Determinants of bacteriological outcomes in exacerbations of chronic obstructive pulmonary disease.

PURPOSE: Changes in sputum microbiology following antibiotic treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), including patterns of bacteriological relapse and superinfection are not well understood. Sputum microbiology at exacerbation is not routinely performed, but pathogen presence and species are determinants of outcomes. Therefore, we determined whether baseline clinical factors could predict the presence of bacterial pathogens at exacerbation. Bacterial eradication at end of treatment (EOT) is associated with clinical resolution of exacerbation. We determined the clinical, microbiological and therapeutic factors that were associated with bacteriological eradication in AECOPD at EOT and in the following 8 weeks. METHODS: Sputum bacteriological outcomes (i.e., eradication, persistence, superinfection, reinfection) from AECOPD patients (N = 1352) who were randomized to receive moxifloxacin or amoxicillin/clavulanate in the MAESTRAL study were compared. Independent predictors of bacterial presence in sputum at exacerbation and determinants for bacteriological eradication were analyzed by logistic regression and receiver operating characteristic (ROC) analyses. RESULTS: Significantly greater bacteriological eradication with moxifloxacin was mainly driven by superior Haemophilus influenzae eradication (P = 0.002, EOT). Baseline clinical factors were a weak predictor of the presence of pathogens in sputum (AUCROC = 0.593). On multivariate analysis, poorer bacterial eradication was associated with antibiotic resistance (P = 0.0001), systemic steroid use (P = 0.0024) and presence of P. aeruginosa (P = 0.0282). CONCLUSIONS: Since clinical prediction of bacterial presence in sputum at AECOPD is poor, sputum microbiological analysis should be considered for guiding antibiotic therapy in moderate-to-severe AECOPD, particularly in those who received concomitant systemic corticosteroids or are at risk for infection with antibiotic-resistant bacteria.

Complicated urinary tract infections treated with extended-release ciprofloxacin with emphasis on Pseudomonas aeruginosa.

This report focuses on the role of Pseudomonas aeruginosa in complicated urinary tract infections in a prospective, open-label, multicenter study designed to evaluate the safety and efficacy of extended-release ciprofloxacin (ciprofloxacin XR) 1000 mg once daily for 7-14 days for the treatment of complicated urinary tract infections. A total of 204 patients were valid for intention-to-treat analysis, of whom 130 were included in the clinical efficacy population. In the 56 microbiologically valid patients the bacteriological eradication rate was 82.1% and the clinical cure rate was 94.6%. Patients with P. aeruginosa infections valid for microbiological efficacy (n = 7) had 100% bacteriological eradication and clinical cure rates. In the intention-to-treat population, the bacteriological and clinical cure rates were 42.1% (51/121) and 55.9% (114/204), respectively. These rates were 58.3% and 75.0% respectively, for patients with P. aeruginosa infections. To achieve the desired 10 patients with P. aeruginosa for analysis, these data were pooled with data from a previous study. Treatment failure correlated with pre-therapy P. aeruginosa isolates being resistant to ciprofloxacin. On exploratory multivariate regression analysis, presence of neurogenic bladder, urinary retention owing to benign prostatic hypertrophy, prior urinary tract infection, and ischemic heart disease predicted P. aeruginosa infection.

Eradication of H. influenzae in AECB: A pooled analysis of moxifloxacin phase III trials compared with macrolide agents.

Haemophilus influenzae is the most common bacterial pathogen associated with acute exacerbations of chronic bronchitis (AECB). This study determined the rate of bacterial eradication of H. influenzae during AECB treated with either macrolides or moxifloxacin. Adult AECB patients with H. influenzae were included in a pooled analysis of four double-blind, multicentre, randomised trials. Patients received either moxifloxacin (400 mg qd for 5-10 days) or macrolides (azithromycin 500 mg/250 mg qd for 5 days or clarithromycin 500 mg bid for 5-10 days). Bacterial eradication and clinical success were recorded at the test-of-cure visit (7-37 days post-therapy). Of 2555 patients in the intent-to-treat population, 910 were microbiologically valid and 292 (32%) had H. influenzae cultured at baseline. Bacterial eradication of H. influenzae was significantly higher with moxifloxacin vs. macrolide-treated patients (93.0% [133/143] vs. 73.2% [109/149], respectively, P = 0.001). Moxifloxacin also demonstrated higher eradication rates compared with azithromycin (96.8% vs. 84.6%, P = 0.019) and clarithromycin (90.1% vs. 64.2%, P = 0.001) analysed separately. Clinical success was 89.5% (128/143) for moxifloxacin vs. 85.2% (127/149) for the macrolide group (P = 0.278); similar results were found when moxifloxacin was compared individually with each macrolide. For patients with AECB due to H. influenzae, moxifloxacin provided superior bacterial eradication rates than macrolide therapy.

