cilastatin--imipenem-drug-combination and Peritonitis

Tigecycline, a first-in-class broad-spectrum glycylcycline antibiotic, has broad-spectrum in vitro activity against bacteria commonly encountered in complicated intra-abdominal infections (cIAIs), including aerobic and facultative Gram-positive and Gram-negative bacteria and anaerobic bacteria. In the current trial, tigecycline was evaluated for safety and efficacy vs. imipenem/cilastatin in hospitalized Chinese patients with cIAIs.. In this phase 3, multicenter, open-label study, patients were randomly assigned to receive IV tigecycline or imipenem/cilastatin for /=1 dose of study drug and comprised the modified intent-to-treat population. In the microbiologically evaluable population, 86.5% (45 of 52) of tigecycline- and 97.9% (47 of 48) of imipenem/cilastatin-treated patients were cured at the test-of-cure assessment (12-37 days after therapy); in the microbiologic modified intent-to-treat population, cure rates were 81.7% (49 of 60) and 90.9% (50 of 55), respectively. The overall incidence of treatment-emergent adverse events was 80.4% for tigecycline vs. 53.9% after imipenem/cilastatin therapy (P < 0.001), primarily due to gastrointestinal-related events, especially nausea (21.6% vs. 3.9%; P < 0.001) and vomiting (12.4% vs. 2.0%; P = 0.005).. Clinical cure rates for tigecycline were consistent with those found in global cIAI studies. The overall safety profile was also consistent with that observed in global studies of tigecycline for treatment of cIAI, as well as that observed in analyses of Chinese patients in those studies; no novel trends were observed.. ClinicalTrials.gov NCT00136201.

Topics: Adult; Aged; Anti-Bacterial Agents; Asian People; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Male; Middle Aged; Minocycline; Peritonitis; Tigecycline; Treatment Outcome

Complicated intra-abdominal infections (cIAI) remain challenging to treat because of their polymicrobial etiology including multi-drug resistant bacteria. The efficacy and safety of tigecycline, an expanded broad-spectrum glycylcycline antibiotic, was compared with imipenem/cilastatin (IMI/CIS) in patients with cIAI.. A prospective, double-blind, multinational trial was conducted in which patients with cIAI randomly received intravenous (IV) tigecycline (100 mg initial dose, then 50 mg every 12 hours [q12h]) or IV IMI/CIS (500/500 mg q6h or adjusted for renal dysfunction) for 5 to14 days. Clinical response at the test-of-cure (TOC) visit (14-35 days after therapy) for microbiologically evaluable (ME) and microbiological modified intent-to-treat (m-mITT) populations were the co-primary efficacy endpoint populations.. A total of 825 patients received >or= 1 dose of study drug. The primary diagnoses for the ME group were complicated appendicitis (59%), and intestinal (8.8%) and gastric/duodenal perforations (4.6%). For the ME group, clinical cure rates at TOC were 80.6% (199/247) for tigecycline versus 82.4% (210/255) for IMI/CIS (95% CI -8.4, 5.1 for non-inferiority tigecycline versus IMI/CIS). Corresponding clinical cure rates within the m-mITT population were 73.5% (227/309) for tigecycline versus 78.2% (244/312) for IMI/CIS (95% CI -11.0, 2.5). Nausea (31.0% tigecycline, 24.8% IMI/CIS [P = 0.052]), vomiting (25.7% tigecycline, 19.4% IMI/CIS [P = 0.037]), and diarrhea (21.3% tigecycline, 18.9% IMI/CIS [P = 0.435]) were the most frequently reported adverse events.. This study demonstrates that tigecycline is as efficacious as imipenem/cilastatin in the treatment of patients with cIAI.

Topics: Abdomen; Adult; Anti-Bacterial Agents; Appendicitis; Bacterial Infections; Cholecystitis; Cilastatin; Cilastatin, Imipenem Drug Combination; Diverticulitis; Double-Blind Method; Drug Combinations; Female; Humans; Imipenem; Intestinal Perforation; Male; Middle Aged; Minocycline; Peptic Ulcer Perforation; Peritonitis; Tigecycline

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

Topics: Adult; Cilastatin; Cilastatin, Imipenem Drug Combination; Combined Modality Therapy; Cost-Benefit Analysis; Debridement; Drug Combinations; Drug Therapy, Combination; Humans; Imipenem; Microbial Sensitivity Tests; Peritonitis; Survival Rate; Treatment Outcome

