cilastatin--imipenem-drug-combination and Cross-Infection

Although early use of broad-spectrum antimicrobials in critically ill patients may increase antimicrobial adequacy, uncontrolled use of these agents may select for more-resistant organisms. This study investigated the effects of early use of broad-spectrum antimicrobials in critically ill patients with hospital-acquired pneumonia.. We compared the early use of broad-spectrum antimicrobials plus subsequent de-escalation (DE) with conventional antimicrobial treatment (non-de-escalation, NDE) in critically ill patients with hospital-acquired pneumonia (HAP). This open-label, randomized clinical trial was performed in patients in a tertiary-care center medical intensive care unit (MICU) in Korea. Patients (n=54) randomized to the DE group received initial imipenem/cilastatin plus vancomycin with subsequent de-escalation according to culture results, whereas patients randomized to the NDE group (n=55) received noncarbapenem, nonvancomycin empiric antimicrobials.. Between November 2004 and October 2006, 109 MICU patients with HAP were enrolled. Initial antimicrobial adequacy was significantly higher in the DE than in the NDE group for Gram-positive organisms (100% versus 14.3%; P<0.001), but not for Gram-negative organisms (64.3% versus 85.7%; P=0.190). Mean intensive care unit (ICU) stay, and 14-day, 28-day, and overall mortality rates did not differ in the two groups. Among culture-positive patients, mortality from methicillin-resistant Staphylococcus aureus (MRSA) pneumonia was higher in the DE group, even after early administration of vancomycin. Multidrug-resistant organisms, especially MRSA, were more likely to emerge in the DE group (adjusted hazard ratio for emergence of MRSA, 3.84; 95% confidence interval, 1.06 to 13.91).. The therapeutic advantage of early administration of broad-spectrum antimicrobials, especially with vancomycin, was not evident in this study.

Topics: Aged; Anti-Infective Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Cross Infection; Drug Combinations; Female; Hospital Mortality; Humans; Imipenem; Intensive Care Units; Male; Middle Aged; Pneumonia, Bacterial; Time Factors; Treatment Outcome; Vancomycin

To compare efficacy and safety of a tigecycline regimen with an imipenem/cilastatin regimen in hospital-acquired pneumonia patients, a phase 3, multicenter, randomized, double-blind, study evaluated 945 patients. Coprimary end points were clinical response in clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure. Cure rates were 67.9% for tigecycline and 78.2% for imipenem (CE patients) and 62.7% and 67.6% (c-mITT patients), respectively. A statistical interaction occurred between ventilator-associated pneumonia (VAP) and non-VAP subgroups, with significantly lower cure rates in tigecycline VAP patients compared to imipenem; in non-VAP patients, tigecycline was noninferior to imipenem. Overall mortality did not differ between the tigecycline (14.1%) and imipenem regimens (12.2%), although more deaths occurred in VAP patients treated with tigecycline than imipenem. Overall, the tigecycline regimen was noninferior to the imipenem/cilastatin regimen for the c-mITT but not the CE population; this difference appears to have been driven by results in VAP patients.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cross Infection; Double-Blind Method; Drug Combinations; Hospital Mortality; Humans; Imipenem; Microbial Sensitivity Tests; Minocycline; Pneumonia; Pneumonia, Ventilator-Associated; Tigecycline; Treatment Outcome

Ventilator-associated pneumonia (VAP) remains a significant challenge in critical care. We conducted a secondary analysis of a multicenter, prospective, randomized trial comparing levofloxacin (750 mg iv q24h) with imipenem-cilastatin (500-1000 mg iv q6-8h) for treatment of nosocomial pneumonia and focused on the subgroup of patients with VAP. The study cohort included 222 patients, with half (111) of the patients assigned to each treatment group. The patients in both groups were similar with respect to age, severity of illness, and duration of mechanical ventilation before the onset of VAP. Among the intention-to-treat population, clinical success was achieved in 58.6% of patients receiving levofloxacin, compared with 63.1% of patients receiving imipenem-cilastatin (P=.49; 95% confidence interval for the difference, -8.77% to 17.79%). Microbiological success and 28-day mortality rates were also comparable. Multivariate analysis demonstrated that assignment to antibiotic treatment (i.e., levofloxacin vs. imipenem-cilastatin) was not predictive of outcomes, thus suggesting that the treatment regimens were equivalent. Both levofloxacin and imipenem-cilastatin regimens were well tolerated and had similar adverse event profiles.

