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

Abstract

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.

Broad‐Spectrum Antimicrobials and the Treatment of Serious Bacterial Infections: Getting It Right Up Front

“…Monotherapy with cefditoren pivoxil achieved clinical cure rates, microbiological cure rates, and overall eradication rates comparable to those associated with amoxicillin/clavulanate [72]. Ciprofloxacin, as monotherapy or in combination with a b-lactam, showed efficacy similar to that of standard monotherapy with a b-lactam or standard combination therapy with an aminoglycoside plus a b-lactam [73].…”

Quinolones for Treatment of Nosocomial Pneumonia: A Meta-Analysis

“…Reasons for exclusion included the following: (1) not randomized ( ), (2) small sample size ( ), (3) used quin-n p 25 n p 5 olones not commercially available ( ), (4) community-n p 4 acquired pneumonia study rather than a trial of NP ( ), n p 3 (5) not comparator controlled ( ), and (6) lost 120% of n p 3 cohort to follow-up ( ). n p 1 The 5 studies included in the final evaluation comprised a total of 1186 patients [17][18][19][20][21]. The median quality score (as defined by Jadad et al [16]) was 6 (range, 5-7).…”

“…Only the investigation conducted by Fink et al [17] was double blind; the remainder were open-label studies. Four of the 5 trials used ciprofloxacin [17][18][19][20], but that by West et al focused on levofloxacin [21]. All the trials of ciprofloxacin used doses Because "positive" trials (i.e., those that detect a difference associated with an intervention) are more likely to be published, it is important, when performing a meta-analysis, to search for "negative" trials (i.e., those that fail to note a difference between control and intervention groups).…”

“…of 300-400 mg iv q8h [17][18][19][20]. Three investigations compared quinolones with carbepenems (imipenem-cilistatin), and 1 used ceftazadime as the comparator [17,20,21].…”

Antimicrobial therapy for patients with severe sepsis and septic shock: An evidence-based review

“…More recently, five studies, of which four enrolled only patients with severe community-acquired or nosocomial pneumonias, showed that fluoroquinolones (ciprofloxacin, four studies; levofloxacin, one study) were as efficacious as ␤-lactam antibiotics (imipenem in four studies; various ␤-lactams with or without an aminoglycoside in one study) for the treatment of patients with severe sepsis caused predominantly by Gramnegative bacteria (Table 2) (56,105,106,109,110). Of note, a large number of patients (ranging between 250 and 400) were randomized in three of the four pneumonia studies.…”