OBJECTIVE: To assess the preventive role of zinc chloride on toxicity of ciprofloxacin administration in Wistar albino rat litter. It was a Prospective experimental study. The study was carried out in the Department of Anatomy, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi, Pakistan during March 2002 to February 2003 one year study. METHOD: Ciprofloxacin and zinc chloride were administered to newly born albino rat litters separately and simultaneously at a dose of 20 mg/kg body weight and 1200 microg/Kg body weight respectively, intraperitonealy twice daily from 1 - 14 day after birth. The animals were sacrificed by deep ether anaesthesia. The fore and hind limbs were dis-articulated from the axial skeleton, soft tissue was removed and bones were fixed in 10% buffered formalin. Decalcification was done in 10% nitric acid and 10% formic acid changes. After paraplast embedding, 4 microm thick longitudinal sections of proximal & distal ends of long bones were cut by a rotary microtome. Routine staining with haemotoxylin and eosin was performed. Histomorphometery was done to measure the thickness of epiphyseal cartilage and was compared with similar values of the control animals. The results were statistically analyzed to evaluate the significance. RESULT: Our study revealed that ciprofloxacin administration in new born albino rat litter decreased the width of epiphyseal growth plate cartilage by 13.7 +/- 0.42 microm, 10.43% in humerus and 6.6 +/- 1.2 microm 4.72% in femur as compared to control, whereas, simultaneous zinc chloride administration restricted the decrease to 1.27 microm +/- SD in humerus and 2.05 microm +/- SD in femur. CONCLUSION: Simultanous zinc chloride administration minimized the epiphseal cartilage damage induced by ciprofloxacin in Wistar albino rat litter.

Inappropriate antibiotic use for pulmonary infiltrates is common in the intensive care unit (ICU). We sought to devise an approach that would minimize unnecessary antibiotic use, recognizing that a gold standard for the diagnosis of nosocomial pneumonia does not exist. In a randomized trial, clinical pulmonary infection score (CPIS)(Pugin, J., R. Auckenthaler, N. Mili, J. P. Janssens, R. D. Lew, and P. M. Suter. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic "blind" bronchoalveolar lavage fluid. Am. Rev. Respir. Dis. 1991;143: 1121-1129) was used as operational criteria for decision-making regarding antibiotic therapy. Patients with CPIS </= 6 (implying low likelihood of pneumonia) were randomized to receive either standard therapy (choice and duration of antibiotics at the discretion of physicians) or ciprofloxacin monotherapy with reevaluation at 3 d; ciprofloxacin was discontinued if CPIS remained </= 6 at 3 d. Antibiotics were continued beyond 3 d in 90%(38 of 42) of the patients in the standard as therapy compared with 28%(11 of 39) in the experimental therapy group (p = 0.0001). In patients in whom CPIS remained </= 6 at the 3 d evaluation point, antibiotics were still continued in 96%(24 of 25) in the standard therapy group but in 0%(0 of 25) of the patients in the experimental therapy group (p = 0.0001). Mortality and length of ICU stay did not differ despite a shorter duration (p = 0.0001) and lower cost (p = 0.003) of antimicrobial therapy in the experimental as compared with the standard therapy arm. Antimicrobial resistance, or superinfections, or both, developed in 15%(5 of 37) of the patients in the experimental versus 35%(14 of 37) of the patients in the standard therapy group (p = 0.017). Thus, overtreatment with antibiotics is widely prevalent, but unnecessary in most patients with pulmonary infiltrates in the ICU. The operational criteria used, regardless of the precise definition of pneumonia, accurately identified patients with pulmonary infiltrates for whom monotherapy with a short course of antibiotics was appropriate. Such an approach led to significantly lower antimicrobial therapy costs, antimicrobial resistance, and superinfections without adversely affecting the length of stay or mortality.

