Eradication of nasopharyngeal carriage of Neisseria meningitidis in children and adults in rural Africa: a comparison of ciprofloxacin and rifampicin. Emergence of ciprofloxacin resistance in nosocomial methicillin-resistant Staphylococcus aureus isolates. Resistance during ciprofloxacin plus rifampin therapy for methicillin-resistant S aureus colonization. Ceftriaxone versus penicillin G in the short-term treatment of meningococcal meningitis in adults. A prospective randomized comparison of cefotaxime vs ampicillin and chloramphenicol for bacterial meningitis in children. Comparison of ceftriaxone and traditional therapy of bacterial meningitis. Ciprofloxacin versus ceftriaxone in the treatment of multiresistant typhoid fever. Comparison of the efficacy and safety of ceftriaxone to ampicillin/chloramphenicol in the treatment of childhood meningitis. Ceftriaxone compared with a combination of ampicillin and chloramphenicol in the treatment of bacterial meningitis in adults. Equivalence of ceftriaxone and rifampicin in eliminating nasopharyngeal carriage of serogroup B Neisseria meningitidis. A randomized study of ciprofloxacin versus ceftriaxone in the treatment of nursing home-acquired lower respiratory tract infections. Prevention of infectious complications after transjugular intrahepatic portosystemic shunt in cirrhotic patients with a single dose of ceftriaxone. [Evaluation of the sanative action of rifampicin on the meningococcal carrier state]. Evaluation of the efficacy of prophylactic intravenous antibiotherapy with ceftriaxone in post-chemotherapy agranulocytic patients. Trial of dexamethasone treatment for severe bacterial meningitis in adults. Adult Meningitis Steroid Group. Intraperitoneal ciprofloxacin and rifampicin versus cephradine as initial treatment of (C)APD-related peritonitis: a prospective randomized multicenter comparison (CIPPER trial). Efficacy of ciprofloxacin in enteric fever: comparison of treatment duration in sensitive and multidrug-resistant Salmonella. Multicenter, randomized trial of ciprofloxacin plus azlocillin versus ceftazidime plus amikacin for empiric treatment of febrile neutropenic patients. Oral ciprofloxacin vs. intramuscular ceftriaxone as empiric treatment of acute invasive diarrhea in children. Oral ciprofloxacin plus colistin: prophylaxis against bacterial infection in neutropenic patients. A strategy for the prevention of emergence of antimicrobial resistance. Rifampin does not improve the efficacy of quinolone antibacterial prophylaxis in neutropenic cancer patients: results of a randomized clinical trial. Prospective comparative trial of ceftriaxone vs. conventional therapy for treatment of bacterial meningitis in children.
A randomized comparative study of rifampicin and ciprofloxacin for eradicating nasopharyngeal carriage of meningococci was undertaken in Malawi. Of 1878 contacts of persons with meningococcal meningitis, 1875 were evaluatable for safety and efficacy of the drugs. Rifampicin was given to 836 contacts, ciprofloxacin to 711, and ceftriaxone to 328 (children < 2 years old or pregnant or lactating women). One and 2 weeks after therapy, side effects in those given rifampicin and ciprofloxacin were not significantly different. In the ciprofloxacin group, with 470 subjects < 18 years old, only one event (mild abdominal pain) occurred that was related to the drug. Nasopharyngeal carriage was detected in 88 (10.5%) of those given rifampicin, 79 (11.1%) given ciprofloxacin, and 41 (12.5%) given ceftriaxone. Eradication rates after 1 and 2 weeks of treatment, respectively, were 96.5% and 97.7% for rifampicin, 88.6% and 91.1% for ciprofloxacin, and 95.1% and 97.6% for ceftriaxone. Ciprofloxacin provides a safe and effective alternative to rifampicin for eradication of meningococcal carriage in children 2-18 years old. We initiated a randomized, single-blinded trial of ciprofloxacin plus rifampin vs sulfamethoxazole and trimethoprim plus rifampin in the therapy for patients who underwent colonization with methicillin-resistant Staphylococcus aureus (MRSA). Patients who were colonized with MRSA received 2 weeks of either regimen. The study was terminated after the enrollment of 21 subjects due to the recognition of ciprofloxacin resistance in 10 of 21 new MRSA isolates during the last 2 months of the study. Five