Single dose azithromycin versus ciprofloxacin for cholera in children: A randomized controlled trial Randomised double blind trial of single dose doxycycline for treating cholera in adults. Single-dose azithromycin for the treatment of cholera in adults. Antimicrobial Treatment of Adults with Cholera Due to Vibrio cholerae 0139 (Synonym Bengal) Controlled Comparison of Tetracycline and Furazolidone in Cholera* Single-dose ciprofloxacin versus 12-dose erythromycin for childhood cholera: a randomised controlled trial Optimal antibiotic therapy in cholera. Tetracycline in the treatment of severe cholera due to Vibrio cholerae O139 Bengal. Comparative effectiveness of co-trimoxazole and tetracycline in the treatment of Cholera. Single dose tetracycline in cholera. Single-dose treatment of cholera with furazolidone or tetracycline in a double-blind randomized trial. Double-blind, randomized, controlled clinical trial of norfloxacin for cholera. Erythromycin and trimethoprim-sulphamethoxazole in the treatment of cholera in children. Norfloxacin versus co-trimoxazole in the treatment of acute bacterial diarrhoea: a placebo controlled study. Single-Dose Doxycycline for Cholera Effects of Doxycycline in Actively Purging Cholera Patients: a Double-Blind Clinical Trial Comparative trial of erythromycin and sulphatrimethoprim in the treatment of tetracycline-resistant Vibrio cholerae O1. Azithromycin in the treatment of cholera in children Randomised controlled comparison of single-dose ciprofloxacin and doxycycline for cholera caused by Vibrio cholerae O1 or O139 Antimicrobial Treatment of Cholera Treatment of acute bacterial diarrhea: a multicenter international trial comparing placebo with fleroxacin given as a single dose or once daily for 3 days. Pivmecillinam, co-trimoxazole and oral mecillinam in gastroenteritis due to Vibrio spp. Comparison of the efficacy of tetracycline and norfloxacin in the treatment of acute severe watery diarrhea. Efficacy of norfloxacin and doxycycline for treatment of vibrio cholerae 0139 infection. Comparison of single-dose azithromycin and 12-dose, 3-day erythromycin for childhood cholera: a randomised, double-blind trial Norfloxacin monodose use in patients with cholera in Salta Argentina. Antibiotic therapy of cholera. Comparative Trial of Tetracycline, Chloramphenicol, and Trimethoprim Sulphamethoxazole in Eradication of Vibrio cholera El Tor Oral Ciprofloxacin in the Treatment of Cholera Efficacy of a single dose of furazolidone for treatment of cholera in children. Single dose ciprofloxacin in cholera. Ciprofloxacin for the treatment of cholera: a randomized, double-blind, controlled clinical trial of a single daily dose in Peruvian adults. Comparative trial of five antimicrobial compounds in the treatment of cholera in adults. Furazolidone in the treatment of cholera. Doxycycline in the treatment of cholera.
Objective To compare the clinical and bacteriological success of single dose treatment with azithromycin and ciprofloxacin in children with cholera . Design R and omized , open labelled , clinical controlled trial . Setting Tertiary care hospital . Participants 180 children between 2–12 years , having watery diarrhea for ≤24 hr and severe dehydration , who tested positive for Vibrio cholerae by hanging drop examination or culture of stool . InterventionAzithromycin 20 mg/kg single dose ( n=91 ) or Ciprofloxacin 20 mg/kg single dose ( n=89 ) . Dehydration was managed according to WHO guidelines .Main outcome measures Clinical success ( resolution of diarrhea within 24 hr ) and bacteriological success ( cessation of excretion of Vibrio cholerae by day 3 ) . Secondary outcome variables included duration of diarrhea , duration of excretion of Vibrio cholerae in stool , fluid requirement , and proportion of children with clinical or bacteriological relapse . Results The rate of clinical success was 94.5 % ( 86/91 ) in children treated with Azithromycin and 70.7 % ( 63/89 ) in those treated with Ciprofloxacin [ RR ( 95 % CI)=1.34 ( 1.16–1.54 ) ; P<0.001 ] . Bacteriological success was documented in 100 % ( 91/91 ) children in Azithromycin group compared to 95.5 % ( 85/89 ) in Ciprofloxacin group [ RR ( 95 % CI)=1.05 ( 1.00–1.10 ) ; P=0.06 ] . Patients treated with Azithromycin had a shorter duration of diarrhea [ mean(SD ) 54.6 ( 18.6 ) vs 71.5 ( 29.6 ) h ; mean difference ( 95 % CI ) 16.9 ( 9.6–24.2 ) ; P<0.001 ] and lesser duration of excretion of Vibrio cholerae [ mean(SD ) 34.6 ( 16.3 ) vs 52.1 ( 29.2 ) h ; mean difference ( 95 % CI ) 17.5 ( 0.2–24.7 ) , P<0.001 ] in children treated with Azithromycin vs Ciprofloxacin . The amount of intravenous fluid requirement was significantly less among subjects who received Azithromycin as compared to those who received Ciprofloxacin [ mean(SD ) 4704.7(2188.4 ) vs 3491.1(1520.5 ) mL ; Mean difference ( 95 % CI ) 1213(645.3–1781.9 ) ; P<0.001 ] . Proportion of children with bacteriological relapse was comparable in two groups [ 6.7 % ( 6/89 ) vs 2.2 % ( 2/91 ) ; RR ( 95 % CI ) 0.95 ( 0.89–1.01 ) ; P=0.16 ] . None of the children in either group had a clinical relapse . ConclusionS ingle dose azithromycin is superior to ciprofloxacin for treating cholera in children OBJECTIVE --To compare the efficacy of a single dose of doxycycline ( 200 or 300 mg ) with the st and ard multiple doses of tetracycline in patients with cholera . DESIGN --R and omised double blind controlled trial . Patients were given a single 200 mg dose of doxycycline , a single 300 mg dose of doxycycline , or multiple doses of tetracycline ( 500 mg , six hourly intervals ) . SETTING --Hospital in Bangladesh treating diarrhoea . PATIENTS --261 Patients aged over 15 admitted to the hospital with severe dehydration due to acute watery diarrhoea associated with Vibrio cholerae . All vibrios isolated from the stools and rectal swabs of patients , including those patients with prolonged excretion of vibrios , were sensitive to tetracycline . The stools of all patients at admission were negative for shigella and salmonella . INTERVENTIONS --All patients received rapid intravenous acetate solution for the first four hours after admission to hospital . They were then entered in the study and r and omised . Oral rehydration was started immediately after the intravenous treatment . If signs of severe dehydration reappeared during oral treatment patients were given rapid intravenous acetate solution until dehydration was fully corrected . MAIN OUTCOME MEASURES --Stool