Efficacy of moxifloxacin for treatment of penicillin-, macrolide- and multidrug-resistant Streptococcus pneumoniae in community-acquired pneumonia.

This pooled analysis of six prospective, multicentre trials aimed to determine the efficacy of moxifloxacin in community-acquired pneumonia (CAP) due to penicillin-, macrolide- and multidrug-resistant Streptococcus pneumoniae (MDRSP). At a central laboratory, isolates were identified and antimicrobial susceptibility determined (microbroth dilution). MDRSP was defined as resistance > or =3 drug classes. Patients received oral or sequential intravenous/oral 400 mg moxifloxacin once daily for 7-14 days. The primary endpoint was clinical success at test-of-cure for efficacy-valid patients with proven pretherapy S. pneumoniae infection. Of 140 S. pneumoniae isolated (112 respiratory, 28 blood), 23 (16.4%) were penicillin resistant, 26 (18.6%) macrolide resistant and 31 (22.1%) MDRSP. The moxifloxacin MIC90 was 0.25 microg/ml. Clinical cure with moxifloxacin was 95.4% (125/131) overall, and 100% (21/21) for penicillin-, 95.7% (22/23) for macrolide- and 96.4% (27/28) for multidrug-resistant strains. Moxifloxacin provided excellent clinical and bacteriological cure rates in CAP due to drug-resistant pneumococci.

Efficacy and safety of sequential moxifloxacin for treatment of community-acquired pneumonia associated with atypical pathogens.

In two prospective, randomized studies intravenous (IV)/oral (PO) moxifloxacin (400 mg q.i.d.) was compared to IV/PO antimicrobial comparator agents for the treatment of hospitalized patients with community-acquired pneumonia. Reported here are the pooled data for the sub-population with atypical pathogens. Of 101 intent-to-treat patients with atypical pathogens, a total of 39 moxifloxacin-treated and 47 comparator-treated subjects were microbiologically valid and included in the analysis. Clinical and bacteriological success rates were 95% for the moxifloxacin-treated and 94% for the comparator-treated subjects at the test-of-cure visit. The results indicate IV/PO moxifloxacin (400 mg q.i.d.) is an effective monotherapy for patients with CAP due to atypical pathogens.

Sequential IV/PO moxifloxacin treatment of patients with severe community-acquired pneumonia.

BACKGROUND: IV/PO moxifloxacin was evaluated in the treatment of hospitalized patients with severe community-acquired pneumonia (CAP). METHODS: Data were pooled from two prospective, randomized studies. In the multinational study, patients received 7-14 days IV/PO moxifloxacin 400 mg QD or IV/ PO amoxicillin clavulanate 1200/625 mg TID +/- IV/PO clarithromycin 500 mg BID. In the North American study, patients received 7-14 days IV/PO moxifloxacin 400 mg QD, IV/ PO alatrofloxacin/trovafloxacin 200 mg QD, or IV/PO levofloxacin 500 mg QD. The primary endpoint was clinical success at the test-to-cure visit. Severe CAP was defined according to the 1993 ATS criteria. RESULTS: In the clinically valid population, clinical success rates were 88% (167/190) for moxifloxacin- and 83% (155/186) for comparator-treated patients (95% CI = -1.9%, 12.2%). Corresponding clinical success rates for the microbiologically valid population were 87% (59/68) and 84% (54/64), respectively (95% CI = 8.6%, 15.0%). A switch from IV to PO therapy was made by day 5 of therapy for 73% of moxifloxacin- vs. 60% of comparator-treated patients (P < 0.01). Clinical success rates were similar in a retrospective analysis using the revised 2001 ATS definition of severe CAP. Mortality rates were 6% (15/241) and 10% (24/238) in the moxifloxacin and comparator treatment groups, respectively. The incidence of drug-related adverse events was similar in both treatment groups. CONCLUSION: Sequential IV/PO moxifloxacin 400 mg QD is as safe and effective as other fluoroquinolones and a beta-lactam/macrolide combination for treating hospitalized patients with severe CAP.

Efficacy and safety of ciprofloxacin oral suspension versus trimethoprim-sulfamethoxazole oral suspension for treatment of older women with acute urinary tract infection.