of the 10 patients with ciprofloxacin-resistant MRSA isolates had never received ciprofloxacin. Long-term (6-month) eradication had been achieved in only three of 11 ciprofloxacin plus rifampin and four of 10 sulfamethoxazole and trimethoprim plus rifampin recipients. The use of this new fluoroquinolone for the eradication of MRSA colonization is usually not effective and may risk the development of ciprofloxacin resistance in MRSA within the hospital environment. Short-term treatment with ceftriaxone 2 g once daily for two days (group 1) was compared to treatment with a standard regimen of penicillin G (group 2) for six days in adults with meningococcal meningitis. Thirty-six patients were allocated in a randomized fashion to a treatment group: 16 to group 1 and 20 to group 2. The clinical and microbiological results were comparable in the two treatment groups. In both groups cultures of cerebrospinal fluid were sterile after 24 hours. One patient in each group died. In group 1 one case of fulminant meningococcemia and one case of brain abscess required further antibiotic treatment. It is concluded that short-term treatment with ceftriaxone is feasible but patients with severe forms of meningitis would not be eligible for treatment with this regimen, and careful follow-up of the patients receiving ceftriaxone is necessary. Fifty children with bacterial meningitis were prospectively randomized to receive cefotaxime (50 mg/kg/dose every 6 hours) or ampicillin and chloramphenicol in standard doses. Twenty-three patients received cefotaxime and 27 received standard therapy. Bacterial isolates included: Haemophilus influenzae (29), Streptococcus pneumoniae (eight), Neisseria meningitidis (eight), group B streptococci (three), and Salmonella enteritidis (two). Ten (34%) of the H. influenzae isolates were resistant to ampicillin, nine on the basis of beta-lactamase production. All strains were susceptible to cefotaxime. Clinical cure rates for the cefotaxime (100%) and standard therapy (96%) groups were similar; survival without detectable sequelae was similar, at 78% and 77%, respectively. The duration of therapy, 11.1 +/- 2.4 days (range 10 to 21 days) vs 11.9 +/- 3.9 days (range 10 to 21 days), and days to defervescence, 4.7 +/- 2.6 days (range 1 to 14 days) vs 5.6 +/- 2.9 days (range 2 to 17 days), were similar in the cefotaxime and standard therapy groups, respectively. No adverse drug reactions or side effects were noted in either group. Cefotaxime was found to be as safe and effective as standard therapy for the treatment of bacterial meningitis in children. Forty-five children (aged 1 day to 15 years) with bacterial meningitis were randomized to receive either traditional therapy (ampicillin and chloramphenicol or gentamicin, pending sensitivity) or ceftriaxone (100 mg/kg per day in two doses for a minimum of 10 days). The etiological agents involved were similar for the two groups and included Haemophilus influenzae type b, Neisseria meningitidis, Streptococcus pneumoniae, and group B streptococcus. Repeat spinal taps were carried out 24 to 48 h after admission. Organisms were seen on the Gram stain of one patient treated with ceftriaxone, but five patients in the traditional therapy group had organisms present on Gram stain of uncentrifuged spinal fluid or positive cultures of the spinal fluid (or both). Ceftriaxone entered the cerebrospinal fluid well, and the average cerebrospinal fluid bactericidal activity for ceftriaxone 1 h after a dose was at least 60 times greater than for ampicillin or chloramphenicol. In those patients who received treatment for a long enough period of time to permit evaluation, there was one death in each group, both due to S. pneumoniae. The length of fever and complications were similar for the patients in both groups. Ceftriaxone was well tolerated; diarrhea, seen in 5 of the 22 patients who received the drug, was the most commonly encountered adverse effect. It was mild, and in no case was it necessary to discontinue the drug. Ceftriaxone appears in this preliminary study to be a safe and acceptable single agent for the treatment of bacterial meningitis in children. A randomized trial comparing ceftriaxone (3 g given parenterally per day for 7 days) to ciprofloxacin (500 mg given orally twice a day for 7 days) in the treatment