cilastatin--imipenem-drug-combination and Bacteremia

In order to investigate the effect of carbapenems on systemic endotoxemia, 20 patients with severe sepsis due to ventilator-associated pneumonia and Gram-negative bacteremia were enrolled; 10 (group A) were administered 1 g t.i.d. of imipenem/cilastatin and 10 (group B) 2 g t.i.d. of meropenem. Blood was sampled at 0 time and after 1, 2, 4, 6, 12, 24, 36, 48, 60, 72, 84 and 96 hours for detection of endotoxins (LPS), interleukin-6 (IL-6), C-reactive protein (CRP) and drug levels. LPS were determined by the QCL-1000 LAL assay, IL-6 by an enzymeimmunoassay, CRP by nephelometry and carbapenem levels by a microbiological assay. We did not find that carbapenems had any effect on the kinetics of LPS and CRP; IL-6 of group A was lower than group B at 72 and 84 hours. No correlation was observed between drug levels of any carbapenem and LPS, IL-6 or CRP. It is concluded that in septic patients with Gram-negative bacteremia administration of either imipenem or meropenem did not affect systemic endotoxemia. The above data support the safe administration of both carbapenems in patients with severe sepsis.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; C-Reactive Protein; Carbapenems; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Endotoxemia; Female; Gram-Negative Bacterial Infections; Humans; Imipenem; Interleukin-6; Lipopolysaccharides; Male; Middle Aged; Pneumonia, Ventilator-Associated; Sepsis

An open, randomized, multinational, multicentre study was conducted to compare the efficacy, safety and tolerability of levofloxacin 500 mg twice daily with imipenem/cilastatin 1 g iv three-times daily in the treatment of hospitalized adult patients with clinically suspected bacteraemia/ sepsis. Levofloxacin patients could change from iv to oral administration after a minimum of 48 h iv treatment if clinical signs and symptoms of sepsis had improved. The primary efficacy analysis was based on the clinical and bacteriological response at clinical endpoint. A total of 503 patients were randomized and 499 included in the intent-to-treat population. The per-protocol population comprised 287 patients with bacteriologically proven infection. Clinical cure rates at clinical endpoint in the intent-to-treat population and per-protocol population were 77% (184/239) and 89% (125/140), respectively, for levofloxacin and 68% (178/260) and 85% (125/147), respectively, for imipenem/cilastatin. At follow-up, the cure rates in the per-protocol population were 84% for levofloxacin and 69% for imipenem/cilastatin. The 95% confidence interval for both populations showed that levofloxacin was as effective as imipenem/cilastatin. A satisfactory bacteriological response was obtained in 87% (96/110) of levofloxacin patients and 84% (97/116) of imipenem/cilastatin patients at clinical endpoint. Adverse events possibly related to the study drug were reported in 74 (31%) levofloxacin patients and 79 (30%) imipenem/cilastatin patients. There were no clinically appreciable differences between the treatment groups. Levofloxacin 500 mg twice daily, either iv or as sequential iv/oral therapy, was as effective and well tolerated as imipenem/cilastatin 1 g iv three-times daily in the treatment of hospitalized patients with suspected bacteraemia/sepsis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Bacteremia; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Imipenem; Levofloxacin; Middle Aged; Ofloxacin; Protease Inhibitors; Sepsis; Thienamycins

Therapeutic efficacy of the combined regimen, imipenem/cilastatin (IPM/CS) plus vancomycin (VCM), was examined in a total of 13 patients infected with MRSA (10 patients with pneumonia, 2 with sepsis and 1 with urinary tract infection). Based on the results of determination of FIC indices, in vitro combined effects were synergistic in 4 strains and additive in 3 strains. There was, however, no apparent correlation between the in vitro combined effect in terms of FIC index and clinical outcome. No side effects or abnormal laboratory findings were observed. The average daily doses of IPM/CS and VCM were 1.2 g and 1.25 g and the average administration periods were 17.5 and 14.9 days, respectively. The present results suggested that simultaneous use of IPM/CS and VCM at the standard doses could yield an enhancement of both bacteriological and clinical efficacies in treatment of the patients with MRSA infection.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Synergism; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Methicillin Resistance; Middle Aged; Pneumonia, Staphylococcal; Staphylococcal Infections; Urinary Tract Infections; Vancomycin

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

To compare the clinical efficacy between salvage antimicrobial regimen consisting of tigecycline plus extended-infusion imipenem/cilastatin (TIC) and regimen of sulbactam plus imipenem/cilastatin (SIC) for patients with ventilator-associated pneumonia and pneumonic bacteremia due to extensively drug-resistant (XDR) Acinetobacter baumannii (Ab) isolates, and determine the correlation of results of in vitro tigecycline-imipenem synergy test with clinical efficacy.. The comparative survey was conducted at a medical center in Taiwan in 2013. Patients comprising the TIC group (n = 28) received tigecycline plus extended-infusion imipenem/cilastatin following unresponsiveness to 3-day sulbactam-imipenem/cilastatin therapy, and those in the SIC group (n = 56) received sulbactam-imipenem/cilastatin throughout the course. Univariate and multivariate analyses were applied to explore 30-day case-fatality independent predictors. Additionally, the checkerboard test and time-kill analysis were performed for the bloodstream XDR-Ab isolates from patients in the TIC group, and molecular characterization was done for the bloodstream XDR-Ab strains of all patients.. We found that the TIC scheme has a significant benefit on improving patients' survival status (the mortality rate of TIC and SIC group patients was 14.3% and 64.3%, respectively), corresponding well with in vitro synergy or additivity results by the checkerboard test. Twenty TIC group cases had monomicrobial XDR-Ab cultured from tracheal aspirates after 10 days of tigecycline-imipenem/cilastatin therapy, but none developed subsequent pneumonia. However, breakthrough primary Burkholderia cepacia (n = 3) and Pseudomonas aeruginosa (n = 1) bacteremias were attributed to four TIC case fatalities. Shock, SIC regimen usage, and development of breakthrough bacteremia were independent predictors of 30-day in-hospital mortality.. Although the TIC regimen showed good efficacy, its value regarding managing XDR-Ab ventilator-associated pneumonia bacteremia needs further evaluation.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Hospital Mortality; Humans; Imipenem; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Salvage Therapy; Sulbactam; Taiwan; Tigecycline; Treatment Outcome