Imipenem/cilastatin sodium is a new thienamycin class of antibiotic with a broad spectrum of bactericidal activities. It may be a suitable single first-line therapy for the treatment of peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients. Fifty episodes of CAPD peritonitis were treated with imipenem/cilastatin sodium. On presentation, all patients were given an intravenous loading dose of 1 g of imipenem/cilastatin sodium followed by intraperitoneal imipenem/cilastatin sodium for 10 days. During 1989 (30 episodes), 20 mg imipenem/cilastatin sodium was added to each 2-liter bag of peritoneal dialysis (PD) fluid for 10 days. The primary response rate as defined by polymorphonuclear neutrophils < 100/ml in PD fluid was 90%. Unfortunately, 17% of the peritonitis relapsed within 14 days of stopping antibiotic. The complete cure rate without relapse was therefore 73%. During 1990 (20 episodes), 100 mg imipenem/cilastatin sodium was added to each 2-liter bag of PD fluid for 10 days. The primary response rate was 95%, the complete cure rate without relapse was 85%. Imipenem/cilastatin sodium is an effective single first-line antibiotic for the treatment of peritonitis in CAPD.

Topics: Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Humans; Imipenem; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Staphylococcal Infections; Time Factors

A multi-center clinical study was carried out at the first Department of Surgery, Okayama University Medical School and its affiliated institutions to evaluate the efficacy and safety profiles of intramuscular imipenem/cilastatin sodium (IPM/CS) in surgical infections, which were mainly biliary tract infections and peritonitis. The following results were obtained: 1. The efficacy rate was 72.0% in a total of 25 evaluable patients and 81.8% in patients with cholecystitis. 2. The efficacy rates in patients with and without underlying diseases were 70.0% and 73.3%, respectively, and they were 71.4% in patients with mild or moderate infections and 75.0% in patients with severe infections. 3. Bacteriologically, the eradication rate was 100% for Gram-positive bacteria and 62.5% for Gram-negative bacteria, with an overall eradication rate of 78.6%. The eradication rate for monomicrobial infections was 71.4% and that for polymicrobial infections was 100%. 4. Out of 25 patients, one developed diarrhea as a drug-related adverse reaction, and laboratory abnormalities attributable to the treatment were observed in 5 patients. None of them was serious, however. 5. The overall usefulness rate was 60.0%, and the usefulness for cholecystitis (72.7%) was superior to that for cholangitis (33.3%).

Topics: Adult; Aged; Cholangitis; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Injections, Intramuscular; Male; Microbial Sensitivity Tests; Middle Aged; Peritonitis; Postoperative Complications

We designed a multicenter study to compare tobramycin/clindamycin to imipenem/cilastatin for intra-abdominal infections. We included the Acute Physiology and Chronic Health Evaluation (APACHE II) index of severity and excluded patients without established infection. Two hundred ninety patients were enrolled, of whom 162 were evaluable. Using logistic regression to analyze both outcome at the abdominal site of infection and outcome as mortality, we found a significant correlation for both with APACHE II score (p less than 0.0001 for both). Next we analyzed the residual effect of treatment assignment and found a significant improvement in outcome for imipenem/cilastatin-treated patients (p = 0.043). The differences in outcome were explained by a higher failure rate for patients with gram-negative organisms for tobramycin/clindamycin-treated patients (p = 0.018). This was reflected in a significantly higher incidence of fasciitis requiring reoperation and prosthetic fascial replacement. Maximum peak tobramycin levels were analyzed for 63 tobramycin/clindamycin patients harboring gram-negative organisms. For failures the maximum peak was 6.4 +/- 1.9 micrograms/mL, and time to maximum peak was 4.6 +/- 5.2 days. For successes the maximum peak was 6.1 +/- 1.7 micrograms/mL, occurring at 3.8 +/- 2.6 days. This study supports inclusion of severity scoring in statistical analyses of outcome results and supports the notion that imipenem/cilastatin therapy improves outcome at the intra-abdominal site of infection as compared to a conventionally prescribed amino-glycoside-based regimen.