of blood culture positive typhoid fever was conducted. Twenty patients were openly randomized to receive ciprofloxacin and 22 to receive ceftriaxone. The outcome was classified as clinical failure in 6 patients (27%) in the ceftriaxone group, but in none in the ciprofloxacin group (p = 0.01). The mean duration of fever was four days in the ciprofloxacin group and about five days in the ceftriaxone group (p = 0.04). In the six patients in the ceftriaxone group who experienced failure, therapy was switched to ciprofloxacin and the patients became afebrile and asymptomatic within 48 hours. Patients with resistant strains of Salmonella typhi and patients with sensitive strains responded equally well to ciprofloxacin therapy. Analysis of a subset of 12 of the multiresistant strains revealed that resistance was encoded for by a transferable 180 kilobase plasmid. Ciprofloxacin represents a useful treatment option in areas where multiresistant strains are likely to be encountered. Ceftriaxone is a new cephalosporin with a broad spectrum of antibacterial activity and unique serum and CSF pharmacokinetics. The drug was compared in a randomized fashion with ampicillin and chloramphenicol in the treatment of 19 children with Haemophilus influenzae type b meningitis. Ceftriaxone was also administered non-randomly to six other patients including three children with Gram-negative meningitis. Among the children with H. influenzae meningitis, no deaths were noted and the outcomes of the study and the control groups were similar. Ninety per cent of the isolates of H. influenzae were inhibited by 0.0625, 1 and 1 mg/l of ceftriaxone, ampicillin and chloramphenicol respectively. One child with pneumococcal meningitis and two children with meningococcal meningitis recovered rapidly and without incident during ceftriaxone therapy. Three children with Gram-negative meningitis caused by multiply-drug resistant organisms were bacteriologically cured within five days of the onset of therapy. Persistent pleocytosis and neurological disabilities were noted in two at the conclusion of therapy. Ceftriaxone, as a single agent, was comparable in efficacy with traditional antimicrobial therapy usually employed in childhood meningitis. Thirty patients, 25 males and 5 females, aged 16-30 years (mean 21.8 years) with bacterial meningitis were assigned randomly into one of two therapeutic regimens. Patients in Group I received ceftriaxone 100 mg/kg (max 4 g) intravenously (i.v.) once daily. Those in Group II received ampicillin i.v. 160 mg/kg/day plus chloramphenicol i.v. 100 mg/kg/day every 6 h. Of the 15 patients in Group I, N. meningitidis was isolated from 11 patients and S. pneumoniae from 4; and of the 15 patients in Group II, N. meningitidis was isolated from 10 patients and S. pneumoniae from 5. Response to therapy as measured by mortality, time taken for defervescence and for patients to regain full consciousness were comparable in the two groups. One patient in each group died; both died within 24 h of initiation of therapy. The mean no. of days taken to become afebrile were 3.4 and 3.5 and to regain full consciousness were 3.9 and 3.5 for Groups I and II respectively. Ceftriaxone given i.v. appears to be as effective as a combination of ampicillin and chloramphenicol in the treatment of adult patients with meningitis due to N. meningitidis and S. pneumoniae. However, the once-daily schedule of ceftriaxone is more convenient, saving nursing time and expense. The efficacy of ceftriaxone in eliminating nasopharyngeal carriage of Neisseria meningitidis was compared with that of rifampicin during an epidemic of serogroup B meningococcal disease in Auckland, New Zealand. Household contacts of cases had a throat swab taken and were randomized to treatment. Carriers had a repeat swab taken 6 days later to determine efficacy of treatment. Ceftriaxone (98.2%) was equivalent to rifampicin (97.6%) in eliminating serogroup B N. meningitidis. It is cheaper than rifampicin and has the advantage of full compliance and fewer contraindications, but its acceptability by patients may limit its use as a first-line prophylactic agent. To compare the efficacy and safety of ciprofloxacin and ceftriaxone in patients with nursing home-acquired lower respiratory tract infections requiring initial hospitalization.
