Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. The Severe Pneumonia Study Group

Abstract

Intravenously administered ciprofloxacin was compared with imipenem for the treatment of severe pneumonia. In this prospective, randomized, double-blind, multicenter trial, which included an intent-to-treat analysis, a total of 405 patients with severe pneumonia were enrolled. The mean APACHE II score was 17.6, 79%o of the patients required mechanical ventilation, and 78% had nosocomial pneumonia. A subgroup of 205 patients (98 ciprofloxacin-treated patients and 107 imipenem-treated patients) were evaluable for the major efficacy endpoints. Patients were randomized to receive intravenous treatment with either ciprofloxacin (400 mg every 8 h) or imipenem (1,000 mg every 8 h), and doses were adjusted for renal function. The primary and secondary efficacy endpoints were bacteriological and clinical responses at 3 to 7 days after completion of therapy. Ciprofloxacin-treated patients had a higher bacteriological eradication rate than did imipenem-treated patients (69 versus 59%o; 95% confidence interval of -0.6%, 26.2%; P = 0.069) and also a significantly higher clinical response rate (69 versus 56%; 95% confidence interval of 3.5%, 28.5%; P = 0.021). The greatest difference between ciprofloxacin and imipenem was in eradication of members of the family Enterobateriaceae (93 versus 65%; P = 0.009). Stepwise logistic regression analysis demonstrated the following factors to be associated with bacteriological eradication: absence of Pseudomonas aeruginosa (P < 0.01), higher weight (P < 0.01), a low APACHE IH score (P = 0.03), and treatment with ciprofloxacin (P = 0.04). When P. aeruginosa was recovered from initial respiratory tract cultures, failure to achieve bacteriological eradication and development of resistance during therapy were common in both treatment groups (67 and 33% for ciprofloxacin and 59 and 53% for imipenem, respectively). Seizures were observed more frequently with imipenem than with ciprofloxacin (6 versus 1%; P = 0.028). These results demonstrate that in patients with severe pneumonia, monotherapy with ciprofloxacin is at least equivalent to monotherapy with imipenem in terms of bacteriological eradication and clinical response. For both treatment groups, the presence of P. aeruginosa had a negative impact on treatment success. Seizures were more common with imipenem than with ciprofloxacin. Monotherapy for severe pneumonia is a safe and elfective initial strategy but may need to be modified if P. aeruginosa is suspected or recovered from patients.Despite improvements in antimicrobial chemotherapy and supportive care, bacterial pneumonia, whether nosocomial or community acquired, remains an infection with substantial mortality. Nosocomial pneumonia accounts for about 15% of

Carbapenems for the treatment of immunocompetent adult patients with nosocomial pneumonia

“…From these, 51 RCTs did not meet the inclusion criteria of the current meta-analysis for the reasons detailed in figure 1. Thus, 12 RCTs [64][65][66][67][68][69][70][71][72][73][74][75] were included in the current meta-analysis. Table 1 lists the characteristics of the 12 RCTs [64][65][66][67][68][69][70][71][72][73][74][75] included in the meta-analysis.…”

“…The mean (range) quality score of the included RCTs was 2.42 (1-5), which was considered good. The quality of five RCTs [64][65][66][67]74] was high (o3), while the quality of seven [68][69][70][71][72][73]75] was low (f2). The proportion of patients under mechanical ventilation was 100% in three trials [67,68,71], .70% in five trials [64-66, 72, 74] and 50% in two RCTs [69,75], while the remaining RCTs [70,73] did not provide relevant data.…”

Cefepime-ResistantPseudomonas aeruginosa

“…Complicating the empiric selection of adequate therapy is the increasing prevalence of antimicrobial drug resistance among P. aeruginosa (8)(9)(10). Even in initially susceptible strains, resistance can rapidly develop during treatment (11)(12)(13).…”

Combinationversusmonotherapy for nosocomial pneumonia

“…It was concluded that combination therapy using a fourth-generation cephalosporin with either an aminoglycoside or a fluoroquinolone was not associated with a clinical or biological benefit when compared with cephalosporin monotherapy for common, susceptible pathogens causing VAP [5]. Of the many comparative studies for the treatment of VAP, six are summarised in table 2 [6][7][8][9][10][11]. Perhaps the best of these studies compared imipenem alone with the combination of imipenem and netilmicin [8].…”