Topics: Anti-Bacterial Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Cohort Studies; Cross Infection; Double-Blind Method; Drug Combinations; Drug Resistance, Bacterial; Female; Humans; Imipenem; Levofloxacin; Male; Middle Aged; Multivariate Analysis; Ofloxacin; Pneumonia, Bacterial; Prospective Studies; Thienamycins; Treatment Outcome; Ventilators, Mechanical

We compared two imipenem regimens for prevention of septic complications in patients with severe acute necrotizing pancreatitis (ANP).. Prospective, randomized open clinical trial involving intensive care units of 14 Spanish Hospitals.. 92 patients with ANP.. Imipenem/cilastatin was administered at 500 mg four times daily starting at the time of diagnosis of ANP, within the first 96 h from the onset of symptoms. Patients were randomized to receive antibiotic prophylaxis either for 14 days (group 1) or at least for 14 days and as long as major systemic complications of the disease persisted (group 2).. Antibiotic was maintained in group 2 for 19.7+/-10.9 days. The incidence of infected pancreatic necrosis, pancreatic abscess, and extrapancreatic infections was 11%, 17%, and 28% in group 1 and 17.4%, 13%, and 35% in group 2 (n.s.). Pancreatic or extrapancreatic infection by Candida albicans occurred in 7% and 22% of patients. Global mortality was 18.5% (10.9% secondary to septic complications), without differences between groups. In patients with persisting systemic complications at day 14 mortality was almost always secondary to septic complications and decreased from 25% (group 1) to 8.8% (group 2) by maintaining antibiotic prophylaxis.. Compared to a 14-day imipenem prophylaxis, a longer antibiotic administration in patients with ANP is not associated with a reduction in the incidence of septic complications of the disease. However, prolonged imipenem administration in patients with persisting systemic complications tends to reduce mortality in ANP compared to a 14-days regimen.

Topics: Aged; Antibiotic Prophylaxis; APACHE; Cause of Death; Cilastatin; Cilastatin, Imipenem Drug Combination; Cross Infection; Drug Administration Schedule; Drug Combinations; Female; Hospital Mortality; Humans; Imipenem; Incidence; Infection Control; Male; Middle Aged; Pancreatitis, Acute Necrotizing; Prospective Studies; Sepsis; Severity of Illness Index; Spain; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

Nosocomial pneumonia and acute peritonitis may be caused by a wide array of pathogens, and combination therapy is often recommended. We have previously shown that imipenem-cilastatin monotherapy was as efficacious as the combination of imipenem-cilastatin plus netilmicin in these two settings. The efficacy of imipenem-cilastatin is now compared to that of piperacillin-tazobactam as monotherapy in patients with nosocomial pneumonia or acute peritonitis. Three hundred seventy one patients with nosocomial pneumonia or peritonitis were randomly assigned to receive either imipenem-cilastatin (0.5 g four times a day) or piperacillin-tazobactam (4.5 g three times a day). Three hundred thirteen were assessable (154 with nosocomial pneumonia and 159 with peritonitis). For nosocomial pneumonia, clinical-failure rates in the piperacillin-tazobactam group (13 of 75 [17%]) and in the imipenem-cilastatin group (23 of 79 [29%]) were similar (P = 0.09), as were the numbers of deaths due to infection (6 in the imipenem-cilastatin group [8%], 7 in the piperacillin-tazobactam group [9%]) (P = 0.78). For acute peritonitis, clinical success rates were comparable (piperacillin-tazobactam, 72 of 76 [95%]; imipenem-cilastatin, 77 of 83 [93%]). For infections due to Pseudomonas aeruginosa, 45 patients had nosocomial pneumonia (21 in the piperacillin-tazobactam group and 24 in the imipenem-cilastatin group) and 10 had peritonitis (5 in each group). In the patients with nosocomial pneumonia, clinical failure was less frequent in the piperacillin-tazobactam group (2 of 21 [10%]) than in the imipenem-cilastatin [corrected] group (12 of 24 [50%]) (P = 0.004). Bacterial resistance to allocated regimen was the main cause of clinical failure (1 in the piperacillin-tazobactam group and 12 in the imipenem-cilastatin group). For the patients with peritonitis, no difference in clinical outcome was observed (five of five cured in each group). The overall frequencies of adverse events related to treatment in the two groups were similar (24 in the piperacillin-tazobactam group, 22 in the imipenem-cilastatin group). Diarrhea was significantly more frequent in the piperacillin-tazobactam group (10 of 24) than in the imipenem-cilastatin group (2 of 22). This study suggests that piperacillin-tazobactam monotherapy is at least as effective and safe as imipenem-cilastatin monotherapy in the treatment of nosocomial pneumonia or peritonitis. In P. aeruginosa pneumonia, piperacillin-tazobactam achieved

