cilastatin--imipenem-drug-combination and Escherichia-coli-Infections

Endocarditis due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae is a rare but challenging condition. Its treatment relies on carbapenems alone or in combination, and no alternative has been described to date. The cephamycin cefoxitin has been used for treatment of mild ESBL-producing Enterobacteriaceae infections.. We report two patients with nosocomial endocarditis due to ESBL-producing Escherichia coli and Klebsiella pneumoniae who underwent clinical failure or adverse event, respectively, during treatment with imipenem-cilastatin. The first patient was subsequently treated with cefoxitin combined with ciprofloxacin with a favorable outcome. In the second patient, the endocarditis relapsed following a 6-week treatment with cefoxitin and fosfomycin. In time-kill assays, the cefoxitin/ciprofloxacin and cefoxitin/fosfomycin combinations showed synergistic effect.. These cases illustrate that cefoxitin is an interesting alternative to carbapenems, even in severe infections such as endocarditis. Pharmacokinetic optimization and combination with another synergistic antibiotic should be considered whenever possible.

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cefoxitin; Cilastatin, Imipenem Drug Combination; Ciprofloxacin; Endocarditis; Enterobacteriaceae; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Urinary Tract Infections

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

An ertapenem-resistant Escherichia coli isolate was recovered from peritoneal fluid in a patient who had been treated with imipenem/cilastatin for 10 days. Ertapenem resistance may be explained by a defect in the outer membrane protein and production of extended-spectrum beta-lactamase CTX-M-2.

Topics: Anti-Bacterial Agents; Antifungal Agents; beta-Lactams; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Resistance, Multiple, Bacterial; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Fluconazole; Gentamicins; Humans; Imipenem; Immunocompromised Host; Middle Aged; Vancomycin

To study the effect of moxifloxacin versus imipenem/cilastatin (hereafter referred to as imipenem) treatment on the mortality of mice infected intravenously with different strains of Bacteroides fragilis and Escherichia coli.. Groups of 20 mice each were infected intravenously with different strains of B. fragilis [moxifloxacin and imipenem susceptible or resistant, and enterotoxin (ET) positive or negative] and E. coli (moxifloxacin and imipenem susceptible). Twenty-four hours post-infection, intravenous therapy with either moxifloxacin (2.0 mg twice a day) or imipenem (2.4 mg three times a day) was started and continued for 3 days. Control groups were left untreated. Survival rates were recorded at day 7 post-infection. At that time, surviving mice were killed and numbers of bacteria in the liver and kidneys were determined.. If compared with untreated animals, mice treated with either moxifloxacin or imipenem showed significantly improved survival (P < 0.001). There was no significant difference (P = 0.97) in the survival rates comparing the two treatment regimens irrespective of the ET positivity or the susceptibility to moxifloxacin or imipenem of the infective B. fragilis strain. However, there was a tendency that B. fragilis was recovered more often from the liver and kidneys of mice infected with ET positive strains.. The data show that moxifloxacin was as efficacious as imipenem in reducing the mortality rate of mice suffering from a severe systemic aerobic/anaerobic infection.

Topics: Animals; Anti-Bacterial Agents; Aza Compounds; Bacteroides fragilis; Bacteroides Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; DNA, Bacterial; Drug Combinations; Escherichia coli; Escherichia coli Infections; Female; Fluoroquinolones; Imipenem; Kidney; Liver; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Microbial Sensitivity Tests; Moxifloxacin; Quinolines; Reverse Transcriptase Polymerase Chain Reaction

Although septic shock has a high mortality rate of 43%, recently the endotoxin adsorption column was established and its efficacy is interesting. We report a very effective case of endotoxin adsorption the rapy for septic shock due to acute pyelonephritis. A 59-year-old man with chief complaints of pyrexia and right backache was referred to our hospital with a small right ureteral stone (4 mm) associated with a low degree of right hydronephrosis. Since it was diagnosed as right acute pyelonephritis, antibiotics were administered; and then septic shock occurred on the day of hospitalization. Endotoxin adsorption therapy was performed for two days and hemodynamic stability was achieved. The concentration of blood endotoxin was reduced remarkably and the efficacy of endotoxin adsorption therapy was suggested.