                Prospective, randomized trial.
                Extended care nursing homes affiliated with a teaching hospital.
                Fifty patients aged 60 years or older with normal or mildly impaired renal function admitted to the hospital for treatment of lower respiratory tract infections.
                Twenty-four patients received initial therapy with intravenous ciprofloxacin, 200 mg every 12 hours (19 patients) or 400 mg every 12 hours (5 patients) during the acute phase followed by 750 mg orally every 12 hours during the convalescence phase. Twenty-six patients received initial therapy with intravenous ceftriaxone, 2 g every 24 hours during the acute phase followed by 1 g administered intramuscularly every 24 hours during the convalescent phase. The total duration of therapy was 14 days.
                Successful outcome was defined as resolution or marked improvement in clinical signs and symptoms of lower respiratory tract infection upon completion of the treatment course.
                Twelve (50%) of the ciprofloxacin-treated and 14 (54%) of ceftriaxone-treated patients had successful outcomes. Recurrent oropharyngeal aspiration was the reason for treatment failure in most patients refractory to either antibiotic. Mortality during therapy was 8% in each group. From 21 satisfactory sputum specimens collected, S. pneumoniae was the most common isolate, followed by H. influenzae and other Gram-negative bacteria. Ciprofloxacin therapy was well tolerated; ceftriaxone therapy was discontinued in two patients (8%) due to adverse reactions (intramuscular pain and drug fever).
                Sequential intravenous/oral ciprofloxacin appears to be as safe and effective as sequential intravenous/intramuscular ceftriaxone. The optimal dosage of intravenous ciprofloxacin in this patient population appears to be 400 mg every 12 hours; however, additional clinical and pharmacokinetic studies with this regimen are warranted. Patients with cirrhosis of the liver are prone to bacterial infections. Therapeutic interventions such as endoscopic sclerotherapy increase the risk of bacterial infections in these patients. Following insertion of a transjugular intrahepatic portosystemic shunt (TIPS), the incidence of severe bacterial infections was recently shown to be 20% after elective procedures. This finding suggests antibiotic prophylaxis with the TIPS procedure. Antibiotic prophylaxis using cefotiam or cefotaxime/ampicillin did not significantly reduce infectious complications. The aim of the present study was therefore to investigate the efficacy of two different doses of a long-acting cephalosporin in prevention of bacterial infection after TIPS.
                Eighty-two patients with cirrhosis (age: 52 +/- 2 years) who underwent elective TIPS were randomized to receive a single i.v. dose of either 1 g or 2 g Ceftriaxone 1 hour before the intervention. Patients with evidence of or suspected infections and patients on antibiotic therapy within 7 days prior to TIPS were excluded. Body temperature was monitored t.i.d. for 1 week and white blood count (WBC) and C-reactive protein (CRP) were determined before TIPS and 1 day and 1 week after TIPS.
                Only 2 of 82 patients (2.6%) showed signs of infection following TIPS insertion: One of 40 patients receiving 1 g Ceftriaxone and 1 of 42 patients receiving 2 g Ceftriaxone prior to TIPS developed temperature > 38.5 degrees C. In the latter patient this was due to pneumonia. This patient received antibiotic treatment with imipenem for 10 days. Temperature in the other patient normalized within 12 hours and he did not require antibiotic treatment. No significant differences in temperature, WBC and CRP between the different doses of Ceftriaxone were observed.