output in first 24 hours and till diarrhoea stopped , total intake of oral rehydration fluid , duration of diarrhoea , and excretion of vibrio after receiving antibiotic treatment . RESULTS --The median stool outputs during the first 24 hours ( 275 ml/kg body weight ) and till diarrhoea stopped ( 296 ml/kg body weight ) were significantly higher in patients receiving 200 mg doxycycline as a single dose than in patients receiving either st and ard tetracycline ( 242 ml/kg body weight and 254 ml/kg body weight ) or 300 mg doxycycline ( 226 ml/kg body weight and 255 ml/kg body weight ) . Similarly , median consumption of oral rehydration solution ( 18.45 l ) was significantly higher in patients receiving 200 mg doxycycline than in patients receiving either 300 mg doxycycline ( 16.10 l ) or st and ard tetracycline ( 14.80 l ) . Almost equal numbers of patients in each group required unscheduled intravenous acetate solution to correct dehydration during antibiotic treatment . Patients treated with doxycycline ( low or high dose ) , however , had more prolonged excretion of bacteria . CONCLUSIONS --A single 300 mg dose of doxycycline is as effective as the st and ard multiple dose tetracycline treatment for cholera in terms of stool output , duration of diarrhoea , vomiting , and requirement for oral rehydration solution BACKGROUND Single-dose azithromycin is effective in the treatment of severe cholera in children , but its effectiveness in adults has not been evaluated . METHODS We conducted a double-blind , r and omized trial comparing the equivalence of azithromycin and ciprofloxacin ( each given in a single 1-g dose of two 500-mg tablets ) among 195 men with severe cholera caused by Vibrio cholerae O1 or O139 . Patients were hospitalized for five days . A stool culture was performed daily . Primary outcome measures were clinical success ( the cessation of watery stools within 48 hours after drug administration ) and bacteriologic success ( the inability to isolate V. cholerae after 48 hours ) . RESULTS Therapy was clinical ly successful in 71 of 97 patients receiving azithromycin ( 73 percent ) and in 26 of 98 patients receiving ciprofloxacin ( 27 percent ) ( P<0.001 ) and bacteriologically successful in 76 of 97 patients receiving azithromycin ( 78 percent ) and in 10 of 98 patients receiving ciprofloxacin ( 10 percent ) ( P<0.001 ) . Patients who were treated with azithromycin had a shorter duration of diarrhea than did patients treated with ciprofloxacin ( median , 30 vs. 78 hours ) ; a lower frequency of vomiting ( 43 percent vs. 67 percent ) ; fewer stools ( median , 36 vs. 52 ) ; and a lower stool volume ( median , 114 vs. 322 ml per kilogram of body weight ) . The median minimal inhibitory concentration of ciprofloxacin for the 177 isolates of V. cholerae O1 was 0.25 mug per milliliter , which was 11 to 83 times as high as that in previous studies at this site . CONCLUSIONS Single-dose azithromycin was effective in the treatment of severe cholera in adults . The lack of efficacy of ciprofloxacin may result from its diminished activity against V. cholerae O1 strains currently circulating in Bangladesh . ( Clinical Trials.gov number , NCT00229944 . ) Serotyping of Vibrio cholerae is based on the somatic ' 0 ' antigen . Cholera is caused by the 01 serotype ev . cholerae 01 ) , and there were pre­ viously a total of 138 serotypes identified . A new serotype of V. cholerae has recently been identified as the pathogen responsible for explosive outbreaks of severe dehydrating diarrhoea in India and Bangladesh . This has been design ated V. cholerae 0139 . [ 1 ] Since it produces an illness that is clinical ly indistinguishable from cholera , it is considered to be another serotype of V. cholerae that can cause cholera.[2 ] The synonym ' Bengal ' has been proposed because the serotype was first isolated along the Bay of Bengal . Replacement of fluid and electrolyte losses is the most important part of tbe management of patients with cholera caused by V. cholerae 01 or V. cholerae 0139 . Treatment of cholera due to V. cholerae 01 with effective antimicrobials has been useful in shortening the duration of diarrhoea and faecal excretion of the pathogen , and in reduc­ ing the volume of watery stools , with subsequent decreased requirement for rehydration fluids . This r and omised clinical trial was conducted at the Diarrhoea Treatment Centre of the A controlled comparison of furazolidone and tetracycline in the treatment of cholera indicates that , in either dosage used , furazolidone reduced total stool volume by 50 % and duration of diarrhoea by 40 % . These results are comparable to those achieved with tetracycline , which was given in presently recommended dosage . Both furazolidone and tetracycline significantly reduced the rate of stool output within 18 to 24 hours of starting antibiotic treatment . Furazolidone was significantly less effective than tetracycline in rapidly and consistently terminating vibrio excretion . One convalescent carrier of  cholera vibrios was identified among control patients ; none was identified among patients treated with either tetracycline or furazolidone .  All Vibrio cholerae strains tested were sensitive to tetracycline and furazolidone , but larger concentrations of the latter were required to achieve inhibition of growth . It is concluded that tetracycline remains the antibiotic of choice in cholera but that furazolidone would be a useful adjunct to cholera therapy when tetracycline is unobtainable or if strains of V. cholerae with clinical ly significant resistance to tetracycline should be encountered BACKGROUND Single-dose ciprofloxacin is effective for the treatment of severe cholera in adults . We assessed whether single-dose ciprofloxacin would be as effective as 3-day , 12-dose erythromycin in achieving clinical cure in children with severe cholera . METHODS We did a r and omised , open label , controlled trial in children age 2 - 15 years with V cholerae O1 or O139 present in stool on dark-field microscopy . Children received either a single 20 mg/kg dose of ciprofloxacin ( n=90 ) or 12.5 mg/kg of erythromycin ( n=90 ) every 6 h for 3 days , and remained in hospital for 5 days . The primary outcome was clinical success of treatment , defined as cessation of watery stools within 48 h of start of drug treatment . Analysis was per protocol . This study is registered with the Clinical Trials.gov Protocol Registration System at http://www . clinical trials.gov ( registration number NCT 00142272 ) [ corrected ] FINDINGS Of 180 children r and omised 162 completed the study .  