colistin and Intraabdominal-Infections

Ceftolozane-tazobactam is currently the most active antipseudomonal agent, including multidrug-resistant extensively drug-resistant strains. Tazobactam provides additional activity against many extended-spectrum beta-lactamases Enterobacterales. Ceftolozane-tazobactam is formally approved for complicated urinary tract infection, complicated intra-abdominal infection, and hospital-acquired and ventilator-associated bacterial pneumonia. The clinical and microbiological success is over 70-80% in many series. However, resistant mutants to ceftolozane-tazobactam have been already described. Combination therapies with colistin or meropenem could be among the strategies to avoid the resistance emergence.

Topics: Anti-Bacterial Agents; Cephalosporins; Colistin; Humans; Intraabdominal Infections; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Tazobactam

In this study, we aimed to assess the geographic distribution and molecular characteristics of β-lactamases among Enterobacterales isolates causing intra-abdominal infections (IAIs) from 2015 to 2018 in the Asia-Pacific region.. Isolates were investigated for extended-spectrum β-lactamases (ESBLs), AmpC β-lactamases, and carbapenemases using multiplex PCR assays and full-gene DNA sequencing.. A total of 832 Enterobacterales isolates from 8 different countries with β-lactamase genes were analysed. Plasmid-mediated ESBLs and AmpC β-lactamases were encoded in 598 (71.9 %) and 314 (37.7 %) isolates, respectively. In 710 (85.3 %) carbapenemase-negative isolates, positivity for both AmpC β-lactamases and ESBLs was identified in 51 (8.5 %) Escherichia coli and 24 (3.4 %) Klebsiella pneumoniae isolates. The most prevalent countries were Taiwan and Vietnam, and the co-occurrence of CMY/CTX-M in E. coli and DHA-1/ESBLs in K. pneumoniae was predominant. All isolates showed high susceptibility to colistin, but susceptibility to carbapenems varied among different resistance mechanism combinations. Among 122 (14.7 %) isolates encoding carbapenemase, NDM (n = 67, including 64.2 % NDM-1) was the most common, followed by the OXA-48-type (n = 49), KPC (n = 24) and IMP (n = 4). The most prevalent country was Thailand (n = 44), followed by Vietnam (n = 35) and the Philippines (n = 21). Twenty-two isolates were found to encode multiple carbapenemases, 16 of which were collected from Thailand and harbored NDM-1, OXA-232 and CTX-M-15. Despite high susceptibility to amikacin, susceptibility to colistin was only 56 %.. The emergence of carbapenem-non-susceptible AmpC/ESBL co-occurring Enterobacterales and colistin non-susceptible carbapenemases co-occurring K. pneumoniae highlights potential therapeutic challenges in the Asia-Pacific region.

Topics: Anti-Bacterial Agents; Asia, Eastern; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Drug Resistance, Bacterial; Escherichia coli; Humans; Intraabdominal Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

Post-surgical intra-abdominal infections (IAIs) due to carbapenem-resistant Acinetobacter baumannii (CRAB) are difficult to treat due to suboptimal peritoneal penetrations of several antimicrobial agents. Tigecycline has favorable outcomes of treating IAIs due to multidrug-resistant organisms but occurrence of breakthrough bacteremia has been observed because this agent has low serum level. Colistin has in vitro activity against CRAB but data on treatment of IAIs is limited due to poor peritoneal penetration. The purpose of this retrospective study is to explore the outcomes of adjunctive intravenous (IV) colistin to IV tigecycline in the treatment of IAIs caused by CRAB. Of 28 patients with non-bacteremic post-surgical IAIs due to CRAB, 14 patients received IV tigecycline alone and 14 patients received IV tigecycline with IV colistin. The 14-day, 30-day, in-hospital mortality rates, the rate of breakthrough bacteremia and the rate of bacterial eradication were not significantly different. The adjunctive therapy of IV colistin was associated with significantly higher rates of renal complications (10/14) than those receiving IV tigecycline alone (3/14) (P value = 0.023). In addition, the patients receiving adjunctive IV colistin had significantly more unfavorable non-clinical outcomes including longer length of hospital stay (P value = 0.049) and higher antimicrobial cost (P value = 0.008) and non-antimicrobial costs (P value = 0.037). In this study, adjunctive IV colistin to conventional IV tigecycline in the treatment of non-bacteremic post-surgical IAIs caused by CRAB did not yield clinical benefit but caused higher renal complication and unfavorable non-clinical outcomes.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Adult; Carbapenems; Colistin; Drug Resistance, Microbial; Female; Humans; Intraabdominal Infections; Male; Middle Aged; Postoperative Complications; Renal Insufficiency; Retrospective Studies; Tigecycline