                Prophylactic treatment with Ceftriaxone reduces the reported incidence of bacterial infections after TIPS in patients with cirrhosis of the liver. Prophylaxis with 1 g Ceftriaxone seems as efficacious as 2 g. The results of the epidemiological control experiment on the efficacy of rifampicin in sanation of meningococci carriers are presented. The preliminary study of rifampicin sensitivity of 41 freshly isolated nasopharyngeal meningococcal strains showed that the MIC of the drug for 63 per cent of the isolates was 0.04--0.1 gamma/ml. Sanation was performed for 2 days; 1.2 g of the drug was used during the treatment course. The results of examination of 91 meningococci carriers showed that 4 days after the sanation the specific weight of the persons isolating no meningococci was reliably higher in the experimental group than that in the control group. The coefficient of rifampicin efficiency was 70.8 per cent. 10 days after sanation the difference in the level of the carriers isolating no meningococci in the experimental and the control groups was statistically insignificant. Therefore, the carriers treated with the drug received temporary protection from the causative agent at an average for 1 week. Later on they could become carriers again. As a result of sanation no changes in the meningococcal sensitivity to rifampicin was observed. A prospective study was carried out in 44 patients treated by intensive chemotherapy inducing a prolonged neutropenia (granulocytes less than 0.5.10(9)/l). All the patients were isolated in protected rooms, received a pathogen-free diet and nonabsorbable oral antibiotics. After double-blind randomization, 22 patients received 2 g of Ceftriaxone (Cef) in a daily infusion beginning on the first day of chemotherapy; and 22 patients received 2 g of placebo (P) under the same conditions. Prophylaxis was continued until the neutropenia resolved (granulocytes greater than 0.5.10(9)/l) or until the onset of infectious symptoms. 19 patients in each group developed febrile episodes, occurring significantly later in the Cef group (16.6 days versus 10.6 days in the P group). No Cef-resistant organism was isolated. Finally, the time at which apyrexia was obtained after the beginning of curative antibiotherapy was the same in both groups. The routine intravenous administration of Cef in combination with nonabsorbable antibiotics is a useful approach in reducing the risk of infection in the neutropenic host. To evaluate the clinical benefit of early adjunctive dexamethasone therapy for severe bacterial meningitis in adults.
                Multicenter, double-blind, randomized trial initiated in emergency or intensive care units in France and Switzerland. Within 3 h after initiation of an aminopenicillin therapy, patients received dexamethasone (10 mg q.i.d.) or placebo for 3 days. The primary end-point was the rate of patients cured without any neurologic sequelae on day 30.
                Sixty patients were enrolled, predominantly with a severe form since 85% required ICU stay and 43% mechanical ventilation. Streptococcus pneumoniae accounted for 31 cases and Neisseria meningitidis for 18 cases. The study had to be stopped prematurely because of a new national recommendation of experts to use third generation cephalosporin and vancomycin as a result of the increasing rate of penicillin-resistant S. pneumoniae in France. After the third sequential analysis by the triangular statistical test, the difference of rate of cured patients without any neurologic sequelae was not statistically significant (p = 0.0711) between the dexamethasone group (74.2%; n = 31) and the placebo group (51.7%; n = 29). Furthermore, the former group was younger and less sick at inclusion.
                Bacterial meningitis is still a severe disease in adults, since the overall observed rate of death or severe neurologic sequelae was 26.7%. The reported data are inconclusive regarding a systematic use of dexamethasone as an adjunctive therapy for bacterial meningitis in adults. Moreover this treatment impairs antibiotic penetration into the cerebrospinal fluid (CSF) that can lead to therapeutic failure, particularly in areas with high or increasing rates of penicillin-resistant S. pneumoniae. The initial treatment of peritonitis has evolved from single-agent to combination regimens. The initial response rates improved with these newer regimens but relapsing peritonitis continues to occur. For biofilm-embedded or intracellularly sequestrated bacteria, a combination of intracellularly- and biofilm-active agents such as ciprofloxacin and rifampicin might be beneficial. Many Dutch centers continue to use cephradine as initial treatment, claiming clinically adequate responses with this regimen. We compared the impact of these two regimens on outcome in patients who developed a new episode of peritonitis.
                Prospective randomized open trial.
                Multicenter study including 14 Dutch dialysis units.
                From October 1996 to October 1999, 367 patients from 14 centers were randomized to be treated with ciprofloxacin + rifampicin (CR; each 50 mg/L) or cephradine (C; 250 mg/L) in case of peritonitis. Of these 367 patients, 98 developed peritonitis, 44 of whom were treated with CR and 54 with C.