Topics: Abscess; Adult; Aged; Anti-Bacterial Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Clindamycin; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Middle Aged; Peritonitis; Prospective Studies; Severity of Illness Index; Tobramycin

Imipenem/cilastatin at a dose of 0.5 g six hourly was compared to conventional combination therapy with ampicillin 0.5 g six hourly, metronidazole 0.5 g eight hourly and gentamicin 80 mg eight hourly (with dose adjustment by trough and peak serum levels) in the treatment of severe intra-abdominal infections. All antibiotics were given intravenously. Forty-five patients entered the trial. Of the 19 evaluable patients in the imipenem/cilastatin group, 16 were clinically cured with five microbiological successes and two failures. Of 24 evaluable patients in the combination group, 22 were clinically cured with one microbiological success and one failure. One patient in each group suffered an adverse effect. Patients in the I/C group tended to be older with more women and more severe infections. The origin of peritonitis was similar. I/C did not differ from combination therapy in efficacy or safety and was comparable in cost. However, I/C was easier to administer than combination therapy and there was no need for serum concentration monitoring.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Cyclopropanes; Drug Combinations; Drug Therapy, Combination; Female; Gentamicins; Humans; Imipenem; Male; Metronidazole; Middle Aged; Peritonitis; Random Allocation; Thienamycins

Topics: Aged; Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials as Topic; Drug Combinations; Female; Gentamicins; Humans; Imipenem; Male; Metronidazole; Peritonitis

A lethal peritonitis model was induced in mice with a Klebsiella pneumoniae isolate producing the carbapenemase OXA-48. Administration of a single dose (up to 100 mg/kg) of the antibiotic piperacillin-tazobactam, imipenem-cilastatin, ertapenem, or cefotaxime had little or no impact on lethality. Ceftazidime had the highest efficacy in vivo, which mirrored its in vitro activity; this was not the case for carbapenems. Therefore, ceftazidime may be recommended for the treatment of infections due to OXA-48 producers if they do not coproduce an extended-spectrum β-lactamase or a plasmid-mediated AmpC cephalosporinase.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Cefotaxime; Ceftazidime; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Ertapenem; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Lethal Dose 50; Mice; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Plasmids; Survival Rate

Topics: Amikacin; Anti-Bacterial Agents; Antibiotic Prophylaxis; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Enterococcus; Female; Gastroscopy; Gynecological Examination; Humans; Imipenem; Middle Aged; Peritoneal Dialysis; Peritonitis; Secondary Prevention; Treatment Outcome; Vancomycin

In this report of the OPTAMA (Optimizing Pharmacodynamic Target Attainment using the MYSTIC Antibiogram) program, we utilized Monte Carlo simulation to compare the probabilities of achieving bactericidal time above the minimum inhibitory concentration (MIC) (%T > MIC) exposures for imipenem-cilastatin 500 mg q6h and 1000 mg q8h, meropenem 500 mg q6h and 1000 mg q8h and piperacillin/tazobactam 3.375 g q6h and 4.5 g q8h in the empiric treatment of secondary peritonitis.. The prevalence of pathogens causing secondary peritonitis was identified from the primary surgical and infectious diseases literature. Data for these pathogens with respect to MIC were obtained from the 2003 MYSTIC surveillance study and weighted by the prevalence of each pathogen. A sensitivity analysis varying the prevalence of P. aeruginosa was performed with two additional models to determine the robustness of the data. Pharmacokinetic parameters, obtained from previously published studies in healthy volunteers were used to simulate the %T > MIC for 10,000 patients receiving imipenem-cilastatin, meropenem, and piperacillin/tazobactam. The likelihood of obtaining bactericidal exposure is reported.. Empiric utilization of imipenem-cilastatin and meropenem 500 mg q6h and 1000 mg q8h regimens achieved 99.6%-99.7% likelihood of bactericidal exposure. Piperacillin/ tazobactam 3.375 g q6h and 4.5 g q8h produced bactericidal target attainments of 92.9% and 85.2%, respectively. Models simulating higher prevalence of P. aeruginosa reduced the likelihood of bactericidal exposure for piperacillin/tazobactam regimens significantly and had little effect on the carbapenems.. All of the beta-lactams used in the current analysis were predicted to achieve high target attainment consistently for the empiric treatment of secondary peritonitis. However, imipenem-cilastatin 500 mg q6h and 1000 mg q8h, meropenem 1000 mg q8h and 500 mg q6h, and piperacillin/tazobactam 3.375 g q6h achieved the highest likelihood. These, in particular, would be effective choices for the empiric treatment of secondary peritonitis.