OBJECTIVES: To compare the efficacy and safety of ciprofloxacin (CIP) oral suspension to trimethoprim/sulfamethoxazole (TMP/SMX) oral suspension among older women with acute urinary tract infections (UTIs). DESIGN: Prospective, randomized, open-label, multicenter study of older women (age 65 and older). SETTING: Community and nursing home. PARTICIPANTS: A total of 261 older women were evaluable for safety. Of these, 172 (86 community, 86 nursing home) were evaluable for clinical and bacteriological efficacy. INTERVENTION: Patients were randomized to a 10-day regimen of either CIP (250 mg/5 mL twice daily) or TMP/SMX (160/800 mg/20 mL twice daily). MEASUREMENTS: Clinical response 4 to 10 days posttherapy. RESULTS: For the efficacy-valid population, posttherapy clinical resolution was statistically superior following CIP (97%) versus TMP/SMX (85%) (95% CI=2.0-21.3; P= .009). Eradication of pretreatment bacterial isolates posttherapy was also higher following CIP (95%) versus TMP/SMX (84%) (95% CI=2.7-21.3; P= .019). For the intent-to-treat population, posttherapy clinical resolution was significantly higher in the CIP group (96%) than in the TMP/SMX group (87%) (95% CI=0.2-16.7; P= .025). Safety was assessed in the intent-to-treat population and the incidence of drug-related adverse events were significantly lower following CIP (17%) than following TMP/SMX (27%) (P= .047). Premature discontinuation due to these events was also less prevalent with CIP than with TMP/SMX (2% vs 11%, respectively) (P= .004). CONCLUSION: CIP suspension showed higher clinical success and bacteriological eradication rates than did TMP/SMX for both community-based and nursing home-residing older women with acute UTIs. Furthermore, CIP suspension was associated with significantly lower rates of adverse events and premature discontinuations compared with TMP/SMX suspension.

Retrospective analysis of the safety profile of oral and intravenous ciprofloxacin in a geriatric population.

BACKGROUND: Ciprofloxacin is a broad-spectrum fluoroquinolone antibiotic used in the treatment of a wide range of mild to moderate gram-positive and gram-negative infections. Although extensive information is available on the safety profile of ciprofloxacin in adults, few published data exist regarding the tolerability and toxicity of this drug in patients aged > or = 65 years. OBJECTIVES: The objectives of this retrospective analysis were to compare the safety profile of ciprofloxacin in patients aged > or = 65 years versus patients aged <65 years and to compare the adverse-event profile of ciprofloxacin with that of other comparator antimicrobial agents used in clinical trials. METHODS: We retrospectively reviewed 23 prospective, controlled anti-infective clinical trials in the US Bayer ciprofloxacin database that included patients aged > or = 65 years. These trials comprised the submission file of the original and supplemental New Drug Application for ciprofloxacin. The incidence of treatment-emergent and drug-related adverse events was assessed. RESULTS: Of the 6863 patients in these 23 clinical trials, 3579 received ciprofloxacin therapy and 3284 received comparator antimicrobial agents. Of the ciprofloxacin-treated patients, 898 (25.1%) were aged > or = 65 years; 887 (27.0%) of the patients who received comparator antimicrobial agents were aged > or = 65 years. Among ciprofloxacin-treated patients, drug-related adverse events were reported more often in those aged <65 years (24.0%) compared with those aged > or = 65 years (17.9%). The incidence of drug-related adverse events in the comparator group was also higher in those aged <65 years (25.1%) than in those aged > or = 65 years (16.8%). Premature discontinuation due to any adverse event was reported in 3.9% (105 of 2681) and 3.7% (33 of 898) of ciprofloxacin-treated patients aged <65 years and > or = 65 years, respectively. Corresponding rates for the comparator antimicrobial group were 3.9% (93 of 2397) and 3.8% (34 of 887), respectively, for patients aged <65 years and > or = 65 years. The most common drug-related adverse events reported for ciprofloxacin-treated patients aged <65 years and > or = 65 years were digestive system-related (18.1% and 11.4%, respectively) and central nervous system-related events (6.6% and 4.9%, respectively). CONCLUSIONS: This retrospective analysis suggests that there is no clinically important difference in the safety profile of ciprofloxacin in patients aged > or = 65 years versus patients aged <65 years.

Comparison of intravenous/oral ciprofloxacin plus metronidazole versus piperacillin/tazobactam in the treatment of complicated intraabdominal infections.

OBJECTIVE: To compare the safety and efficacy of intravenous (IV) ciprofloxacin plus IV metronidazole (CIP+MET) with that of IV piperacillin/tazobactam (PIP/TAZO) in adults with complicated intraabdominal infections, and to compare the efficacy of sequential IV-to-oral CIP+MET therapy with that of the IV CIP-only regimen. SUMMARY BACKGROUND DATA: Treatment of intraabdominal infections remains a challenge, mainly because of their polymicrobial etiology and attendant death and complications. Antimicrobial regimens using sequential IV-to-oral therapy may reduce the length of hospital stay. METHODS: In this multicenter, randomized, double-blind trial involving 459 patients, clinically improved IV-treated patients were switched to oral therapy after 48 hours. Overall clinical response was the primary efficacy measurement. RESULTS: A total of 282 patients (151 CIP+MET, 131 PIP/TAZO) were valid for efficacy. Of these patients, 64% CIP+MET and 57% PIP/TAZO patients were considered candidates for oral therapy. Patients had a mean APACHE II score of 9.6. The most common diagnoses were appendicitis (33%), other intraabdominal infection (29%), and abscess (25%). Overall clinical resolution rates were statistically superior for CIP+MET (74%) compared with PIP/TAZO (63%). Corresponding rates in the subgroup suitable for oral therapy were 85% for CIP+MET and 70% for PIP/TAZO. Postsurgical wound infection rates were significantly lower in CIP+MET (11%) versus PIP/TAZO patients (19%). Mean length of stay was 14 days for CIP+MET and 17 days for PIP/TAZO patients. CONCLUSION: CIP+MET, initially administered IV and followed by CIP+MET oral therapy, was clinically more effective than IV PIP/TAZO for the treatment of patients with complicated intraabdominal infections.

