficiency , necessity of admission to an 
 extended care unit , amount of iv fluid received , and laboratory evaluations 
 including urine cultures , complete blood count , and creatinine as previously 
 described .
anemia was defined as a 
 hematocrit less than 30% , and renal dysfunction was defined as creatinine 1.2 mg / dl .
respiratory insufficiency was 
 defined as dyspnea , tachypnea , and hypoxemia with radiological signs of 
 pulmonary infiltrates ( information regarding intubation was not recorded ) .
the database created of antepartum pyelonephritis 
 patient outcomes included urine culture results by organism , but it did not 
 originally include information on antibiotic sensitivities .
we subsequently re - examined the medical 
 records of the 440 patients admitted with acute pyelonephritis to review the 
 antibiotic sensitivities of the admission urine cultures and entered these into 
 the database .
these data were 
 subsequently linked electronically to pregnancy outcome data from the obstetric 
 research database .
statistical analyses were performed using sas 9.1 
 ( sas institute , cary , nc , usa ) . 

comparisons were made with the pearson 's chi - square test for categorical data 
 and student 's t - test for continuous data .
for statistically 
 nonnormal data , the wilcoxon rank - sum test was substituted for student 's t - test .
the mantel - haenszel chi - square was used to 
 analyze trends in categorical data .
urine 
 cultures with identification of an organism with sufficient colony forming 
 units for antibiotic sensitivity testing were available for 317 ( 72% ) of the 
 440 initial study patients ( 72% ) .
although additional patients had positive 
 urine cultures , our laboratory did not perform antimicrobial sensitivities for 
 cultures less than 100 000 colony - forming units .
ninety - two percent ( 92% ) of the cultures that had 
 organisms identified and sensitivities performed grew e. coli .
the other organisms identified with 
 sufficient colony - forming units to receive antibiotic sensitivity testing 
 included klebsiella pneumoniae , proteus mirabilis , and enterbacter species .
overall , fifty - one percent ( 51% ) of these organisms were 
 resistant to ampicillin .
we reviewed the demographic characteristics of the 
 patients with ampicillin - resistant and ampicillin - sensitive organisms .
as demonstrated in table 2 , there was no 
 significant difference in the ethnicity of patients with ampicillin - resistant 
 organisms .
the patients with 
 ampicillin - resistant organisms , however , were more likely to be multiparous ( p = .04 ) .
the patients with ampicillin - resistant 
 organisms were also older ( p = .04 ) 
 ( see table 3 ) .
we analyzed the hospital courses of women with acute 
 antepartum pyelonephritis comparing patients infected with ampicillin - resistant 
 and ampicillin - sensitive organisms .
as 
 summarized in table 4 , we found no significant differences in length of 
 hospital stay , days of iv antibiotics required , admission to the extended care 
 unit , or rate of hospital readmission .
we also compared the rates of common complications of 
 acute antepartum pyelonephritis between the ampicillin - resistant and 
 ampicillin - sensitive groups .  
patients 
 with ampicillin - resistant organisms did not have higher maximum 
 temperatures ( see table 5 ) .
additionally , infection 
 with ampicillin - resistant organisms was not associated with increased rates of 
 anemia , renal dysfunction , or respiratory insufficiency .
there was also no significant difference in 
 the incidence of preterm birth between the two groups .
we re - evaluated a large prospective longitudinal 
 study of a cohort of women hospitalized with acute antepartum pyelonephritis to 
 measure the incidence of ampicillin resistance in our patient population and to 
 determine if resistant organisms resulted in different clinical outcomes .
our review of the rate of 
 ampicillin - resistance revealed that the majority of organisms cultured   were resistant to ampicillin . as expected , e. coli was the most 
 common pathogen cultured in acute antenatal pyelonephritis , and 51% of e. 
 coli cultures were 
 ampicillin - resistant .
this finding is 
 similar to hart 's finding in 2001 of a 45% rate of ampicillin - resistance in e. coli causing acute antepartum pyelonephritis .
similarly , gupta found that from 1992 
 to 1996 , the rate of ampicillin resistance in e. coli isolates increased 
 from 26% to 34% in women with cystitis .
all 
 the klebsiella organisms cultured were 
 ampicillin - resistant , while all proteus organisms cultured were 
 ampicillin - sensitive .
ninety - eight percent ( 98% ) of klebsiella isolates were 
 ampicillin - resistant , while only 8% of proteus species were ampicillin - resistant .
the initial report from 
 this study found an 11.6% rate of infection with gram - positive organisms , and 
 the majority of these were identified as group b streptococcus .
our laboratory does not perform antimicrobial 
 sensitivities on group b streptococcus or any other gram - positive uropathogens with 
 less than 100 000 cfu .
our analysis of demographic characteristics of women 
 with ampicillin - resistant organisms revealed no association with ethnicity .
it did , however , demonstrate that infection 
 with ampicillin - resistant organisms was more common in older and multiparous patients .
the observed trend of increasing incidence of 
 ampicillin - resistance with increasing age and parity may be due to increased 
 exposures to antibiotics and to prior hospitalizations for deliveries .
either of these events could increase their 
 risk of acquiring resistant organisms compared with patients who are younger 
 and nulliparous .
while the impact of 
 infection with organisms resistant to the initial antibiotic used to treat 
 infection has been studied in septic and icu patients , no similar outcome 
 studies have been conducted in acute antepartum pyelonephritis . in septic patients , infection with -lactam 
 resistant strains of e. coli and klebsiella resulted in 
 significantly higher mortality rates .
other studies comparing patient 
 outcomes between antibiotic - sensitive and antibiotic - resistant infections have 
 shown increased length of hospital stay , increased rates of infectious 
 complications , and increased cost of treatment [ 9 , 10 ] . in light of these 
 studies
, we undertook this analysis to assess if infection with 
 antibiotic - resistant organisms in acute antepartum pyelonephritis would affect 
 patient outcomes . in acute antepartum 
 pyelonephritis , infection with organisms resistant to ampicillin did not affect 
 patient outcomes in terms of the course of their hospital stay or the frequency 
 of common complications of pyelonephritis . 
 the similarities in outcomes between patients infected with 
 ampicillin - resistant and ampicillin - sensitive organisms are reassuring in light 
 of the common use of ampicillin and gentamicin to treat acute antepartum 
 pyelonephritis and the increasing reports of ampicillin - resistant organisms . 