Topics: Acute Disease; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Endotoxins; Escherichia coli; Escherichia coli Infections; Hemofiltration; Humans; Imipenem; Male; Middle Aged; Pyelonephritis; Shock, Septic; Sorption Detoxification; Treatment Outcome; Ureteral Calculi

An 84-year-old male presented to the emergency room with the chief complaint of painful, swollen penis following the use of a constriction ring to maintain penile erection. A high fever, chills and hypotension were recognized. Septic shock was presumed, and administration of antibiotics was started. Microbiologic cultures revealed Escherichia coli in blood. We herein report a rare but serious complication accompanying incarceration of the penis.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Inflammatory Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Escherichia coli Infections; gamma-Globulins; Humans; Imipenem; Male; Methylprednisolone; Minocycline; Penis; Shock, Septic

We report herein the case of a 40-year-old man with AIDS who was admitted to hospital with severe abdominal pain, fever, and chills. He underwent an emergency laparotomy which revealed a perforated appendix with suppurative peritonitis. An appendectomy with peritoneal drainage was carried out, but the postoperative course was complicated by fever without leukocytosis; however, he gradually improved following treatment with intravenous antibiotics, granulocyte colony-stimulating factor (G-CSF) and immunoglobulins, and made a complete recovery. His postoperative course demonstrates the effectiveness of this treatment regimen for patients with AIDS complicated by infection without an increase in the white blood cell count (WBC).

Topics: Acute Disease; Adult; AIDS-Related Opportunistic Infections; Appendectomy; Appendicitis; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Escherichia coli Infections; Fever of Unknown Origin; Granulocyte Colony-Stimulating Factor; Humans; Imipenem; Immunization, Passive; Intestinal Perforation; Male; Postoperative Complications; Rupture, Spontaneous

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

We describe a case of bilateral emphysematous pyelonephritis, in a diabetic female, that responded to medical therapy alone. Her complete improvement is documented radiologically. Emphysematous pyelonephritis, as a cause of serious infection in diabetic patients, is briefly reviewed.

Topics: Cilastatin; Cilastatin, Imipenem Drug Combination; Ciprofloxacin; Drug Combinations; Emphysema; Escherichia coli Infections; Female; Humans; Imipenem; Middle Aged; Pyelonephritis; Tomography, X-Ray Computed

A study was performed to assess the effect of parenteral administration of imipenem on the intestinal microbial ecology of mice in relation to the therapeutic efficacy of the drug. The therapeutic effect of imipenem was assessed in a short-term experimental thigh muscle infection with Escherichia coli in irradiated mice. The maximum antibacterial effect of imipenem was approached at a single dose of 80 mg/kg. At this dose of imipenem the number of viable E. coli in the thigh muscle decreased from 9 x 10(6) to 4 x 10(5), whereas in untreated controls this number increased from 9 x 10(6) to 2 x 10(8). Daily administration of a dose of 80 mg/kg imipenem caused significant changes in the intestinal flora of conventional mice, despite the low concentrations of the drug (about 1 mg/kg) found in the caecum 30 min after infection of this dose. These changes consisted of an increase in the number of E. coli and enterococci and a decrease in the number of Staphylococcus aureus in the faeces. Furthermore, at this dose of imipenem, the number of Candida albicans recovered from the faeces after oral contamination with this organism was increased. We conclude from these animal experiments that the use of imipenem in high doses causes ecological changes in the intestinal bacterial flora with the potential to promote colonization by candida.

Topics: Animals; Cilastatin; Cilastatin, Imipenem Drug Combination; Colony Count, Microbial; Drug Combinations; Escherichia coli Infections; Imipenem; Injections, Subcutaneous; Intestines; Male; Mice; Muscular Diseases; Specific Pathogen-Free Organisms; Thigh

Cefamandole, cefoxitin, cefotetan, ceftizoxime, imipenem plus cilastatin, and ampicillin plus sulbactam were compared in the eradication of subcutaneous abscess in mice caused by Bacteroides fragilis group organisms and Escherichia coli alone or in combination. The abscesses were examined 5 d after inoculation. B. fragilis group reached log10.1-11.0 organisms per abscess and E. coli log11.6-12.5. Imipenem plus cilastatin significantly reduced (in 6.9-10.6 logs) the number of E. coli and all members of B. fragilis group alone or in all combinations. Ampicillin plus sulbactam reduced the numbers of all B. fragilis group (in 4.2-7.2 logs) but was less effective against E. coli (reduction of 1.8-4.2 logs). Cefoxitin was effective in significantly reducing (in 4.9-6.2 logs) the number of E. coli and all members of B. fragilis group alone or in all combinations. Cefotetan was effective against B. fragilis (reduction of 5.1-6.6 logs) and E. coli alone or in combination but did not reduce the number of Bacteroides thetaiotaomicron, Bacteroides vulgatus, and Bacteroides ovatus. Ceftizoxime was effective against only B. ovatus (reduction of 3.7-5.8) and E. coli (reduction of 6.0-8.1 logs); it did not reduce the number of other organisms. Cefamandole was effective against only E. coli and was not effective against any member of the B. fragilis group. These in vivo data confirm the in vitro activity of these antimicrobials.

Topics: Abscess; Ampicillin; Animals; Anti-Bacterial Agents; Bacteroides fragilis; Bacteroides Infections; Cefamandole; Cefotetan; Cefoxitin; Ceftizoxime; Cilastatin; Cilastatin, Imipenem Drug Combination; Disease Models, Animal; Drug Combinations; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Imipenem; Male; Mice; Skin Diseases; Sulbactam