Efficacy and safety of ten day moxifloxacin 400 mg once daily in the treatment of patients with community-acquired pneumonia. Community Acquired Pneumonia Study Group.

Community-acquired pneumonia (CAP) remains a common and serious illness with approximately 2-4 million cases reported annually. Management of CAP is therapeutically challenging due to the increasing prevalence of penicillin- and macrolide-resistant pneumococci and beta-lactamase producing Haemophilus influenzae, as well as the increased recognition of 'atypical' pathogens, such as Chlamydia pneumoniae and Mycoplasma pneumoniae, and the frequent need for empiric therapy. We aimed to evaluate the safety and efficacy of moxifloxacin in the treatment of patients with CAP. To do this we carried out a prospective, uncontrolled, non-blind, Phase III clinical trial, in 27 U.S. centers. Patients included in the study were over 18 years of age with signs and symptoms of CAP confirmed by evidence of a new or progressive infiltrate on chest radiograph. The intervention used was moxifloxacin 400 mg PO once daily for 10 days. Sputum samples were collected pretherapy for Gram stain and culture for typical organisms. Culture and serological testing for Chlamydia pneumoniae and Mycoplasma pneumoniae was also performed. Susceptibility to moxifloxacin was determined by disk diffusion and MIC. Clinical and bacteriological responses were determined at the end of therapy (0-6 days post-therapy), follow-up (14-35 days post-therapy) and overall (end of therapy plus follow-up). Analyses were performed on both valid for efficacy and intent-to-treat populations. The primary efficacy variable was overall clinical resolution. Of 254 patients enrolled in the Study, 196 patients were included in the efficacy analyses. The majority of patients were male (58%) and Caucasian (85%) with a mean age of 49 years (range: 18 to 85 years). Only 3% of patients were hospitalized pretherapy. The most common pretherapy organisms identified, by culture or serology, in the valid for efficacy population (i.e. 147 organisms among 116 patients), were: Chlamydia pneumoniae (n=63; 54%), Mycoplasma pneumoniae (n=29; 25%), Streptococcus pneumoniae (n=14; 12%) and Haemophilus influenzae (n=13; 10%). End of therapy, follow-up and overall clinical resolution rates for the valid for efficacy population were 94%, 93% and 93%, respectively. The 95% CI for the overall clinical resolution rate was 88.1%, 95.9%. The overall bacteriological response for patients diagnosed by culture or serological criteria, was 91% (95% CI=84%, 96%). For patients who only met serological criteria for infection, the overall bacteriological response was 94% (60/64). Bacterial response rates for the four most commonly isolated pathogens were: 89% (56/63) for C. pneumoniae, 93% (27/29) for M. pneumoniae, 93% (13/14) for S. pneumoniae and 85% (11/13) for H. influenzae. Drug-related adverse events were reported in 33% (85/254) of moxifloxacin-treated patients. Nausea (9%), diarrhea (6%) and dizziness (4%) were the most commonly reported adverse events. Atypical organisms were isolated in high frequency among patients with CAP. Moxifloxacin 400 mg once daily for 10 days was effective and well-tolerated in the treatment of these adult patients with CAP. Moxifloxacin offers an effective treatment alternative for CAP due to both typical and atypical bacterial pathogens.

Short-course moxifloxacin therapy for treatment of acute bacterial exacerbations of chronic bronchitis. The Bronchitis Study Group.