Topics: Anti-Bacterial Agents; beta-Lactams; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Models, Biological; Monte Carlo Method; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibiotic Prophylaxis; Cilastatin; Cilastatin, Imipenem Drug Combination; Diabetic Foot; Drug Combinations; Female; Humans; Imipenem; Male; Middle Aged; Pancreatitis, Acute Necrotizing; Peritonitis; Postoperative Care; Protease Inhibitors; Suppuration; Thienamycins

The present study addressed the role of IL-12 in a murine model of septic peritonitis, induced by cecal ligation and puncture (CLP). Although CLP surgery induced IL-12 production at 6 and 24 h after surgery, IL-12 immunoneutralization was clearly deleterious in this model: 54% of CLP mice receiving preimmune serum survived, whereas mice administered IL-12 antisera prior to CLP experienced a 25% survival rate. IL-12 immunoneutralization not only led to increased mortality, but also appeared to promote a shift away from IL-12 and IFN-gamma, in favor of IL-10. This cytokine shift corresponded to changes in bacterial load, as CLP mice receiving IL-12 antiserum yielded more CFUs from the peritoneal cavity at 24 h after CLP. To address the role of bacterial infection in IL-12 antiserum-induced mortality following CLP, antibiotics were administered for 4 days after surgery. Despite regular antibiotic administration, IL-12 immunoneutralization still reduced survival in CLP mice. Furthermore, histology of the ceca revealed that mice administered IL-12 antisera failed to show typical organization of the damaged cecum wall. Accordingly, Gram staining revealed bacteria within peritoneal fluids from these mice, while peritoneal fluids from CLP mice that received preimmune serum and antibiotics were free of bacteria. Altogether, these data suggested multiple important roles for IL-12 in the evolution of murine septic peritonitis.

Topics: Acute Disease; Animals; Cecal Diseases; Cilastatin; Cilastatin, Imipenem Drug Combination; Disease Models, Animal; Drug Combinations; Drug Therapy, Combination; Female; Fibrosis; Imipenem; Immune Sera; Immunization, Passive; Interferon-gamma; Interleukin-10; Interleukin-12; Intestinal Perforation; Ligation; Mice; Peritoneum; Peritonitis; Sepsis; Wound Healing

To study the therapeutic effects of volume support, antibiotics, and a monoclonal antiendotoxin antibody on the mortality rate and blood concentrations of endothelin and other mediators in fulminant intra-abdominal sepsis in rats.. Prospective, randomized, controlled trial.. Research laboratory in a university hospital.. Adult male Wistar rats.. Fulminant polymicrobial intra-abdominal sepsis was induced by a 4-mm cecal perforation. Treatment was performed with saline volume support, the antibiotic imipenem/cilastatin, and the monoclonal antiendotoxin antibody E5, both as monotherapy and as a combined regimen. Mortality rates were recorded and concentrations of bacteria, endotoxin, tumor necrosis factor (TNF), big endothelin, and endothelin-1 (21 amino acids) in blood were determined.. Substantial increases in circulating big endothelin and endothelin-1 concentrations were observed during sepsis. The combination of volume support with antibiotics reduced the mortality rate, but neither as monotherapy nor as a combined regimen did this intervention modify plasma endothelin-1 concentrations. This finding suggests that hypovolemia and bacteria per se are not important stimuli for endothelin synthesis and a high plasma level of endothelin-1 does not necessarily predict poor outcome in sepsis. The inactive big endothelin is enzymatically cleaved, leaving the biologically active 21-residue endothelin-1. Intervention with E5 substantially reduced the mortality rate and concentrations of endotoxin, TNF, and plasma endothelin-1, while big endothelin and total endothelin immunoreactivity did not decrease. This finding indicates a suppressed conversion of big endothelin to endothelin-1 after E5 treatment. Because E5 has no direct effect on endothelin metabolism, E5 probably reduces the synthesis of endothelin-1 by suppressing the endothelin-activators endotoxin and TNF. A triple combination of volume support, imipenem/cilastatin, and E5 was the only regimen that reduced all of the end points: mortality rate, hemoconcentration, bacteria, endotoxin, TNF, and endothelin-1.. The concentration of plasma endothelin was increased during fulminant intra-abdominal sepsis in rats. Combining volume support with antibiotic therapy reduced the mortality rate, but did not modify concentrations of plasma endothelin-1. The monoclonal antiendotoxin antibody E5 reduced the mortality rate and concentrations of endotoxin, TNF, and endothelin-1, but not big endothelin. This finding indicates that E5 therapy inhibits the conversion of big endothelin to 21-residue endothelin-1.