Treatment was clinical ly successful in 60 % ( 47/78 ) of children treated with ciprofloxacin and in 55 % ( 46/84 ) of those treated with erythromycin ( difference 5 % [ 95 % CI -10 to 21 ] ) . Children receiving ciprofloxacin  vomited less often ( 58%vs 74 % ; difference 16 % [ 2 to 30 ] ) , had fewer stools ( 15 vs 21 ; 6 [ 0 to 9 ] ) , and less stool volume ( 152 vs 196 mL/kg ; 43 mL/kg [ 13 to 87 ] ) than those receiving erythromycin .  Bacteriological failure was more common in ciprofloxacin-treated patients ( 58%vs 30 % ; 28 % [ 13 to 43 ] ) than erythromycin-treated patients . INTERPRETATION Single-dose ciprofloxacin achieves clinical outcomes similar to , or better than , those achieved with 12-dose erythromycin treatment in childhood cholera , but is less effective in eradicating V cholerae from stool Intravenous replacement of the diarrhoeal fluid and electrolyte losses to restore a physiological state of hydration is well established as the basis for successful management of cholera patients . The use of oral tetracycline as an adjunct in reducing the volume and duration of diarrhoea , as well as eradicating the vibrio from the gastrointestinal tract , has been proven beneficial . An optimal dose schedule has not been established previously , and clinical or bacteriological relapses have been generally reported . Chloramphenicol and sulfaguanidine have also been mentioned as adjuncts . The present report shows that 3 g or 4 g of tetracycline in one of 3 dose schedules were predictably efficacious .  Chloramphenicol , while of benefit , was not as effective and sulfaguanidine was of little benefit compared with the tetracycline regimens Vibrio cholerae O139 synonym Bengal , recognized in 1993 , is the second member in the list of about 200 serogroups of V. cholerae with epidemic and p and emic potential . Although replacement of fluids and electrolytes remains the cornerstone in the management of cholera , antimicrobial therapy can significantly shorten the duration of diarrhoea , and reduce stool volume and requirements ofrehydration fluids . The role of antimicrobial therapy on the natural course of the disease caused by this relatively new pathogen has not been systematic ally assessed . A r and omized , double-blind , placebo-controlled clinical trial was conducted to evaluate the efficacy of  tetracycline in the treatment of adults with severe cholera due to V. cholerae O139 Bengal . Forty-three adult males with severe cholera were r and omly allocated to receive either 500 mg of tetracycline ( n=21 ) or placebo ( n=22 ) for three consecutive days . Demographic and clinical characteristics of these patients on admission were comparable . Tetracycline therapy was associated with significantly reduced total median ( inter-quartile range ) stool volume [ 216.48 ( 90.18 - 325.22 ) mL/kg vs 334.25 ( 215.12 - 537.64 ) mL/kg ; p=0.001 ] , higher rates of clinical cure ( 81 % vs 27 % ; p<0.001 ) , and shorter median ( inter-quartile range ) duration of diarrhoea [ 32 ( 24 - 48 ) hours vs 80 ( 48 - 104 ) hours ; p<0.001 ] . The mean + /- ( SD ) requirement of intravenous fluid was not significantly different between the two groups [ 146.42 + /- 42.12 mL/kg vs 150.44 + /- 27.21 mL/kg ; p=0.70 ] . The median ( inter-quartile range ) duration of faecal excretion of V. cholerae O139 was significantly shorter in the tetracycline group than the placebo group [ 1(1 - 2 ) day vs 5 ( 3 - 6 ) days ; p<0.001 ] . The results of the study indicate that tetracycline therapy is clinical ly useful in the treatment of severe cholera due to V. cholerae O139 Bengal The purpose of the study reported here was to compare the bactericidal effectiveness of tetracycline and co-trimoxazole ( a combination of sulfamethoxazole and trimethoprim ) in treating cholera . The study , an open-ended r and om trial using adult patients with cholera cases confirmed by stool culture , was carried out in March 1993 at the Cholera Treatment Unit ( CTU ) of the Hospital de Apoyo Departmental María Auxiliadora in Lima , Peru . A total of 107 subjects were divided into two groups ( A and B ) . The 50 in Group A received 500 mg of tetracycline orally every 6 hours for 3 days ; the 57 in Group B received co-trimoxazole ( 160 mg of trimethoprim and 800 mg of sulfamethoxazole ) orally every 12 hours for 3 days . The two groups were comparable in terms of age , sex , duration of symptoms prior to hospital admission , time at which antibiotic treatment was initiated , and clinical evolution . Control stool cultures of specimens obtained after treatment showed Vibrio cholerae O-1 present in 2 % of the Group A and 12.3 % of the Group B patients , and also showed V. cholerae non-O-1 present in 2 % of the Group A patients and 3.5 % of the Group B patients . Overall , it was concluded that both therapeutic treatment regimens were effective and that the strains of V. cholerae observed in the southern sector of the city of Lima were still susceptible to both antibiotics A r and omised clinical trial was carried out to explore the efficacy of single dose tetracycline therapy in cholera . One hundred and eighteen adult patients were assigned to receive either tetracycline in a single 1 g , or a single 2 g dose , or tetracycline 500 mg every six hours four times , or no antibiotics as controls . The means of total liquid stool volumes after treatment were lower in the single 1 g dose group ( 168.0 + /- 20.9 ml/kg ) , in single 2 g dose group ( 229.5 + /- 45.6 ml/kg ) , and multiple dose group ( 214 + /- 28.5 ml/kg ) , than in the control group ( 499.1 + /- 56.5 ml/kg ) ( p less than 0.05 ) . Similarly , the means of duration s of diarrhoea and intravenous fluid requirements were significantly lower in the single dose and multiple dose tetracycline groups , than in the controls ( p less than 0.05 ) . The mean duration s of excretion of Vibrio cholerae were significantly shortened from 3.9 + /- 0.2 days in the control group to 1.9 + /- 0.2 days in single 1 g dose , to 2.2 + /- 0.4 days in single 2 g dose and 1.3 + /- 0.1 days in multiple dose groups , respectively ( p less than 0.05 ) . Three patients in the single 1 g dose group and two patients in single 2 g dose group had clinical relapses with excretion of V cholerae during the relapses , but this was not significantly more frequent than that in the multiple