Topics: Acute Disease; Adult; Aged; Cilastatin; Cilastatin, Imipenem Drug Combination; Cross Infection; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Middle Aged; Penicillanic Acid; Peritonitis; Piperacillin; Pneumonia; Prospective Studies; Pseudomonas Infections; Tazobactam

The clinical and bacteriological efficacy and the tolerability of meropenem versus imipenem/cilastatin (both 1 g t.i.d.) in severe nosocomial infections were compared in a multicentre, randomised, nonblinded study. A total of 151 patients were recruited; 133 (66 meropenem, 67 imipenem/cilastatin) were clinically evaluable and 84 (42 meropenem, 42 imipenem/cilastatin) bacteriologically evaluable. Most clinically evaluable patients (90%) were in intensive care units, required mechanical ventilation (72%), and had received previous antibiotic therapy (62%). The mean (+/- SD) APACHE II score was 15.2 (+/- 6.6) in the meropenem group and 17.8 (+/- 6.8) in the imipenem/cilastatin group. The primary infections were nosocomial lower respiratory tract infections (56% of patients), intra-abdominal infections (15%), septicaemia (21%), skin/skin structure infections (5%), and complicated urinary tract infections (3%); 35% of the patients had two or more infections. There was no significant difference between the meropenem and imipenem/cilastatin groups in the rates of satisfactory clinical (weighted percentage 87% vs. 74%) or bacteriological (weighted percentage 79% vs. 71%) response. There was a slightly higher rate of clinical success with meropenem against primary or secondary lower respiratory tract infection (89% vs. 76%). Drug-related adverse events occurred in 17% and 15% of meropenem and imipenem/cilastatin patients, respectively. Meropenem (1 g t.i.d.) was as efficacious as the same dose of imipenem/cilastatin in this setting, and both drugs were well tolerated.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carbapenems; Cilastatin; Cilastatin, Imipenem Drug Combination; Cross Infection; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Prospective Studies; Thienamycins

The clinical and bacteriological efficacy and safety of the antibiotics ceftazidime or imipenem/cilastatin in seriously ill patients with nosocomial infections were compared in a prospective, open, evaluator-blind, multicentre comparative trial. The study was performed in 26 European centres, the majority being intensive care units. Subjects were randomized to receive either ceftazidime 2 g bid or imipenem cilastatin 0.5 g qid given for at least five days after stratification for pneumonia, septicaemia or urinary tract infection (UTI). Three hundred and ninety-three patients with serious nosocomial infections (254 with pneumonia; 91 with septicaemia and 48 UTI were treated between February 1988 and January 1990 and their clinical and bacteriological response to antibiotic treatment assessed. There were no significant differences between ceftazidime and imipenem/cilastatin in clinical efficacy. The failure rates in evaluable patients were 22 and 26% in pneumonia, 23 and 19% in septicaemia and 0 and 5% respectively in those with UTI. Overall there was no significant difference between the two antibiotics for bacteriological response in the three infection strata. However, in patients with pneumonia ceftazidime was significantly more effective than imipenem/cilastatin in clearing patients of Pseudomonas spp.: 3/17 and 11/19 patients respectively had persistent growth of Pseudomonas spp. post-treatment (P = 0.004), and in one ceftazidime failure resistance emerged compared to six imipenem/cilastatin failures in which resistance emerged. Few drug-related adverse events were recorded in either treatment group. Monotherapy with either ceftazidime (2 g bid) or imipenem/cilastatin (0.5 g qid) is safe and effective and could be considered as an alternative to combination therapy for the treatment of serious hospital-acquired infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteria; Ceftazidime; Cilastatin; Cilastatin, Imipenem Drug Combination; Cross Infection; Drug Combinations; Female; Humans; Imipenem; Male; Middle Aged