Chronic bronchitis is common among adults and infectious exacerbations contribute considerably to morbidity and mortality. We aimed to compare the safety and efficacy of moxifloxacin to clarithromycin for the treatment of patients with acute bacterial exacerbations of chronic bronchitis (ABECB) using a prospective, randomized, double-blind, parallel group trial. Between November 21, 1996 and April 7, 1998, 936 patients with acute exacerbations of chronic bronchitis (AECB) were enrolled at 56 centers across the United States of which 491 (52%) had ABECB (i.e. pretherapy pathogen). Patients were randomized to either oral moxifloxacin 400 mg administer once daily, for either 5 or 10 days, or clarithromycin 500 mg bid for 10 days. For the purpose of study blinding, the patients taking moxifloxacin received placebo to maintain uniform dosing. The main outcome measures were bacteriological response at the end of therapy (post-therapy days 0-6) and follow-up (7-17 days post-therapy) visits, as well as overall clinical response, clinical response at the end of therapy and clinical response at follow-up. Two patient populations were analyzed: efficacy-valid (i.e., those with a pretherapy pathogen) and intent-to-treat (i.e., all subjects that took drug). In 420 efficacy valid patients with a pretherapy organism, overall clinical resolution was 89% for 5 days moxifloxacin vs. 91% for 10 day moxifloxacin vs. 91% for 10 day clarithromycin. Bacteriological eradication rates at the end of therapy were 94% and 95% for 5-day moxifloxacin and 10-day moxifloxacin, respectively, and 91% for the clarithromycin group. Eradication rates at follow-up were 89% and 91% for 5-day moxifloxacin and 10-day moxifloxacin respectively, and 85% for the clarithromycin group. Among 926 intent-to-treat patients (312 5-day moxifloxacin, 302 10-day moxifloxacin and 312 clarithromycin), drug-related events were reported for 26%, 30% and 35%, respectively. Moxifloxacin 400 mg once daily, as a 5 or 10 day regimen, was found to be clinically and bacteriologically equivalent to 10 day clarithromycin for the treatment of ABECB. Given its favorable safety and tolerability profile, moxifloxacin administered once daily for 5 days may be as effective and a more convenient treatment than a standard course of clarithromycin for patients with ABECB.

Moxifloxacin versus cephalexin in the treatment of uncomplicated skin infections.

The efficacy and safety of oral moxifloxacin (400 mg once daily, 7 days) versus cephalexin (500 mg three times daily, 7 days) were compared in a prospective, multicentre, randomised, double-blind trial in 401 adults with uncomplicated skin infections. Clinical outcome was evaluated in 351 patients. Moxifloxacin proved to be as effective as cephalexin both clinically (90% versus 91%, respectively) and bacteriologically in eradicating the most frequently isolated pathogen Staphylococcus aureus (92% and 93%, respectively). Moxifloxacin was more effective than cephalexin in eliminating Streptococcus spp. (90% and 82%, respectively). Drug-related adverse events were comparable in both treatment groups with the most frequently reported being nausea in the moxifloxacin-treated patients and headache in the cephalexin-treated patients. Medication was discontinued due to unwanted reactions in 3% of the moxifloxacin- and 4% of the cephalexin-treated patients. Moxifloxacin, 400 mg once daily for 7 days, is as safe and effective as cephalexin 500 mg three times daily for 7 days in the treatment of uncomplicated skin infections.

Comparison of moxifloxacin and cefuroxime axetil in the treatment of acute maxillary sinusitis. Sinusitis Infection Study Group.

The aim of this prospective, multicenter, randomized, double-masked clinical trial was to compare the efficacy and safety of moxifloxacin with those of cefuroxime axetil for the treatment of community-acquired acute sinusitis. Five hundred forty-two adult patients with symptoms and radiographic evidence of acute maxillary sinusitis received a 10-day oral regimen of either moxifloxacin (400 mg once daily) or cefuroxime axetil (250 mg twice daily). Acute signs and symptoms at presentation had lasted >7 days but <4 weeks. Clinical response at the end of therapy (7 to 14 days after treatment) was the primary efficacy variable. Four hundred fifty-seven of the patients (223 moxifloxacin, 234 cefuroxime axetil) were included in the clinical efficacy analysis. Moxifloxacin was found to be similar in effectiveness to cefuroxime axetil at the end-of-therapy visit (90% vs. 89%, respectively; 95% confidence interval, -5.1% to 6.2%). Clinical relapse at the follow-up visit was reported for only 8 patients (3 moxifloxacin, 5 cefuroxime axetil). No clinically significant differences were observed with respect to the number of patients experiencing a successful clinical response based on demographic or infection characteristics. Five of the 542 enrolled patients were lost to follow-up. Of the 537 patients in the intent-to-treat population, drug-related adverse events were reported in 37% of moxifloxacin-treated patients and in 26% of cefuroxime axetil-treated patients (P = 0.006). Adverse-event profiles were comparable in the 2 treatment groups, with the exception of nausea, which was reported by 11% of moxifloxacin-treated patients compared with 4% of cef uroxime axetil-treated patients (P = 0.003). In this study, moxifloxacin was as effective as cefuroxime axetil in the treatment of community-acquired acute sinusitis.

Cystic fibrosis clinical score: a new scoring system to evaluate acute pulmonary exacerbation.