CONTEXT: The optimal antimicrobial regimen and treatment duration for acute uncomplicated pyelonephritis are unknown. OBJECTIVE: To compare the efficacy and safety of a 7-day ciprofloxacin regimen and a 14-day trimethoprim-sulfamethoxazole regimen for the treatment of acute pyelonephritis in women. DESIGN: Randomized, double-blind comparative trial conducted from October 1994 through January 1997. SETTING: Twenty-five outpatient centers in the United States. PATIENTS: Of 378 enrolled premenopausal women aged at least 18 years with clinical diagnosis of acute uncomplicated pyelonephritis, 255 were included in the analysis. Other individuals were excluded for no baseline causative organism, inadequate receipt of study drug, loss to follow-up, no appropriate cultures, and other reasons. INTERVENTIONS: Patients were randomized to oral ciprofloxacin, 500 mg twice per day for 7 days (with or without an initial 400-mg intravenous dose) followed by placebo for 7 days (n = 128 included in analysis) vs trimethoprim-sulfamethoxazole, 160/800 mg twice per day for 14 days (with or without intravenous ceftriaxone, 1 g)(n = 127 included in the analysis). MAIN OUTCOME MEASURE: Continued bacteriologic and clinical cure, such that alternative antimicrobial drugs were not required, among evaluable patients through the 4- to 11-day posttherapy visit, compared by treatment group. RESULTS: At 4 to 11 days posttherapy, bacteriologic cure rates were 99%(112 of 113) for the ciprofloxacin regimen and 89%(90 of 101) for the trimethoprim-sulfamethoxazole regimen (95% confidence interval [CI] for difference, 0.04-0.16; P =.004). Clinical cure rates were 96%(109 of 113) for the ciprofloxacin regimen and 83%(92 of 111) for the trimethoprim-sulfamethoxazole regimen (95% CI, 0.06-0.22; P =.002). Escherichia coli, which caused more than 90% of infections, was more frequently resistant to trimethoprim-sulfamethoxazole (18%) than to ciprofloxacin (0%; P<.001). Among trimethoprim-sulfamethoxazole-treated patients, drug resistance was associated with greater bacteriologic and clinical failure rates (P<.001 for both). Drug-related adverse events occurred in 24% of 191 ciprofloxacin-treated patients and in 33% of 187 trimethoprim-sulfamethoxazole-treated patients, respectively (95% CI,-0.001 to 0.2). CONCLUSIONS: In our study of outpatient treatment of acute uncomplicated pyelonephritis in women, a 7-day ciprofloxacin regimen was associated with greater bacteriologic and clinical cure rates than a 14-day trimethoprim-sulfamethoxazole regimen, especially in patients infected with trimethoprim-sulfamethoxazole-resistant strains.

BACKGROUND. Hospitalization and intravenous (IV) broad-spectrum antibiotics are the standard of care for all febrile neutropenic patients with cancer. Recent work suggests that a low-risk population exists who might benefit from an alternate approach. METHODS. A prospective randomized clinical trial was performed comparing oral ciprofloxacin 750 mg plus clindamycin 600 mg every 8 hours with IV aztreonam 2 g plus clindamycin 600 mg every 8 hours for the empiric outpatient treatment of febrile episodes in low-risk neutropenic patients with cancer. RESULTS. The oral regimen cured 35 of 40 episodes (88% response rate), whereas the IV regimen cured 41 of 43 episodes (95% response rate, P = 0.19). Although the cost of the oral regimen was significantly less than that of the IV regimen (P < 0.0001), it was associated with significant renal toxicity (P < 0.05), which led to early termination of the study. Overall, combining its safety and efficacy, the IV regimen was superior (P = 0.03). CONCLUSIONS. This prospective study suggested that outpatient antibiotic therapy for febrile episodes in low-risk neutropenic patients with cancer is safe and effective. Better oral regimens are needed.