dose group ( p greater than 0.05 ) . These findings suggest that although multiple dose tetracycline therapy remains the best choice , a single dose of either 1 g or 2 g tetracycline appears to be a reasonable alternative for the treatment of cholera as an adjunct to rehydration therapy To evaluate single doses of 400 mg of furazolidone and 1 g of tetracycline given orally to patients with diarrhea due to Vibrio cholerae , we studied 87 adults in a r and omized , double-blind , placebo-controlled trial . All patients received intravenous fluids for rehydration and no other drugs . The total volumes of stool ( mean + /- st and ard deviation ) during a 6-day period after treatment were significantly smaller in the tetracycline group ( 10.5 + /- 8.6 liters ) than in the furazolidone group ( 20.9 + /- 15.9 liters ) and the placebo group ( 19.1 + /- 10.5 liters ) ( P less than 0.01 ) . The duration of diarrhea and volumes of intravenous fluids were also significantly reduced in the tetracycline group ( P less than 0.05 ) . However , there were no differences between the furazolidone and the placebo groups with regard to stool volume , intravenous fluid , and duration of diarrhea . Within 48 h of treatment , tetracycline significantly reduced the number of patients with positive stool cultures for V. cholerae ( 37 % ) compared with furazolidone treatment ( 96 % ) and the placebo ( 97 % ) ( P less than 0.001 ) . Although the tetracycline group had a significantly higher incidence ( 61 % ) of bacteriologic relapse ( negative stool cultures on days 2 and 3 , followed by positive cultures afterward ) compared with that in the furazolidone group ( 40 % ) and the placebo group ( 33 % ) , this was not associated with clinical relapse . There were no differences between the furazolidone and placebo groups with regard to any of the bacteriologic responses examined . These data indicate that a single dose of 1 g of tetracycline is effective in the treatment of cholera , but it is asymptomatic bacteriologic relapse . A single dose of 400 mg of furazolidone is not therapeutically effective in cholera In a double-blind , r and omized clinical trial with 78 adults with acute watery diarrhea and severe dehydration , 37 subjects were positive for Vibrio cholerae . In conjunction with rehydration therapy , 13 patients received norfloxacin , 12 received trimethoprim-sulfamethoxazole ( TMP-SMX ) , and 12 received a placebo . Norfloxacin was superior to TMP-SMX and to the placebo in reducing stool output , duration of diarrhea , fluid requirements , and vibrio excretion .  TMP-SMX was no better than the placebo To evaluate the efficacy of erythromycin and trimethoprim-sulphamethoxazole ( TMP-SMX ) in the treatment of cholera in children aged 1 - 8 years , a r and omised clinical trial was conducted at a diarrhoea treatment centre in Bangladesh from December 1991 to June 1992 . Fifteen children received erythromycin , 50 mg/kg per day , in four equally divided doses , 18 children received 10 mg/kg per day of trimethoprim and 50 mg/kg per day of sulphamethoxazole in two equally divided doses ( 12 hourly ) for five days , and 15 children received no antibiotic ; children in all three groups received intravenous cholera saline for severe dehydration and for mild to moderate dehydration , a rice-based oral rehydration solution . The mean stool volumes in mL/kg body weight in the two treatment groups were less than that of the control group , and there were no significant differences in stool volume among the two treatment groups . However , 67 % of the children in the erythromycin group and 82 % in the TMP-SMX group recovered within 72 hours compared to 33 % in the control group ( p < 0.01 ) . Similarly , the bacteriological cures were 80 % in the erythromycin group and 83 % in the TMP-SMX group compared to only 27 % in the control group ( p < 0.001 ) . These results confirm that both erythromycin and trimethoprim-sulphamethoxazole are effective antimicrobials in the treatment of cholera . These drugs are of value specially in younger children in whom tetracycline is contraindicated or when the infecting Vibrio cholerae are resistant to tetracycline The bacteriological and clinical efficacy of norfloxacin 400 mg b.i.d . was compared to those of co-trimoxazole ( 160 mg of trimethoprim plus 800 mg of sulphamethoxazole ) b.i.d . and placebo b.i.d . for the treatment of acute bacterial diarrhoea in a r and omized double-blind trial . Of a total of 450 patients with acute diarrhoea , 303 had positive bacterial cultures and were evaluable for efficacy . The time to elimination of pathogens was significantly ( p less than 0.001 ) shorter in the norfloxacin group than in the co-trimoxazole and placebo groups . At completion of treatment , bacteriological cure was found in 97.9 % , 72.4 % and 38.2 % of patients treated with norfloxacin , co-trimoxazole and placebo , respectively . All pathogens were susceptible to norfloxacin and none of them developed resistance to norfloxacin during treatment . In the co-trimoxazole group , resistance to that antibiotic increased from 2 % at inclusion to 65.6 % at the end of treatment ( p less than 0.001 ) . In patients with shigellosis or cholera , the mean time to normalization of bowel movements was significantly shorter in the norfloxacin and co-trimoxazole groups than in the placebo group ( p less than 0.05 and p less than 0.01 , respectively ) . There were no significant differences between groups with respect to adverse events reported . In conclusion , norfloxacin was well tolerated and highly effective in the treatment of acute bacterial diarrhoea To determine the efficacy of single-dose doxycycline in the treatment of cholera , we carried out a r and omized prospect i ve trial in 65 patients . Treatment consisted of either a single dose of 200 mg of doxycycline ( or 4 mg/kg in patients less than 15 years old ) or multiple doses of doxycycline , 500 mg over 4 days ( or 10 mg/kg in patients less than 15 years old ) . There were no differences between the groups in the volumes of intravenous fluid required , volumes of diarrheal stool , or duration s of diarrhea . The mean duration of positive stool cultures for Vibrio cholerae was similar for the two groups , although in both groups several patients continued to excrete Vibrios in the stool for more than 3 days . Blood levels of antibiotic demonstrated that the doxycycline was absorbed in spite of the rapid transit time associated with severe diarrhea . These results suggest that although tetracycline remains the drug of choice for cholera , doxycycline is a reasonable alternative , and that a single dose of 200 mg ( 4 mg/kg in children ) is effective clinical ly In 51 actively purging cholera patients the efficacy of doxycycline , a long-acting tetracycline , was compared with a placebo and tetracycline hydrochloride .  