There have been few coherent reports on extraintestinal infection or bacteremia caused by Campylobacter jejuni (C. jejuni) or C. coli in Japan. To clarify the clinical and microbiological characteristics of invasive infections caused by these two species, we retrospectively analyzed the records of patients from whom these pathogens had been isolated from sterile sites between 2000 and 2015. During this study period, we identified 9 patients. The clinical syndrome of all of these patients was bacteremia. Three patients had underlying diseases with both liver cirrhosis and malignant neoplasm, and all of these patients were aged 60 years or older. The remaining 6 patients were immunocompetent and younger than 40 years of age. All 9 patients had a fever of 38.5 degrees C or higher. The proportion of patients with gastrointestinal symptoms was lower for the 3 patients with underlying diseases, compared with the 6 patients without underlying diseases (1/3 cases vs, 4/6 cases). Of the 8 strains evaluated for antimicrobial susceptibility, all were susceptible to imipenem/cilastatin, kanamycin and erythromycin, and 2 were resistant to levofloxacin. Antimicrobial treatment was administered to 8 patients, but one spontaneously recovered without any treatment. We were able to follow the outcomes of 8 patients, and all of these patients completely recovered without relapses. We also reviewed 14 Japanese patients reported in the Japanese and English literature and found similar clinical features consisting of a high-grade fever and an association with underlying diseases and gastrointestinal symptoms. Of note, 3 agammaglobulinemic patients presented with bacteremia and extraintestinal infections and had multiple relapses. Based on the findings of our 9 cases and previous reports, the affected patients were divided into two groups according to clinical syndrome and therapeutic intervention. One group consisted of previously healthy children or young adults showing bacteremia. Most of them had enterocolitis complications but had a good prognosis. The other group consisted of patients with underlying diseases or elderly patients who presented with bacteremia alone or bacteremia with extraintestinal infections. The latter group, especially among those with humoral immunodeficiency, should be parentally treated with antimicrobial agents and requires careful monitoring for relapse. This is the largest case series study to examine invasive C. jejuni/coli infections in Japan,

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Campylobacter Infections; Campylobacter jejuni; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Japan; Male; Microbial Sensitivity Tests; Middle Aged; Young Adult

Infections caused by multidrug-resistant Acinetobacter baumannii have become a therapeutic challenge for clinicians worldwide. Although colistin and tigecycline have been successful in treating patients with these infections, these agents are not available on a worldwide basis. We describe four critically ill patients in Taiwan who were diagnosed with multidrug-resistant Acinetobacter baumannii bacteremia. All bacterial isolates from these patients were resistant to commonly available antibiotics, including carbapenems and sulbactam; however, combination therapy with a carbapenem and sulbactam led to favorable clinical outcomes in all four patients. We also conducted an in vitro study using isolates from these patients that showed that this drug combination had a synergistic effect with enhanced antibacterial activity against the isolates. Thus, a carbapenem-sulbactam combination may be a therapeutic alternative for multidrug-resistant Acinetobacter baumannii bacteremia in countries where colistin and tigecycline are not available for clinical use.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Cilastatin; Cilastatin, Imipenem Drug Combination; Critical Illness; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Meropenem; Microbial Sensitivity Tests; Sulbactam; Taiwan; Thienamycins

To evaluate epidemiology, resistance, and treatment outcomes of Acinetobacter baumannii bacteremia treated with imipenem-cilastatin or ampicillin-sulbactam for 72 hours or longer.. Retrospective analysis.. University teaching hospital.. Forty-eight patients with A. baumannii bacteremia.. Evaluation of susceptibility and clinical data from 48 patients treated with either ampicillin-sulbactam or imipenem-cilastatin from 1987-1999.. Comparing ampicillin-sulbactam and imipenem-cilastatin, there were no differences between days of bacteremia (4 vs 2 days, p=0.05), days to resolution of temperature or white blood cell count, success or failure during or at end of treatment, or intensive care unit total or antibiotic-related length of stay (13 vs 10 days, p=0.05). Patients treated with ampicillin-sulbactam had significantly decreased antibiotic treatment costs (1500 dollars vs 500 dollars, p=0.004).. Ampicillin-sulbactam is at least as effective as imipenem-cilastatin based on clinical response at days 2, 7, and end of treatment and is a cost-effective alternative for treatment of A. baumannii infections.

Topics: Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Ampicillin; Bacteremia; Chi-Square Distribution; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Middle Aged; Retrospective Studies; Statistics, Nonparametric; Sulbactam; Treatment Outcome

Topics: Adult; Ampicillin Resistance; Bacteremia; Cefotaxime; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Administration Schedule; Drug Combinations; Drug Resistance, Multiple; Drug Therapy, Combination; Female; Follow-Up Studies; Gentamicins; Humans; Imipenem; Infant, Newborn; Injections, Intravenous; Male; Pregnancy; Pregnancy Complications, Infectious; Proteus; Proteus Infections; Puerperal Infection; Treatment Outcome

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Humans; Imipenem; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Neutropenia; Treatment Outcome