                Clinical response, divided into early (during the 2 weeks of therapy) and late (including the following 4 weeks) response. Success was defined as disappearance of all signs and symptoms by days 4-6, through day 42. Bacteriological response was either success (eradication) or failure (persistence, superinfection, or eradication with relapse/reinfection).
                The groups were comparable for age, sex, duration of continuous ambulatory/automated peritoneal dialysis, and occurrence of diabetes. Bacteriological cultures in both groups revealed predominantly gram-positive micro-organisms. Initial and late clinical successes were obtained in 27/54 and 20/54 episodes (50% and 37%) in the C group, and 33/44 and 28/44 episodes (75% and 63.6%) in the CR group (p = 0.021 and p = 0.019). Bacteriological success occurred in 29.6% in the C group, and in 59.1% in the CR group (p= 0.026), with failure in 46.3% and 18.2%, respectively. Peritonitis episodes were bacteriologically not evaluable in 24.1% of episodes in the C group and 22.7% of episodes in the CR group, due mostly to no growth in the initial culture.
                The CIPPER Trial showed ciprofloxacin + rifampicin to be superior to cephradine as empiric treatment of peritonitis. The efficacy of two regimens of ciprofloxacin was compared in a randomized study conducted on 69 patients with enteric fever, 52.2% of whom had infection with multidrug-resistant (MDR) strains of Salmonella typhi or S. paratyphi. Patients were randomly assigned to two regimens (10 days versus 14 days) of ciprofloxacin (500 mg twice a day). The mean +/- SD time required for defervescence was similar for both regimens (4.2 +/- 1.9 days in the 10-day group and 4.9 +/- 2.6 days in the 14-day group). A 100% cure was observed in each treatment group and no serious side effects were observed. Relapse occurred in two patients (14-day regimen). Only one patient (14-day regimen) had growth of S. typhi in stool culture at the time of the first follow-up three days after completion of therapy. Follow-up studies on available patients on two, six, and 12 months after completion of therapy revealed that all patients had negative stool cultures for S. typhi and S. paratyphi. This study indicates that ciprofloxacin may be recommended as an initial therapy for enteric fever for adult men and nonpregnant and nonlactating women in areas where MDR strains of S. typhi and S. paratyphi are prevalent, and that 500 mg twice a day of the drug given for 10 days is as effective as 14 days at the same dosage. In a multicenter, randomized clinical trial, the efficacy of ciprofloxacin plus azlocillin was compared with that of a standard regimen of ceftazidime plus amikacin for the initial empiric treatment of fever in neutropenic cancer patients. In addition, the efficacy of early conversion from intravenous therapy to orally administered ciprofloxacin was compared with that of continued ceftazidime plus amikacin. Seventy-one oncology patients with 79 episodes of fever and neutropenia were randomly assigned to receive initial empiric antibiotic therapy with either intravenously administered ciprofloxacin and azlocillin followed by orally administered ciprofloxacin (regimen 1, 25 episodes); ceftazidime and amikacin (regimen 2, 30 episodes); or ceftazidime and amikacin followed by oral ciprofloxacin (regimen 3, 24 episodes). Microbiologically documented infections were the cause of fever in 10 (40 percent), seven (23 percent), and nine (38 percent) episodes in regimens 1, 2, and 3, respectively, including six, five, and four episodes of bacteremia. Patient survival was 90 to 92 percent in each regimen; however, some modification of antimicrobial therapy occurred in 65, 44, and 41 percent of surviving patients in regimens 1, 2, and 3, respectively. The rate of clearance of initial bacteremia was 67 percent (four of six) in regimen 1, 100 percent (five of five) in regimen 2 and 50 percent (two of four) in regimen 3. Patients in regimens 1 and 3 were able to convert to orally administered ciprofloxacin in 32 (65 percent) of 49 episodes after a mean of six days of intravenous therapy. Superinfections occurred in 24, 10, and 12 percent of patients receiving regimens 1, 2, and 3, respectively, and occurred similarly for patients receiving orally administered ciprofloxacin, 12 percent (four of 32), and intravenous therapy, 17 percent (eight of 47). Parenteral ciprofloxacin was generally well tolerated. One (4 percent) of 25 patients receiving regimen 1 experienced oto- or nephrotoxicity, compared with eight (15 percent) of 54 patients receiving regimens 1, 2, and 3 (p = 0.15), including three patients who required premature termination of aminoglycoside therapy. Our data suggest that the combination of ciprofloxacin and azlocillin is an effective alternative to ceftazidime and amikacin for the initial empiric therapy of febrile neutropenic patients, is generally well tolerated, and avoids the oto- and nephrotoxicity associated with aminoglycoside use. In addition, a majority of patients could change to orally administered ciprofloxacin alone after six days of parenteral therapy. Acute invasive diarrhea is a potentially serious condition in children. Because of the increasing resistance of enteric pathogens to commonly used oral antibiotics, intramuscular ceftriaxone has become the routine drug in the treatment of acute invasive diarrhea requiring an emergency visit in southern Israel. The inconvenience of this parenteral regimen created an increased need for oral pediatric formulations for the treatment of invasive diarrhea.