Seventeen patients who were given doxycycline at the recommended dose of 2 mg/kg at the beginning of the study , at 12 h , and at the repeated dose once daily purged a mean volume of 5.1 liters of stool and received an average of 5.7 liters of intravenous fluid . Nineteen patients receiving the placebo  purged 10.1 liters of stool and received 9.7 liters of fluid . Fifteen patients given tetracycline hydrochloride at 6-h intervals passed 4.8 liters of stool and received 5.5 liters of fluid . The duration s of diarrhea calculated in 8-h periods were 3.5 , 8.0 , and 4.1 h in the respective groups receiving doxycycline , placebo , and tetracycline . The differences between the doxycycline and placebo treatments and the tetracycline and placebo treatments were statistically significant . Those receiving doxycycline became vibrio-free in about 3 days as compared with 2 days for those receiving tetracycline ; the group given the placebo were vibrio positive for the duration of their hospitalization . The results show that in the treatment of cholera the administration of doxycycline once daily has effects equal to those when tetracycline is administered at 6-h intervals . This is a distinct advantage because it decreases the dem and on nursing personnel in epidemics . Also , doxycycline may be safely administered in cases of suspected renal failure from prolonged shock in cholera The efficacy of the 2 antimicrobial compounds , erythromycin and trimethoprim-sulphamethoxazole , were compared in the treatment of the clinical symptoms of cholera and the eradication of Vibrio cholerae O1 organisms from the stools of patients infected with tetracycline-resistant strains . 47 patients with a clinical diagnosis of cholera , without prior antibiotic therapy , were included in the trial and received either erythromycin , trimethoprim-sulphamethoxazole , or a placebo twice daily . The mean number of vibrios per gram of stool decreased from 5.2 x 10(8 ) + /- 0.3 per ml to 0 within 36 h of admission following either erythromycin or trimethoprim-sulphamethoxazole therapy , while organisms persisted in placebo-treated controls for more than 7 d. Clinical ly there was a significant reduction in the number of diarrhoeal stools per day and duration of diarrhoea in the erythromycin-treated group compared with the placebo-treated controls . During the study an isolate resistant to trimethoprim-sulphamethoxazole but sensitive to erythromycin was obtained . As an adjunct to oral rehydration therapy , erythromycin may serve as an effective alternative treatment for cholera , especially in areas where trimethoprim-sulphamethoxazole resistance may be emerging Aim : To evaluate the efficacy of azithromycin in the treatment of cholera in children . Methods : A double‐blind , r and omized , controlled clinical trial on 80 children with acute watery diarrhoea and moderate to severe dehydration compared the efficacy of azithromycin and erythromycin in treating cholera . Data were analysed for 56 patients who were stool culture positive for Vibrio cholerae . In conjunction with rehydration therapy , 29 patients received azithromycin and 27 patients received erythromycin . Patients in the two treatment groups had comparable clinical and blood biochemical characteristics on admission . Results : Patients who received azithromycin had significantly less stool output , shorter duration of diarrhoea and lower fluid intake compared with patients who received erythromycin BACKGROUND Effective antimicrobial therapy can reduce the duration and volume of  cholera diarrhoea by half . However , such treatment is currently limited by Vibrio cholerae resistance to the drugs commonly prescribed for cholera , and by the difficulties involved in the administration of multi-drug doses under field conditions . Because of its favourable pharmacokinetics we thought it likely that single-dose ciprofloxacin would be effective in the treatment of cholera . METHODS In this double-blind study treatment was either a single 1 g oral dose of ciprofloxacin plus doxycycline placebo , or a single 300 mg oral dose of doxycycline plus ciprofloxacine placebo .  130 moderately or severely dehydrated men infected with V cholerae 01 and 130 infected with V cholerae 0139 were r and omly assigned treatment . Patients stayed in hospital for 5 days . We measured fluid intake and stool volume every 6 h , and a sample of stool for culture was obtained daily . The primary outcome measures were clinical success -- the cessation of watery stool within 48 h ; and bacteriological success -- absence of V cholerae from cultures of stool after study day 2 . FINDINGS Among patients infected with V cholerae 01 , treatment was clinical ly successful in 62 ( 94 % ) of 66 patients who received ciprofloxacin and in 47 ( 73 % ) of 64 who receive doxycycline ( difference 21 % [ 95 % Cl 8 - 33 ] ) ; the corresponding proportions with bacteriological success were 63 ( 95 % ) and 44 ( 69 % ) ( 27 % [ 14 - 39 ] ) . Among patients infected with V cholerae 0139 , treatment was clinical ly successful in 54 ( 92 % ) of 59 patients who received ciprofloxacin and in 65 ( 92 % ) of 71 who received doxycycline ( < 1 % [ -9 to 9 ] ) , and bacteriologically successful in 58 ( 98 % ) and 56 ( 79 % ) , respectively ( 19 % [ 9 - 30 ] ) . Total volume of watery stool did not differ significantly between ciprofloxacin-group and doxycycline-group  patients infected with either V cholerae 01 or 0139 . All but one of the V cholerae 01 and all of the 0139 isolates were susceptible in vitro to doxycycline , whereas 48 ( 37 % ) of the V cholerae 01 isolates and none of the 0139 isolates were resistant to tetracycline . Treatment clinical ly failed in 14 ( 52 % ) of 27 doxycycline-treated patients infected with a tetracycline-resistant V cholerae 01 strain , compared with three ( 8 % ) of 37 patients infected with a tetracycline-susceptible strain ( 44 % [ 23 - 65 ] ) . INTERPRETATION Single-dose ciprofloxacin is effective in the treatment of cholera caused by V cholerae 01 or 0139 and is better than single-dose doxycycline in the eradication of V cholerae from stool . Single-dose ciprofloxacin may also be the preferred treatment in areas where tetracycline-resistant V cholerae are common . In V cholerae , in-vitro doxycycline susceptibilities are not a useful indicator of the in-vivo efficacy of the drug Management of dehydration is the most important component in the treatment of severe cholera . However , effective antimicrobial therapy can significantly shorten the duration of diarrhoea and faecal excretion of Vibrio cholerae , and reduce stool volume and requirement for rehydration fluids.