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) infections represent a major therapeutic problem and combination therapy may be the chemotherapeutic option.. Bioluminescent CRPA was developed through sequential subcultures in subinhibitory concentrations of meropenem from an engineered strain of bioluminescent PA Xen5. Then CRPA was injected intraperitoneally to establish an intraperitoneal murine infection model. Treatments of colistin alone or combined with rifampicin or meropenem were started 1 h after infection. In vivo bioluminescence imaging was applied dynamically at 0 h, and 2 and 5 h after treatment. Ex vivo bacterial counts from liver, kidney, spleen, lung and blood samples were also determined 5 h after treatment.. In vivo imaging showed that both low- and high-dose colistin combined with rifampicin resulted in a significant decrease in bioluminescence signals compared with monotherapy of colistin or rifampicin alone, whereas colistin and meropenem combination therapy did not show a greater bactericidal effect compared with monotherapy. Ex vivo bacterial count results also confirmed that combination of both low- and high-dose colistin with rifampicin resulted in significantly reduced colony counts from five kinds of tissue samples. However, only combination of high-dose colistin + meropenem resulted in reduced colony counts merely in lung and blood samples.. Compared with single drugs, colistin and rifampicin combination therapy could exert synergistic effects, which might provide a better alternative when treating CRPA infections in clinical practice. Combination of colistin and meropenem should be considered with caution because it barely shows any synergism in the present in vivo model.

Topics: Animal Structures; Animals; Anti-Bacterial Agents; Bacterial Load; beta-Lactam Resistance; Colistin; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Female; Intraabdominal Infections; Luminescent Measurements; Meropenem; Mice, Inbred BALB C; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Staining and Labeling; Treatment Outcome

Nephrotoxicity is the main adverse effect of colistin and polymyxin B (PMB). It is not clear whether these two antibiotics are associated with different nephrotoxicity rates. We compared the incidences of renal failure (RF) in patients treated with colistimethate sodium (CMS) or PMB for ≥48 h. A multicenter prospective cohort study was performed that included patients aged ≥18 years. The primary outcome was renal failure (RF) according to Risk, Injury, Failure, Loss, and End-stage renal disease (RIFLE) criteria. Multivariate analysis with a Cox regression model was performed. A total of 491 patients were included: 81 in the CMS group and 410 in the PMB group. The mean daily doses in milligrams per kilogram of body weight were 4.2 ± 1.3 and 2.4 ± 0.73 of colistin base activity and PMB, respectively. The overall incidence of RF was 16.9% (83 patients): 38.3% and 12.7% in the CMS and PMB groups, respectively (P< 0.001). In multivariate analysis, CMS therapy was an independent risk factor for RF (hazard ratio, 3.35; 95% confidence interval, 2.05 to 5.48;P< 0.001) along with intensive care unit admission, higher weight, older age, and bloodstream and intraabdominal infections. CMS was also independently associated with a higher risk of RF in various subgroup analyses. The incidence of RF was higher in the CMS group regardless of the patient baseline creatinine clearance. The development of RF during therapy was not associated with 30-day mortality in multivariate analysis. CMS was associated with significantly higher rates of RF than those of PMB. Further studies are required to confirm our findings in other patient populations.

Topics: Acute Kidney Injury; Adult; Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Body Weight; Colistin; Drug Administration Schedule; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Intensive Care Units; Intraabdominal Infections; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Polymyxin B; Prospective Studies; Respiratory Tract Infections; Risk Factors; Survival Analysis

Topics: Child; Colistin; Enteritis; Escherichia coli Infections; Humans; Infant; Intraabdominal Infections; Salmonella Infections