Although pulmonary function tests are used to evaluate acute changes in obstructive airway disease in patients with cystic fibrosis (CF), these tests are relatively difficult to perform in young children or severely ill patients and may be costly. Other standard tests (eg, the Shwachman-Kulczycki and National Institutes of Health [NIH] scoring systems) evaluate disease severity and predict prognosis but do not measure day-to-day changes in clinical status. They thus provide little information for assessing the start of acute pulmonary exacerbation. Alternative scoring systems are needed to better identify the start of pulmonary exacerbation, to predict worsening or improvement of respiratory function after intervention, and to distinguish the scores from illness severity scores. This study was undertaken to compare a new 10-component, 50-point-maximum, acute clinical scoring system with forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) variables in children with CF who were experiencing an acute pulmonary exacerbation before antimicrobial therapy was initiated and until the end of therapy. One hundred thirty children aged 5 to 17 years (median age, 11 years) had a median NIH score of approximately 64 (range, 39 to 85) at admission. The cystic fibrosis clinical score (CFCS) at admission was found to correlate highly with the modified NIH score at study entry (r = -.68, P = 0.0001 ). The total CFCS at entry was correlated inversely with both FEV1 (r = -.57, P = 0.0001) and FVC (r = -.55, P = 0.0001) measurements; crackles, dyspnea, sputum production, and respiratory rate were the 4 components most highly associated with either pulmonary function variable. The change in total CFCS from start to end of antimicrobial therapy also correlated with changes in FEV1 (r = -.31, P = 0.0016) and change in FVC (r = -.47, P = 0.0001). Clinical improvement was observed in all patients at the end of therapy, and only 1 patient had an increase in total CFCS. Patients who experienced clinical relapse had a mean increase of 8.5 points in the CFCS from end of therapy to 2- to 4-week follow-up, indicating worsening signs and symptoms of acute exacerbation. These data suggest that the CFCS is a predictive and optional surrogate of pulmonary function in assessing the health of patients with CF. Following further validation, this scoring system could be used to evaluate health status in the outpatient setting, the need for hospitalization, and subsequent improvement during an acute pulmonary exacerbation, as well as to compare the efficacy of therapeutic regimens.

Demographic, clinical, and treatment parameters influencing the outcome of acute cystitis.

A meta-analysis of six double-blinded clinical trials was undertaken to identify risk factors associated with bacteriologic outcome in 3,108 women with acute cystitis. Eleven antibiotic regimens were used, including ciprofloxacin, ofloxacin, norfloxacin, trimethoprim-sulfamethoxazole, and nitrofurantoin. Entry criteria for all studies were identical. Among 2,409 patients who were defined to be valid for efficacy analysis, pathogens included Escherichia coli (78.6%), Staphylococcus saprophyticus (4.4%), Klebsiella pneumoniae (4.3%), Proteus mirabilis (3.7%), and "other" (9%). Causative bacteria were eradicated at the end of treatment in 93% of patients. The following parameters were associated with successful bacteriologic outcome: not using a diaphragm (P = .0041), treatment for > or = 3 days (P = .0043), pathogen not "other" (P = .0043), symptom duration of < 2 days (P = .0096), and African American race (P = .0147). K. pneumoniae (P = .0496) and "other" pathogens (P = .0018) were associated with increased probability of bacteriologic treatment failure. The presence of pyuria (> or = 10 WBCs per high-power field) did not correlate with outcome and was inversely correlated with the finding of > or = 10(5) bacterial colony-forming units per mL of urine (P < .001). This large database identifies new parameters associated with treatment outcomes of acute cystitis and calls into question current clinical trial guidelines.

Intravenous and oral mono- or combination-therapy in the treatment of severe infections: ciprofloxacin versus standard antibiotic therapy. Ciprofloxacin Study Group.

Five hundred and forty patients with severe infection were enrolled in a multicentre, prospective, randomized, non-blinded study to compare the efficacy and safety of i.v. ciprofloxacin with i.v. standard therapy. Five hundred and thirty-one patients received at least one dose of study drug for pneumonia (310), septicaemia (112) or skin and skin structure infection (109). Intravenous ciprofloxacin (400 mg, every 8 h) or i.v. ciprofloxacin (400 mg, every 8 h) plus a beta-lactam were compared with a standard monotherapy (beta-lactam) or combination (aminoglycoside plus a beta-lactam) therapy. Patients were treated parenterally for a minimum of 2 or 3 days, then at the discretion of the investigator could be switched to oral therapy (ciprofloxacin 750 mg, every 12 h or a standard oral therapy). Patients were randomized in the ratio of 2:1 for the ciprofloxacin and standard therapy treatment groups and stratified to monotherapy if the APACHE II score was < or = 20 or to combination therapy if the APACHE II score was 21-29. Three hundred and ninety-five (74%) patients were valid for the efficacy analysis: these comprised 242 pneumonia (167 ciprofloxacin and 75 standard therapy), 70 septicaemia (47 ciprofloxacin and 23 standard therapy), and 83 skin infections (56 ciprofloxacin and 27 standard). The primary efficacy variable was clinical response and the secondary efficacy assessment was bacteriological response at the end of therapy (2 or 3 days after treatment). The mean duration of therapy for patients receiving only i.v. monotherapy or combination therapy was shorter (9-10 days) than for patients receiving sequential i.v./p.o. therapy (14-17 days). At the end of therapy, overall clinical resolution/improvement (success) for monotherapy was 138/166 (83%) for the ciprofloxacin group, compared with 74/87 (85%) for standard-treated patients (95% CI = -11.5% to 7.6%), and for combination therapy the response was 43/51 (84%) for the ciprofloxacin group and 14/20 (70%) for standard-treated patients (95% CI = -6.3% to 34.9%). For pneumonia, the most frequent infection treated, clinical success rates following monotherapy were 85% for ciprofloxacin and 83% for standard-treated patients and 83% for ciprofloxacin compared with 69% for standard-treated patients in the combination therapy group. Bacteriological eradication/presumed eradication following monotherapy was 85/102 (83%) for ciprofloxacin and 31/46 (67%) for standard-treated patients (95% CI = 1.6% to 30.3%), and that for combination therapy was 29/36 (81%) for ciprofloxacin and 7/10 (70%) for standard-treated patients (95% CI = -18.3% to 39.5%). Drug-related adverse events, primarily diarrhoea and nausea, were reported in 22% of ciprofloxacin-treated patients and 20% of standard-treated patients. In summary, ciprofloxacin administered alone or in combination was found to be effective in treating a wide range of severe infections.