Topics: Anti-Bacterial Agents; Bacteremia; Cilastatin; Cilastatin, Imipenem Drug Combination; Ciprofloxacin; Cross Infection; Drug Combinations; Drug Resistance, Multiple, Bacterial; Flavobacteriaceae Infections; Humans; Imipenem; Male; Middle Aged

A nosocomial outbreak of multi-drug-resistant Acinetobacter calcoaceticus-A. baumannii (MDR-ACB) complex infection occurred in a newly constructed building at a 2,500-bed tertiary medical center in Taiwan.. An investigation was carried out by molecular approaches to trace the bacteria. Antimicrobial susceptibilities, risk factors, and the occurrence of nosocomial MDR-ACB infections were investigated. From January to December 2009, 53 patients were infected with MDR-ACB, and 23 environmental surveys were performed in two surgical intensive care units (ICUs) within the new building. Forty-two clinical isolates were obtained from patients and 22 samples from nine environmental surveys.. Forty clinical isolates (95.2%) and 18 environmental samples (81.8%) were positive for MDR-ACB of type A, the predominant outbreak strain. This strain was identical to that isolated in an outbreak in the old hospital in 2006, as proved by repetitive extragenic palindromic-based polymerase chain reaction and pulsed-field gel electrophoresis. Although the outbreak isolates contained blaOXA-23-like and blaOXA-51-like genes, analysis of the antimicrobial susceptibilities demonstrated increases in resistance to cefepime and imipenem-cilastatin in MDR-ACB isolated in the later outbreak.. Not only patients or healthcare workers, but also medical equipment, might have carried the predominant outbreak strain from the old district to the new building. Therefore, even in a new environment, infection control programs must be enforced continually, and healthcare providers must be educated repeatedly to prevent recurrent outbreaks of MDR-ACB infection in the hospital setting.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Cefepime; Cephalosporins; Chi-Square Distribution; China; Cilastatin; Cilastatin, Imipenem Drug Combination; Critical Care; Cross Infection; Disease Outbreaks; Drug Combinations; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Imipenem; Microbial Sensitivity Tests; Public Health Surveillance; Retrospective Studies

Six years after initiating a monthly antibiotic cycling protocol in the surgical intensive care unit (SICU), we retrospectively reviewed antibiogram-derived sensitivities of predominant gram-negative pathogens before and after antibiotic cycling. We also examined susceptibility patterns in the medical intensive care unit (MICU) where antibiotic cycling is not practiced.. Antibiotic cycling protocol was implemented in the SICU starting in 2003, with monthly rotation of piperacillin/tazobactam, imipenem/cilastin, and ceftazidime. SICU antibiogram data from positive clinical cultures for years 2000 and 2002 were included in the pre-cycling period, and those from 2004 to 2009 in the cycling period.. Profiles of SICU pseudomonal isolates before (n = 116) and after (n = 205) implementing antibiotic cycling showed statistically significant improvements in susceptibility to ceftazidime (66% versus 81%; P = 0.003) and piperacillin/tazobactam (75% versus 85%; P = 0.021), while susceptibility to imipenem remained unaltered (70% in each case; P = 0.989). Susceptibility of E. coli isolates to piperacillin/tazobactam improved significantly (46% versus 83%; P < 0.0005), trend analysis showing this improvement to persist over the study period (P = 0.025). Similar findings were not observed in the MICU. Review of 2004-2009 antibiotic prescription practices showed monthly heterogeneity in the SICU, and a 2-fold higher prescribing of piperacillin/tazobactam in the MICU (P < 0.0001).. Six years into antibiotic cycling, we found either steady or improved susceptibilities of clinically relevant gram-negative organisms in the SICU. How much of this effect is from cycling is unknown, but the antibiotic heterogeneity provided by this practice justifies its ongoing use.