Metronidazole is effective for the treatment of acute pouchitis after ileal pouch-anal anastomosis, but it has not been directly compared with other antibiotics. This randomized clinical trial was designed to compare the effectiveness and side effects of ciprofloxacin and metronidazole for treating acute pouchitis. Acute pouchitis was defined as a score of 7 or higher on the 18-point Pouchitis Disease Activity Index (PDAI) and symptom duration of 4 weeks or less. Sixteen patients were randomized to a 2-week course of ciprofloxacin 1,000 mg/d (n = 7) or metronidazole 20 mg/kg/d (n = 9). Clinical symptoms, endoscopic findings, and histologic features were assessed before and after therapy. Both ciprofloxacin and metronidazole produced a significant reduction in the total PDAI score as well as in the symptom, endoscopy, and histology subscores. Ciprofloxacin lowered the PDAI score from 10.1+/-2.3 to 3.3+/-1.7 (p = 0.0001), whereas metronidazole reduced the PDAI score from 9.7+/-2.3 to 5.8+/-1.7 (p = 0.0002). There was a significantly greater reduction in the ciprofloxacin group than in the metronidazole group in terms of the total PDAI (6.9+/-1.2 versus 3.8+/-1.7; p = 0.002), symptom score (2.4+/-0.9 versus 1.3+/-0.9; p = 0.03), and endoscopic score (3.6+/-1.3 versus 1.9+/-1.5; p = 0.03). None of patients in the ciprofloxacin group experienced adverse effects, whereas three patients in the metronidazole group (33%) developed vomiting, dysgeusia, or transient peripheral neuropathy. Both ciprofloxacin and metronidazole are effective in treating acute pouchitis with significant reduction of the PDAI scores. Ciprofloxacin produces a greater reduction in the PDAI and a greater improvement in symptom and endoscopy scores, and is better tolerated than metronidazole. Ciprofloxacin should be considered as one of the first-line therapies for acute pouchitis.

OBJECTIVE: To describe the design and first-round survey results of a trial of intensive sexually transmitted disease (STD) control to reduce HIV-1 incidence. STUDY DESIGN: Randomized, controlled, community-based trial in Rakai District, Uganda. METHODS: In this ongoing study, 56 communities were grouped into 10 clusters designed to encompass social/sexual networks; clusters within blocks were randomly assigned to the intervention or control arm. Every 10 months, all consenting resident adults aged 15-59 years are visited in the home for interview and sample collection (serological sample, urine, and, in the case of women, self-administered vaginal swabs). Sera are tested for HIV-1, syphilis, gonorrhea, chlamydia, trichomonas and bacterial vaginosis. Following interview, all consenting adults are offered directly observed, single oral dose treatment (STD treatment in the intervention arm, anthelminthic and iron-folate in the control arm). Treatment is administered irrespective of symptoms or laboratory testing (mass treatment strategy). Both arms receive identical health education, condom and serological counseling services. RESULTS: In the first home visit round, the study enrolled 5834 intervention and 5784 control arm subjects. Compliance with interview, sample collection and treatment was high in both arms (over 90%). Study arm populations were comparable with respect to sociodemographic and behavioral characteristics, and baseline HIV and STD rates. The latter were high: 16.9% of all subjects were HIV-positive, 10.0% had syphilis, and 23.8% of women had trichomonas and 50.9% had bacterial vaginosis. CONCLUSIONS: Testing the effects of STD control on AIDS prevention is feasible in this Ugandan setting.

A combination of ciprofloxacin (intravenous then oral) and oral rifampicin was tested in 14 intravenous drug users with right-sided Staphylococcus aureus endocarditis. All 10 patients who completed therapy were cured based on resolution of symptoms and negative blood cultures at 4 weeks post therapy.

We collected data during postexposure antimicrobial prophylaxis campaigns and from a prophylaxis program evaluation 60 days after start of antimicrobial prophylaxis involving persons from six U.S. sites where Bacillus anthracis exposures occurred. Adverse events associated with antimicrobial prophylaxis to prevent anthrax were commonly reported, but hospitalizations and serious adverse events as defined by Food and Drug Administration criteria were rare. Overall adherence during 60 days of antimicrobial prophylaxis was poor (44%), ranging from 21% of persons exposed in the Morgan postal facility in New York City to 64% of persons exposed at the Brentwood postal facility in Washington, D.C. Adherence was highest among participants in an investigational new drug protocol to receive additional antibiotics with or without anthrax vaccine--a likely surrogate for anthrax risk perception. Adherence of <60 days was not consistently associated with adverse events.