Topics: Animals; Antibodies, Monoclonal; Blood Volume; Cilastatin; Cilastatin, Imipenem Drug Combination; Combined Modality Therapy; Drug Combinations; Drug Evaluation, Preclinical; Drug Therapy, Combination; Endothelins; Fluid Therapy; Imipenem; Immunoglobulins; Male; Peritonitis; Prospective Studies; Random Allocation; Rats; Rats, Wistar; Sepsis; Time Factors

Topics: Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Humans; Imipenem; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis

Inhibition of nitric oxide synthesis was investigated in a murine model of advanced sepsis in which antibiotic therapy alone did not improve survival. Seven hours after receiving a lethal intraperitoneal challenge with live Escherichia coli, mice were given either NG-monomethyl-L-arginine (L-NMMA) intravenously, imipenem-cilastatin subcutaneously or a combination of both. L-NMMA (3-300 mg/kg) or imipenem-cilastatin (10 or 50 mg/kg) given alone did not improve survival; co-administration of L-NMMA and either 10 or 50 mg imipenem-cilastatin/kg improved survival significantly. These findings suggest that nitric oxide contributes to the morbidity associated with advanced sepsis and that nitric oxide synthase inhibition may improve the efficacy of conventional antimicrobial treatment of severe infections.

Topics: Amino Acid Oxidoreductases; Animals; Arginine; Cilastatin; Cilastatin, Imipenem Drug Combination; Disease Models, Animal; Drug Combinations; Drug Therapy, Combination; Escherichia coli Infections; Imipenem; Male; Mice; Nitric Oxide Synthase; omega-N-Methylarginine; Peritonitis

CAPD peritonitis is most commonly due to gram positive infection. Gram negative bacillary infection is less frequent but is often seen in hospitalized patients or in those on antibiotics. Weeksella virosa (formerly known as Flavobacterium II F) has been isolated from the vaginal secretions and urine of normal women. As gram negative colonization typically proceeds from the perineal region, Weeksella virosa peritonitis might be expected in women at risk for gram negative peritonitis. A 33-year-old woman on CAPD developed multiply resistant Weeksella virosa peritonitis after prior hospitalization for pericarditis and antibiotic treatment for pneumonia. Cultures became negative and cell counts returned to normal during treatment with intravenous imipenem/cilastin. Curative treatment was completed with intraperitoneal imipenem/cilastin and oral ampicillin. Treatment was well tolerated despite theoretical concerns about the risk of seizures in patients with severe renal insufficiency not on hemodialysis.

Topics: Adult; Anti-Bacterial Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Gram-Negative Bacterial Infections; Humans; Imipenem; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis

Calculated chemotherapy is based on the knowledge of the typical bacterial agents of a particular infection. From January 1983 to August 1985 bacteriological findings from surgical patients with peritonitis, septicemia or pneumonia treated in an intensive care unit were analysed. The study concentrated on those findings only which differed from previous bacteriological investigations. During the first three days 53 patients on assisted ventilation suffering from peritonitis exhibited mainly enterobacteria in their peritoneal secretions. At day 10 or later we also found bacteria from the pseudomonas group. At that time the bacterial spectrum of bronchial secretions was comparable to that of the peritoneal secretions of the same patient. After day 10, the bacterial spectrum was similar in 36 ventilated patients without peritonitis, in 56 patients suffering from post-operative pneumonia and in peritonitis patients. According to our findings, calculated chemotherapy may be based on the fact that patients with peritonitis who cannot be cured within a few days have a bacterial flora comparable to that of patients with septicemia or pneumonia. Patients with severe infections following surgery, such as potentially fatal pneumonia, generalised peritonitis or septicemia were treated with imipenem/cilastatin, according to the above definitions of calculated chemotherapy. 37 of 46 patients treated between May and December 1985, were clinically cured. Microorganisms persisted in five clinically cured patients. Development of resistance to imipenem was observed in one case. In one case treatment had to be stopped because of an allergic skin reaction. Monotherapy of peritonitis by imipenem/cilastatin appeared more satisfactory than treatment with combinations of other antibiotics.

Topics: Adult; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cyclopropanes; Drug Combinations; Female; Humans; Imipenem; Male; Middle Aged; Peritonitis; Pneumonia; Postoperative Complications; Respiration, Artificial; Retrospective Studies; Sepsis; Thienamycins