Topics: Anti-Bacterial Agents; Ceftazidime; Cilastatin; Cilastatin, Imipenem Drug Combination; Critical Care; Cross Infection; Drug Combinations; Drug Resistance, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Humans; Imipenem; Infection Control; Klebsiella Infections; Klebsiella pneumoniae; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Surgical Wound Infection

Plasma imipenem concentrations were measured in 19 critically ill children (median age, 0.8 year; range, 0.02 to 12.9 years). Wide interindividual variations (2 to 4x at peak and >10x at trough concentrations) resulted in unpredictable plasma levels in several children. To avoid subtherapeutic drug levels, we recommend treatment with at least 100 mg/kg of body weight/day of imipenem-cilastatin for critically ill children requiring such therapy.

Topics: Anti-Bacterial Agents; Area Under Curve; Bacterial Infections; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Critical Illness; Cross Infection; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Infant; Infant, Newborn; Infusions, Intravenous; Male

Enterobacter aerogenes strains resistant to imipenem were isolated in 10 patients, 7 of whom had received imipenem-cilastatin. The strains were differentiated by biotype, antibiotype, and plasmid content. All of the strains overproduced a chromosomal cephalosporinase and lost a major outer membrane protein with a size of about 40 kDa. In 5 of the 10 patients, E. aerogenes strains resistant to extended-spectrum cephalosporin were isolated during the same stay. In three patients, the similarity between the imipenem-susceptible and -resistant strains suggests the occurrence of mutation and reversion in vivo. The combination imipenem-cilastatin has been critically important for use with multiresistant strains of Enterobacter spp., but its use increases the risk of selection of imipenem-resistant strains.

Topics: Bacterial Outer Membrane Proteins; Bacterial Typing Techniques; beta-Lactamases; Cephalosporinase; Cilastatin; Cilastatin, Imipenem Drug Combination; Cross Infection; Drug Combinations; Drug Resistance, Microbial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Imipenem; Klebsiella pneumoniae; Microbial Sensitivity Tests; Plasmids

Topics: Anti-Bacterial Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Cross Infection; Cyclopropanes; Drug Combinations; Humans; Imipenem; Thienamycins

In an open prospective study the efficacy and tolerance of imipenem/cilastatin was investigated in 24 critically ill patients on mechanical ventilation with nosocomial respiratory tract infection. Nine patients had previously received antibiotic therapy, eight of them with various other beta-lactam antibiotics which had failed. Imipenem was given in a dose of 1-3 g/24 h over 5-37 (mean 11) days. Seven patients were additionally treated with aminoglycosides, one patient with erythromycin. Pseudomonas aeruginosa (n = 14), Staphylococcus aureus (n = 4), Haemophilus influenzae (n = 4) and Escherichia coli (n = 3) were the potential pathogens most frequently isolated from tracheo-bronchial secretions. All of the isolates were susceptible to imipenem. 91% of the infections without and 77% with involvement of P. aeruginosa were successfully treated. Two patients who had not responded to previous treatment succumbed to the consequences of progressive respiratory distress syndrome. All of the gram-positive and 85% of the gram-negative pathogens (Pseudomonas not included) were eliminated in the course of therapy. By contrast, 64% of the isolates of P. aeruginosa persisted; half of these became imipenem-resistant. Nine patients showed adverse reactions including one case of pseudomembranous colitis or laboratory abnormalities which were all reversible. Imipenem/cilastatin proved highly effective and was relatively well tolerated; it is suitable as a single agent for the initial treatment of nosocomial respiratory tract infections in ventilated patients, although only with limitations in cases of infection due to P. aeruginosa.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cross Infection; Cyclopropanes; Drug Combinations; Female; Humans; Imipenem; Male; Middle Aged; Prospective Studies; Respiration, Artificial; Respiratory Insufficiency; Respiratory Tract Infections; Thienamycins