the first explanation is 
 that while over fifty percent of the organisms cultured were resistant to 
 ampicillin , all patients were   receiving gentamicin in addition to 
 ampicillin .
moreover , only a single 
 patient had an organism that was resistant to gentamicin .
ampicillin and gentamicin may create a 
 pharmacologic synergy that may also explain the discrepancy between in vitro susceptibilities and in 
 vivo findings .
this also raises the question of whether treatment 
 with gentamicin alone would be adequate to treat the majority of cases of acute 
 antepartum pyelonephritis .
the second explanation is 
 that while these organisms were microbiologically resistant to ampicillin , they 
 may not have been clinically resistant to ampicillin .
. it can be 
 defined genetically ( genotypically ) , meaning that there is a genetic mechanism in 
 the bacteria that encodes for resistance against a class of antibiotics .
alternatively , resistance can be defined , as 
 it was here , microbiologically ( phenotypically ) meaning that there is an 
 abnormally elevated minimum inhibitory concentration ( mic ) observed in 
 laboratory testing .
finally , resistance 
 can be defined clinically as the failure to demonstrate improvement in the 
 patient receiving the medication .
wing et al . alluded to this 
 difference in microbiological resistance versus clinical resistance in their 
 assessment of the utility of blood and urine culture results in acute 
 antepartum pyelonephritis . in their study , some patients were receiving 
 ampicillin and gentamicin while others were receiving monotherapy with a 
 first - generation or third - generation cephalosporin .
although they had ampicillin resistance rates 
 of 46% and first - generation cephalosporin resistance rates of 7% , 94% of 
 patients were given appropriate antibiotics when  appropriate antibiotics 
of these , the majority of changes were due to 
 perceived lack of clinical response , including persistent fever beyond 72 hours , rather than due to the sensitivity results of the cultures .
this finding led wing et al . to conclude that 
 blood and urine cultures with sensitivities have limited practical utility in 
 the majority of patients with acute antepartum pyelonephritis . while we believe that culture results continue to have a role in determining the organisms causing infection , the success of therapy in sterilizing the urine , and the antibiotic resistance rates within our hospital , we agree that changes in antimicrobial therapy should be guided by clinical response rather than solely based on culture results .
first , we included only patients managed as inpatients , and our findings may not apply to 
 populations managed as outpatients . 

second , the only patients who had cultures with antibiotic sensitivities 
 were those with gram - negative organisms , so we do not know the rate of 
 ampicillin resistance in other pathogens or whether ampicillin resistance in 
 those organisms would affect outcomes .
in 
 summary , we found no association with adverse clinical outcomes in gravidas 
 with acute pyelonephritis treated with ampicillin and gentamicin that had 
 ampicillin - resistant gram - negative uropathogens .
these data should reassure clinicians that 
 this well - established treatment regimen is still effective in the management of 
 acute antepartum pyelonephritis in most settings .
 
 objective . to measure the incidence of ampicillin - resistant uropathogens in acute antepartum pyelonephritis and to determine if patients with resistant organisms had different clinical outcomes . 
 study design . 
 this was a secondary analysis of a prospective cohort study of pregnant women admitted with pyelonephritis , diagnosed by standard clinical and laboratory criteria . 
 all patients received ampicillin and gentamicin . results . 
 we identified 440 cases of acute pyelonephritis . 
 seventy - two percent ( 316 cases ) had urine cultures with identification of organism and antibiotic sensitivities . 
 fifty - one percent of uropathogens were ampicillin resistant . 
 the patients with ampicillin - resistant organisms were more likely to be older and multiparous . 
 there were no significant differences in hospital course ( length of stay , days of antibiotics , ecu admission , or readmission ) . 
 patients with ampicillin - resistant organisms did not have higher complication rates ( anemia , renal dysfunction , respiratory insufficiency , or preterm birth ) . 
 conclusion . 
 a majority of uropathogens were ampicillin resistant , but no differences in outcomes were observed in these patients . 
1. INTRODUCTION
2. MATERIALS AND METHODS
3. RESULTS
4. DISCUSSION
5. CONCLUSIONS