                To evaluate the efficacy and safety of a suspension formulation of ciprofloxacin in the treatment of acute invasive diarrhea in infants and children.
                From July 1996 through December 1997, 201 evaluable children ages 6 months to 10 years (35% <1 year; 70% <3 years) presenting with acute invasive diarrhea at the Pediatric Emergency Room were randomized to receive either ciprofloxacin suspension (10 mg/kg twice a day + im placebo; n = 95) or im ceftriaxone (50 mg/kg/day + placebo suspension; n = 106) for 3 days in a double blind manner. Stool cultures for Shigella, Salmonella, Campylobacter spp. and diarrheagenic Escherichia coli were obtained on Days 1, 3, 4 to 5 and 21 +/- 5. Clinical response and safety were assessed on Days 1, 2, 3, 4 to 5 and 21 +/- 5.
                We isolated 127 pathogens from 121 (60%) patients: 73 (57%) Shigella; 23 (18%) Salmonella; 18 (14%) E. coli; and 13 (10%) Campylobacter. Overall bacteriologic eradication on Day 4 to 5 was 99% for Shigella, 77% for Salmonella and 77% for Campylobacter, with no difference between the 2 groups. Clinical cure or improvement was observed in 100 and 99% of the ciprofloxacin and ceftriaxone groups, respectively. Serum ciprofloxacin values determined on Day 3 of the treatment were higher in the majority of patients than were the MIC50 and MIC90 values for the Shigella and Salmonella spp. isolated. Possible drug-related adverse events occurred in 13 patients [ciprofloxacin, 8 (8%); ceftriaxone, 5 (4.7%)] and were mild and transient. Joint examination was normal during and after completion of therapy in all patients.
                Oral ciprofloxacin was as safe and effective as intramuscular ceftriaxone for the empiric treatment of acute invasive diarrhea in ambulatory pediatric patients requiring an emergency room visit. Following a 2-year study, the combination of oral ciprofloxacin and colistin has been used continuously for 10 years without the emergence of resistance. During a 2-year period (1987-1989), we compared ciprofloxacin + colistin (CIP + COL) with neomycin + colistin (NEO + COL) in a randomized trial--combinations chosen because of the potential for prophylaxis of Gram-negative infection by ciprofloxacin, with colistin given to reduce the risk of emergence of resistance. Sixty-four patients with similar demographics in each arm were evaluable for efficacy analysis. Patients on CIP + COL had a significantly lower proportion of neutropenic days with fever (P < 0.001) and neutropenic days on intravenous antibiotics (P < 0.001) than patients on NEO + COL. A total of 54 (15 bacteriologically documented) pyrexial episodes occurred in patients on CIP + COL and 77 (41 bacteriologically documented) in patients on NEO + COL. Only two Gram-negative bacterial infections occurred in the CIP + COL arm compared with 16 in the NEO + COL arm. No Staphylococcus aureus infections occurred in the CIP + COL group compared with 10 in the other patients. Two CIP-resistant Gram-negative bacilli were isolated from patients on CIP + COL compared with 13 NEO-resistant Gram-negative bacilli from patients on NEO + COL. Following a subsequent decade of unchanged use of this prophylactic strategy in neutropenic patients, a 2-year follow-up study between 1 January 1998 and 31 December 1999 showed 66 significant infections during 700 [corrected] neutropenic episodes. Thirty-five of the 111 (31%) isolates were ciprofloxacin-resistant, involving 5% of the neutropenic episodes [corrected]. To determine whether the addition of rifampin to a quinolone-based antibacterial prophylactic regimen in patients undergoing high-dose chemotherapy (HDC) with peripheral-blood stem-cell transplantation (PBSCT) decreases the incidence of neutropenia and fever, Gram-positive bacteremia, and infection-related morbidity.