Safety of long-term therapy with ciprofloxacin: data analysis of controlled clinical trials and review.

We reviewed the literature and the manufacturer's U.S. clinical data pool for safety data on long-term administration of ciprofloxacin (Bayer, West Haven, CT). Only controlled clinical trials including patients treated for >30 days were selected. We identified 636 patients by literature search and 413 patients in the Bayer U.S. database who fulfilled our search criteria; the average treatment duration for these patients was 130 and 80 days, respectively. Main indications for long-term therapy were osteomyelitis, skin and soft-tissue infection, prophylaxis for urinary tract infection, mycobacterial infections, and inflammatory bowel disease. Adverse events, premature discontinuation of therapy, and deaths occurred at a similar frequency in both treatment arms. Most adverse events occurred early during therapy with little increase in frequency over time. As with short-term therapy, gastrointestinal events were more frequent than central nervous system or skin reactions, but pseudomembranous colitis was not observed. No previously unknown adverse events were noted. We conclude that ciprofloxacin is tolerated as well as other antibiotics when extended courses of therapy are required.

Efficacy and tolerability of twice-daily ciprofloxacin 750 mg in the treatment of patients with acute exacerbations of chronic bronchitis and pneumonia.

In a review of the US Bayer ciprofloxacin (CIP) database, an analysis was undertaken to summarize the effectiveness and tolerability of CIP 750 mg BID in the treatment of patients with acute exacerbations of chronic bronchitis (AECB) and pneumonia. In five controlled studies, comparator (COMP) agents included ampicillin, intravenous cefuroxime/cefaclor, and other unspecified agents. Primary efficacy end points were clinical success (resolution plus improvement) and bacteriologic eradication at the end of therapy. The incidence of adverse events for CIP 750 mg BID was compared with that for COMP and with that in the CIP 500-mg-BID AECB and pneumonia clinical trials database. In five uncontrolled studies, 443 patients received CIP 750 mg BID; in 5 controlled trials comprising 344 patients, 169 received CIP 750 mg BID and 175 received COMP. Clinical success for CIP was 93% (368/396) and 99% (160/162), respectively, in the uncontrolled and controlled studies versus 98% (156/160) for COMP agents. Corresponding bacteriologic eradication rates for CIP 750-mg-BID-treated patients were 77% (273/356) and 95% (122/128), respectively, and 77% (96/125) for COMP agents. Overall bacteriologic eradication by organism for CIP 750 mg BID included Streptococcus pneumoniae 96% (51/53), Haemophilus influenzae 98% (92/94), Haemophilus parainfluenzae 100% (56/56), Moraxella catarrhalis 100% (14/14; 13 of 14 organisms were isolated in patients with AECB), and Pseudomonas aeruginosa 66% (135/204). Drug-related adverse events were reported in 113 (26%) CIP 750-mg-BID-treated patients in uncontrolled trials and in 62 (37%) CIP 750-mg-BID- and 61 (35%) COMP-treated patients in controlled trials. In the combined data from the CIP 750-mg-BID uncontrolled and controlled trials, adverse events occurred with similar frequency compared with COMP except for nausea (CIP 10%, COMP 7%) and diarrhea (CIP 3%, COMP 13%). In conclusion, CIP 750 mg BID provided excellent clinical success rates in the treatment of patients with AECB and pneumonia. CIP 750 mg BID was well tolerated compared with the COMP agents administered.

Sequential ciprofloxacin therapy in pediatric cystic fibrosis: comparative study vs. ceftazidime/tobramycin in the treatment of acute pulmonary exacerbations. The Cystic Fibrosis Study Group.