[l ] Tetracycline has been used effectively in the treatment of cholera for many years , but resistant strains of V. cholerae 01 have emerged in a number of countries . In Bangladesh , > 90 % of the V. cholerae 01 isolates are currently resistant to tetracycline , furazolidone and cotrimoxazole ( trimethoprim-sulfamethoxazole ) . This r and omised clinical trial was conducted at the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research , Bangladesh to compare the efficacy of  ciprofloxacin , tetracycline , erythromycin , nalidixic acid and pivmecillinam  in the treatment of adults with sever ~ cholera caused by predominantly multiply-resistant strains of V. cholerae 01 This study was design ed to test the efficacy of 400 mg fleroxacin given orally as a single dose or once daily for 3 days against  acute bacterial diarrhea .  A group of 508 adults with acute diarrhea were entered into a r and omized , double-blind , placebo-controlled , multicenter trial . Patients were examined and asked about numbers of liquid stools daily for 3 days and at 5 days after start of treatment . Repeat stool sample s were obtained for culture on days 3 and 5 after start of treatment . A total of 332 patients showed stool cultures positive for bacterial pathogens sensitive to fleroxacin and completed their treatments . Patients treated with fleroxacin , both single-dose and 3-day regimens , showed faster clinical improvement than did placebo-treated patients , as shown by earlier cessation of diarrhea ( p < 0.001 ) and reduction in mean number of loose stools per day on days 2 , 3 , and 5 after start of therapy ( p < 0.05 ) . Bacteriologic efficacy was demonstrated by negative stool cultures for initial pathogens on days 3 and 5 after start of therapy in 94 % of patients treated with single doses of fleroxacin and in 93 % of patients treated with three doses of fleroxacin as compared with 57 % of patients treated with placebo ( p < 0.001 ) . Patients with cholera , shigellosis , and infections due to Vibrio parahaemolyticus showed both clinical and bacteriologic responses to fleroxacin treatment , whereas patients with salmonellosis showed only bacteriologic responses . The good overall clinical and bacteriologic responses of most patients with acute bacterial diarrhea of fleroxacin indicate that this convenient single-dose therapy should be advantageous for empiric treatment of certain diarrheal illnesses The comparative efficacy of antibacterial therapy with pivmecillinam or cotrimoxazole and general supportive care only was studied in patients with severe bacterial gastroenteritis . Overall , treatment with antibiotics proved significantly superior to rehydration alone in 42 children . Active therapy also had a statistically beneficial effect in children infected with Vibrio cholerae and V. parahaemolyticus . Pivmecillinam and co-trimoxazole were equally effective . Pivmecillinam and oral mecillinam appeared to be of equal value in a further 22 adults infected by Vibrio spp . No side-effects were recorded in any of the subjects treated . Further investigations with pivmecillinam and oral mecillinam are advocated Antibiotic treatment appears to shorten the duration of diarrhea and eradicate Vibrio cholerae . The objective of this study was to compare the efficacy of tetracycline with norfloxacin therapy in patients ( adults and children ) with acute severe watery diarrhea caused by VC 01 and VC 0139 . Patients ( adults and children ) with acute severe watery diarrhea admitted to Bamrasnaradura Infectious Disease Hospital , Thail and were r and omized to receive either tetracycline ( 500 mg qid in adults and 12.5 mg/kg qid in children ) or norfloxacin ( 400 mg bid in adults and 7.5 mg/kg bid in children ) for 3 days each . The duration of diarrhea and the fecal shedding were comparable between two groups . Thirteen cases were treated with tetracycline and twelve cases with norfloxacin . The results showed the mean duration of diarrhea in tetracycline-treated and norfloxacin-treated groups were 1.31 and 1.25 days , respectively . The mean fecal shedding in tetracycline-treated and norfloxacin-treated group were 1.38 and 1.33 days , respectively . However , there were no statistically significant differences between two groups of both comparisons ( p > 0.05 ) . All isolates ( VC 01 and VC 0139 ) in this study were susceptible to both antibiotics . Tetracycline therapy is as good as norfloxacin therapy for quick recovery and time for bacterial eradication in patients with acute severe watery diarrhea caused by Vibrio cholerae . Children aged less than 8 years should not use tetracycline therapy because of its toxic effects An open r and omised controlled clinical trial with 160 adults with acute watery diarrhoea and severe dehydration compared the efficacy of varying regimens of norfloxacin and doxycycline for the treatment of cholera caused by Vibrio cholerae 0139 Bengal . Data were analysed for the 111 patients who were faeces culture positive for V. cholerae 0139 . In addition to rehydration therapy , 28 patients received 300 mg of doxycycline as a single dose on admission , 26 patients received norfloxacin 400 mg bd for three days , 28 patients received a single dose of 800 mg of norfloxacin and 29 patients received no antibiotic ( control group ) . Patients in the three treatment groups and control group had comparable characteristics on admission . All three treatment groups had reduced stool output , duration of diarrhoea and fluid intake compared with the control group . Multidose norfloxacin treatment significantly reduced stool output , duration of diarrhoea and fluid requirement compared with the other regimens BACKGROUND Cholera is a major public-health problem , with children most affected . However , effective single-dose antimicrobial regimens have been identified only for adults . Our aim was to compare the efficacy