                Patients with solid tumors undergoing HDC with PBSCT were randomized to receive prophylactic antibiotics with either ciprofloxacin 500 mg orally every 8 hours or the same ciprofloxacin regimen with rifampin 300 mg orally every 12 hours. Prophylaxis was started 48 hours before stem-cell reinfusion. Patients were monitored to document the occurrence of neutropenia and fever, incidence and cause of bacterial infection, time to onset and duration of fever, requirement for intravenous antimicrobials, and length of hospital admission.
                Sixty-five patients were randomized to receive ciprofloxacin and 65 to receive ciprofloxacin plus rifampin, and from these groups, 62 and 61 were assessable, respectively. The proportion of patients who developed neutropenia and fever was 87% in the group treated with ciprofloxacin and 78% in the group treated with ciprofloxacin and rifampin (P =.25). Although there was a trend toward a reduction in the overall incidence of bacteremia (12 v 4 patients), and Gram-positive bacteremia (8 v 2 patients) with the addition of rifampin, none of these comparisons was statistically significant (P =.05 and P =.09, respectively).
                The results of this study, which demonstrate that rifampin does not improve ciprofloxacin antibacterial prophylaxis in cancer patients undergoing HDC with PBSCT support but that it does increase the occurrence of undesirable side effects, do not support the routine use of rifampin in this setting. Fifty children with bacterial meningitis were prospectively evaluated in a randomized comparative trial of twice daily ceftriaxone with conventional ampicillin and chloramphenicol therapy. The groups were comparable in age, sex, days of illness before admission, severity of illness at admission, etiology and admission cerebrospinal fluid (CSF) parameters and bacterial colony counts. The pathogens were Haemophilus influenzae type b (34 beta-lactamase-negative, 8 beta-lactamase-positive); Streptococcus pneumoniae (4); Neisseria meningitidis (3); and Streptococcus agalactiae (1). Initial CSF colony counts ranged from 2.5 X 10(2) to 1 X 10(10) colony-forming units/ml. In 44 children a lumbar puncture was repeated 10.5 to 18 hours after starting treatment; 16 of 24 (67%) ceftriaxone patients and 12 of 20 (60%) conventional therapy patients had sterile cultures. The reduction in the CSF bacterial colony counts (6.3 log10 colony-forming units/ml) was similar in both groups. Ceftriaxone CSF levels ranged from 1.0 to 8.0 micrograms/ml, representing a mean CSF penetration of 11.3% (range, 3.0 to 24.5%) of the simultaneous serum concentration. The median ceftriaxone bactericidal titer in CSF was 1:1024 compared with 1:4 achieved with conventional therapy. There were no significant differences in clinical responses or in frequency of complications, except for diarrhea which occurred in 59% of the ceftriaxone group and in 22% of the other (P less than 0.01). Despite one H. influenzae type b relapse occurring in the ceftriaxone group, ceftriaxone appears to be safe and as effective as conventional therapy for bacterial meningitis in children older than 2 months of age.
Using rifampin during an outbreak may lead to the circulation of resistant isolates. Use of ciprofloxacin, ceftriaxone or penicillin should be considered. All four agents were effective for up to two weeks follow up, though more trials comparing the effectiveness of these agents for eradicating N. meningitidis would provide important insights.