BACKGROUND: Cystic fibrosis patients have chronic bacterial infections of the respiratory tract, most commonly Pseudomonas aeruginosa. Although controversial, administration of antibiotic therapy during acute pulmonary exacerbations is standard practice. Fluoroquinolones are currently not indicated for use in young children because of the observation of arthropathy and damage to growing cartilage in beagle puppies. Because of its activity against P. aeruginosa and excellent oral bioavailability, ciprofloxacin offers a unique therapeutic alternative for this patient population. OBJECTIVE: This prospective, randomized, double blind study compared the efficacy and safety of sequential intravenous/oral ciprofloxacin vs. ceftazidime/tobramycin in hospitalized pediatric cystic fibrosis patients with an acute pulmonary exacerbation associated with P. aeruginosa infection. METHODS: One hundred thirty patients (ages 5 to 17 years) were randomized to receive either i.v. ciprofloxacin 10 mg/kg every 8 h for 7 days followed by oral ciprofloxacin 20 mg/kg every 12 h for a minimum of 3 days or i.v. ceftazidime 50 mg/kg every 8 h plus i.v. tobramycin 3 mg/kg every 8 h for a minimum of 10 days. Clinical, bacteriologic and safety responses were assessed throughout the study. RESULTS: All 84 patients (median age, 11 years; range, 5 to 17 years) valid for efficacy in both treatment groups demonstrated clinical improvement. Five patients experienced clinical relapses (3 ciprofloxacin, 2 ceftazidime/tobramycin) by the 2- to 4-week follow-up. Intent-to-treat analysis demonstrated similar clinical findings between the two treatment groups at both the end of therapy and follow-up. Clinical improvement correlated with improvement in pulmonary function studies and the acute clinical scoring system but not with bacteriologic eradication of Pseudomonas. DNA profiles demonstrated that irrespective of colony morphology, usually one clonal strain was associated with each patient's pulmonary exacerbation. Treatment-associated musculoskeletal events occurred with equal frequency (22% vs. 21%) in both study drug groups (n = 129), and arthralgias were within the range of rates for cystic fibrosis arthropathy. None of these events required study drug discontinuation. CONCLUSION: Sequential i.v./oral ciprofloxacin monotherapy offers a safe and efficacious alternative to standard parenteral therapy for acute pulmonary exacerbations in pediatric cystic fibrosis patients.

Efficacy of ciprofloxacin and clarithromycin in acute bacterial exacerbations of complicated chronic bronchitis: interim analysis. Bronchitis Study Group.

In a multicenter, community-based study involving more than 300 primary care physicians in the United States, the efficacy and safety of ciprofloxacin and clarithromycin were compared in the treatment of patients with complicated or severe acute bacterial exacerbations of chronic bronchitis (i.e., those who had failed previous antibiotic treatment within the prior 2 to 4 weeks; those with susceptibility data suggestive of a resistant pathogen; those having three or more acute exacerbations of chronic bronchitis [AECB] within the past year; and those having three or more comorbid conditions). Patients were randomized to either ciprofloxacin (CIP) 750 mg BID or clarithromycin (CLR) 500 mg BID, both administered for 10 days; all patients were treated on an outpatient basis. Clinical response at the end of therapy was the primary efficacy variable. An interim analysis was performed on the results from 743 patients (369 CIP, 374 CLR) with clinical and bacteriologic evidence of a bronchopulmonary infection who had completed an ongoing study as of the end of May 1997. Three hundred nine pathogens were isolated before therapy, including Haemophilus spp (75 isolates), Moraxella catarrhalis (67 isolates), Staphylococcus aureus (55 isolates), and Streptococcus pneumoniae (23 isolates). Seven hundred eighteen patients (97%) were included in the efficacy-valid population. Clinical success at the end of therapy was observed in 90% (272 of 302) and 88% (274 of 313) of efficacy-valid patients treated with CIP and CLR, respectively (95% confidence interval [CI] = -2.4 to 7.6). Corresponding rates for the intent-to-treat population were also 90% (283 of 314) and 88% (281 of 321), respectively (95% CI = -2.3 to 7.5). The bacteriologic response for efficacy-valid patients at the end of therapy was 98% (119 of 122) for CIP-treated and 93% (103 of 111) for CLR-treated patients (95% CI = -0.8 to 10.2). The eradication rates for the three most commonly isolated gram-negative pathogens were 100% for CIP-treated and 95% for CLR-treated patients and 96% each for the two most commonly isolated gram-positive organisms. Superinfections due to respiratory tract pathogens were more common in the CLR group (10 organisms) than in the CIP group (4 organisms). Seventy-four (20%) CIP-treated and 62 (17%) CLR-treated patients reported 118 and 103 respective study-emergent adverse events. Headache, abdominal pain, diarrhea, nausea, and vomiting in CIP-treated patients and diarrhea, nausea, vomiting, and taste perversion in CLR-treated patients were the most commonly reported adverse events. Treatment of patients with complicated or severe AECB with CIP 750 mg BID was associated with rates of clinical success and bacteriologic eradication similar to those with CLR.