of azithromycin and erythromycin regimens in the treatment of children . METHODS We did a double-blind , r and omised study of 128 severely dehydrated children ( age 1 - 15 years ) with cholera , treated at one of two treatment centres in Bangladesh in 1999 . Children were assigned single-dose azithromycin ( 20 mg/kg bodyweight , maximum individual dose 1 g ; n=65 ) or 12.5 mg/kg erythromycin ( maximum dose 500 mg ; n=63 ) every 6 h for 3 days . Patients stayed in hospital for 5 days . We measured fluid balance every 6 h , and obtained a rectal swab or stool sample for culture daily . Our primary outcome measures were clinical success of treatment-ie , cessation of watery diarrhoea within 48 h- and bacteriological success-ie , absence of Vibrio cholerae O1 or O139 from cultures of stool or rectal swab sample s after study day 2 . Analysis was per protocol . FINDINGS Two children in both groups withdrew from the study , and we excluded one child in the erythromycin group . Treatment was clinical ly successful in 48 ( 76 % ) patients who received azithromycin and 39 ( 65 % ) who received erythromycin ( difference 11 % , 95 % CI -5 to 27 , p=0.244 ) ; and bacteriologically successful in 45 ( 71 % ) and 49 ( 82 % ) patients , respectively ( 10 % , -5 to 25 , p=0.261 ) . Patients treated with azithromycin had a shorter duration of diarrhoea ( median 24 h vs 42 h ; difference 12 h , 0 - 18 h , p=0.019 ) and fewer episodes of vomiting ( 1 vs 4 ; difference 1 episode , 0 - 3 episodes , p=0.023 ) . INTERPRETATION Single-dose azithromycin is as effective for treatment of cholera in children as st and ard erythromycin therapy , but is associated with less vomiting The use of monodose ( 800 mg ) per os of Norfloxacin was evaluated in 32 patients with cholera at Salvador Mazza 's Hospital , Salta , Argentina . It was considered the celerity in negativization of stool culture ( 100 % of cases : 12 hours post administration ) , it efficiency along time ( 24/24 controlled patients were negative at 10th day ) and MIC of isolated strains ( 100 % of strains were sensitive : range 0.008 to 0.016 micrograms/ml ) . It was included oral administration of sorbitol 70 % in peanut oil in order to study patients at 10th day 's control . This method could be an alternative one in the study of asymptomatic carrier . Norfloxacin monodose shows good performance in early negativization of stool culture and it was also effective along the whole observation period , suggesting it could prevent carriage Recent clinical trials having established the value of tetracycline as an adjunct to fluid and electrolyte replacement in cholera treatment , a controlled trial of antibiotic therapy was conducted in Dacca on 318 adults hospitalized for cholera . The effects of 4 antibiotics orally administered in varying dosage schedules were studied . Cholera therapy with tetracycline or chloramphenicol caused a highly significant reduction in the duration of diarrhoea and of positive culture , in stool volume , and in intravenous fluid requirement as compared with the results in controls who received intravenous fluid therapy only . Streptomycin was also effective , but to a lesser degree ; paromomycin was of little value . The severity of dehydration  on admission was significantly related to subsequent duration of diarrhoea regardless of whether antibiotics were given . Increasing age was associated with more prolonged purging in patients receiving antibiotics . Increasing the dose of tetracycline to 2 to 3 times that usually administered , or prolonging treatment from 2 to 4 days , did not enhance the therapeutic results . The effect of  tetracycline  was apparent within a few hours of administration . Bacteriological relapses were seen after discontinuation of therapy in all treatment groups , but were not due to the development of resistant bacteria A comparison of tetracycline , chloramphenicol , and trimethoprim/sulphamethoxazole showed that all hasten the eradication of Vibrio cholerae from the stools of patients with cholera . A four-day period of tetracycline or trimethoprim/ sulphamethoxazole was adequate for eradicating V. cholerae from the stools of all patients , but three days , as suggested by the W.H.O. Expert Committee , was not . Four days of chloramphenicol therapy was sufficient for most patients , but a minority required up to seven days ' therapy . Purging produced reappearance of V. cholerae in the stools of one-eighth of the patients who had had three successive daily negative stool cultures ; such patients are a potential danger to the population Since January 1991 , cholera has emerged as a health problem in Latin AmericaJll The use of antimicrobial agents with recognised in vitro activity against Vibrio strains is recommended for treating severe forms of the disease . El Tor Vibrio cholerae 01 , the pathogen responsible for this epidemic , has been sensitive to all the antimicrobial agents used . However , because of massive use of antibacterials for chemoprophylaxis in some countries in the region , multiplyresistant strains have been reported.£21 During the last few years , this pattern of resistance has been observed in areas where cholera is endemic , making the choice of proper antibacterial treatment difficult . The fluoroquinolones have several properties that make them good alternatives to other antimicrobials in the treatment of enteric diseases , especially when resistant strains are suspected . They have extremely low minimum inhibitory concentrations ( MICs ) against a wide variety of enteropathogens ( including multiply-resistant strains ) such as Salmonella spp . , Shigella spp . , Escherichia coli , V. cholerae and Campylobacter spp . Fluoroquinolones also possess long half-lives , allowing onceor twice-daily administration , and achieve very high drug concentrations in the stool as a result of enterohepatic circulation of the active drug . Additionally , intestinal secretion has been reported with ciprofloxacinPl Lastly , they have a good safety profile.