The pharmacokinetics and tissue penetration of five quinolones were studied in volunteers. The compounds were norfloxacin (400 mg po), enoxacin (400 mg iv and 600 mg po), ciprofloxacin (100 mg iv and 500 mg po), ofloxacin (600 mg po) and pefloxacin (400 mg iv). Of the oral agents studied ofloxacin and ciprofloxacin were the most rapidly absorbed (Tmax = 1.2 h) and enoxacin the least (Tmax = 1.9 h). The serum levels attained were highest in the case of ofloxacin (after allowing for the higher dose administered). The serum half-lives were norfloxacin 3.75 h, ciprofloxacin 3.9 h (po), 4.0 h (iv), ofloxacin 7.0 h, enoxacin 6.2 h (po), 5.1 h (iv) and pefloxacin 10.5 h. All agents penetrated blister fluid readily. The 24 h urine recovery was 62% for oral enoxacin, 46.4% for iv enoxacin (plus 12.2% for oxo-enoxacin), 27% for norfloxacin, 30.6% for oral ciprofloxacin, 75.7% for iv ciprofloxacin, 73% for ofloxacin and 4.9% for pefloxacin (plus 9.2% for the norfloxacin metabolite and 17.8% for pefloxacin N-oxide).

The fluoroquinolones are promising new antituberculous agents. A randomized controlled trial of 200 adult patients with sputum smear-positive pulmonary tuberculosis was conducted in Tanzania. Patients received either a trial regimen (HRC) consisting of isoniazid (300 mg), rifampin (600 mg), and ciprofloxacin (750 mg) or a control regimen (HRZE) consisting of isoniazid (300 mg), rifampin (600 mg), pyrazinamide (25 mg/kg), and ethambutol (15 mg/kg). The 168 evaluable patients all had negative smears and cultures by month 6, but the time to conversion to negativity was longer for the HRC group than for the HRZE group because of the poor response of patients infected with human immunodeficiency virus (HIV) to the HRC regimen. Relapse was more frequent in the HRC group. The sterilizing activity of ciprofloxacin does not appear to be equal to that of the combination of pyrazinamide and ethambutol, but the difference in outcome was significant only among HIV-infected patients.

STUDY OBJECTIVE: To determine the steady-state plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) concentrations of levofloxacin and ciprofloxacin. DESIGN: Multiple-dose, open-label, randomized pharmacokinetic study. PARTICIPANTS: Thirty-six healthy, nonsmoking adult subjects were randomized either to oral levofloxacin, 500 or 750 mg once daily for five doses, or ciprofloxacin, 500 mg q12h for nine doses. INTERVENTIONS: Venipuncture, bronchoscopy, and BAL were performed in each subject at 4 h, 12 h, or 24 h after the last administered dose of antibiotic. MEASUREMENT AND RESULTS: Mean plasma concentrations of levofloxacin and ciprofloxacin were similar to those previously reported. For once-daily dosing of levofloxacin, 500 mg, the mean (+/- SD) steady-state concentrations at 4 h, 12 h, and 24 h in ELF were 9.9 +/- 2.7 microg/mL, 6.5 +/- 2.5 microg/mL, and 0.7 +/- 0.4 microg/mL, respectively; AM concentrations were 97.9 +/- 80.0 microg/mL, 36.7 +/- 23.4 microg/mL, and 13.8 +/- 16.0 microg/mL, respectively. For levofloxacin, 750 mg, the mean steady-state concentrations in ELF were 22.1 +/- 14.9 microg/mL, 9.2 +/- 5.3 microg/mL, and 1.5 +/- 0.8 microg/mL, respectively; AM concentrations were 105.1 +/- 65.5 microg/mL, 36.2 +/- 26.1 microg/mL, and 15.1 +/- 2.0 microg/mL, respectively. The concentrations of ciprofloxacin at 4 h and 12 h in ELF were 1.9 +/- 0.9 microg/mL and 0.4 +/- 0.1 microg/mL, respectively; AM concentrations were 34.9 +/- 23.2 microg/mL and 6.8 +/- 5.9 microg/mL, respectively. The differences in the ELF concentrations of the two levofloxacin groups vs those of the ciprofloxacin group were significant (p < 0.05) at each sampling time. CONCLUSIONS: Levofloxacin was more extensively distributed into intrapulmonary compartments than ciprofloxacin and achieved significantly higher steady-state concentrations in plasma and ELF during the 24 h after drug administration.