[4,51 Among this class of antimicrobials , ciprofloxacin may be one of the best alternatives for the treatment of cholera . The excellent clinical experience reported with ciprofloxacin in the treatment of shigellosis[61 and typhoid fever[71 supports its potential utility in , the treatment of cholera . In this paper , we preSent our experience with 3 different dosage regimens of ciprofloxacin in the treatment of moderate to severe cholera in adults during the Peruvian cholera epidemic To test the efficacy and safety of furazolidone given as a single dose for childhood cholera , a r and omized double-blind placebo-controlled trial was carried out among 118 culture-positive dehydrated children with diarrhea . Patients were r and omly assigned to one of four groups to receive medication orally in liquid suspension : furazolidone at 7 mg/kg/day once , furazolidone at 7 mg/kg/day divided into four doses for 3 days , placebo once , or placebo for 3 days . After 12 patients with furazolidone-resistant infections were excluded from the analysis of efficacy , it was determined that both groups treated with furazolidone showed significantly higher rates of bacteriologic success ( stool cultures negative for Vibrio cholerae on days 2 to 4 after start of therapy ) and clinical success ( cessation of diarrhea within 72 h after start of therapy ) than corresponding placebo groups ( P less than 0.001 ) . There were no significant differences between responses to the 3-day and single-dose regimens of furazolidone , but there was a trend toward better clinical responses in patients who received furazolidone for 3 days . No patient treated with furazolidone dropped out because of side effects . These results indicate that furazolidone , given as either a single dose or divided doses for 3 days , is effective treatment for childhood cholera To explore the efficacy of single dose ciprofloxacin therapy in cholera , a r and omized , open , controlled clinical trial was carried out . Seventy-four adult patient with positive Vibrio cholerae 01 isolates were assigned to receive either ciprofloxacin in a single dose of 1 g ( CIP1 ) , or ciprofloxacin 500 mg b.i.d . , for 1 day ( CIP2 ) , or doxycycline 100 mg b.i.d . , for 3 days ( D ) , or , for control , no antibiotics .  Mean liquid stool output volume did not show any statistically significant difference among CIP1 , CIP2 and doxycycline groups The mean duration of diarrhoea in CIP1 group , on the other h and , was significantly lower than that from the D group ( p = 0.004 ) , and the control group ( p < 0.001 ) . Bacteriologic clearance at the fourth day of treatment were 95.2 % for CIP1 , 89.5 % for CIP2 , 90.5 % for D group and 15.4 % for the control group . We conclude that a single 1 g ciprofloxacin dose is equivalent to doxycycline in its bacteriologic success but has advantages in shortening the duration of diarrhoea and simplicity of use as a single dose We conducted a r and omized , double-blind clinical trial to compare ciprofloxacin ( 250 mg once a day for 3 days ) with tetracycline ( 500 mg four times a day for 3 days ) in terms of efficacy and safety in the treatment of moderate-to-severe cholera in Peruvian adults . The baseline characteristics of the groups were similar . A total of 202 patients ( 102 in the tetracycline group and 100 in the ciprofloxacin group ) were included in the efficacy analysis . The clinical and bacteriologic efficacies of the two regimens were similar . The study drugs were well tolerated . We conclude that ciprofloxacin given once a day is as effective as the st and ard tetracycline regimen for the treatment of cholera in adults . The ciprofloxacin regimen may represent an alternative to the st and ard treatment in areas where Vibrio cholerae O1 strains that are resistant to commonly used antimicrobials are prevalent To compare the efficacy of ciprofloxacin , erythromycin , nalidixic acid and pivmecillinam in the treatment of tetracycline-resistant strains of Vibrio cholerae O1 in adults , a r and omized , open , clinical trial was conducted . A tetracycline group was used for comparison . Seventy-five adult men infected with V. cholerae O1 were r and omly assigned to receive either 400 mg pivmecillinam or 500 mg of one of each of the other drugs . Ciprofloxacin was given every 12 h and the others every 6 h for 3 d. The mean total stool volume per kg was 155 mL for the ciprofloxacin group , 212 mL for the erythromycin and pivmecillinam groups , 246 mL for nalidixic acid , and 293 mL for tetracycline . The difference between ciprofloxacin and tetracycline was significant ( P = 0.045 ) . After 72 h , diarrhoea had stopped in 14 patients ( 93 % ) in the ciprofloxacin group and 12 ( 80 % ) in the erythromycin group , compared to 5 ( 42 % ) of those receiving tetracycline ( P = 0.006 and 0.049 , respectively ) . Bacteriological clearance was 100 % at 24 h in patients treated with ciprofloxacin compared to 20 % and 8.3 % ( P < 0.001 for both comparisons ) in the erythromycin and tetracycline groups . Ciprofloxacin in conjunction with appropriate fluid therapy was the most effective treatment for cholera in adults ;  erythromycin was the next best Abstract Furazolidone and tetracycline ( together with routine fluid and electrolyte replacement ) were equally effective in reducing the duration of diarrhoea , vibrio excretion , and intravenous-fluid administration requiring close observation in cases of cholera . Furazolidone 400 mg . in a single dose was as effective as 100 mg . six-hourly , and no untoward effects were noted . For public-health purpose s , the single-dose regimen and low cost of furazolidone are advantages Doxycycline was compared with tetracycline in the treatment of cholera . Four types of treatment were compared : Group A was given 200 mg of doxycycline on admission and 100 mg on the second day ; Group B was given 200 mg of doxycycline on admission only ; Group C was given 300 mg of doxycycline on admission only ; and Group D received 500 mg of tetracycline every 6 h for 48 h. Tetracycline showed a slight advantage in respect of duration of diarrhoea and vibrio excretion compared with doxycycline given as a single dose of 300 mg , but fluid intake and output were about the same in these two groups . The other two doxycycline treatment schedules did not compare well with tetracycline treatment
Background Cholera is an acute watery diarrhoea caused by infection with the bacterium Vibrio cholerae , which if severe can cause rapid dehydration and death .
Effective management requires early diagnosis and rehydration using oral rehydration salts or intravenous fluids .
In this review , we evaluate the additional benefits of treating cholera with antimicrobial drugs .
Objectives To quantify the benefit of antimicrobial treatment for patients with cholera , and determine whether there are differences between classes of antimicrobials or dosing schedules .