Antimicrobial agents and chemotherapy
-
Antimicrob. Agents Chemother. · Oct 2014
Antibiotic pressure is a major risk factor for rectal colonization by multidrug-resistant Pseudomonas aeruginosa in critically ill patients.
The intestinal reservoir is central to the epidemiology of Pseudomonas aeruginosa, but the dynamics of intestinal colonization by different phenotypes have been poorly described. To determine the impact of antimicrobial exposure on intestinal colonization by multidrug-resistant (MDR) and extensively drug-resistant (XDR) P. aeruginosa, we screened intensive care unit (ICU) patients for rectal colonization on admission and at weekly intervals. During an 18-month study period, 414 ICU patients were enrolled, of whom 179 (43%) were colonized; 112 (63%) of these were identified at ICU admission and 67 (37%) during their ICU stay. ⋯ The Cox regression analysis identified MDR P. aeruginosa acquisition as associated with the underlying disease severity (adjusted hazard ratio [aHR], 1.97; 95% confidence interval [CI], 1.22 to 3.18; P = 0.006) and prior use of fluoroquinolones (aHR, 1.02; 95% CI, 1.00 to 1.04; P = 0.039), group 2 carbapenems (aHR, 1.03; 95% CI, 1.00 to 1.07; P = 0.041), and ertapenem (aHR, 1.08; 95% CI, 1.02 to 1.14; P = 0.004). The epidemiology of MDR P. aeruginosa is complex, and different clusters may coexist. Interestingly, ertapenem was found to be associated with the emergence of MDR isolates.
-
Antimicrob. Agents Chemother. · Oct 2014
In vivo effect of quaternized chitosan-loaded polymethylmethacrylate bone cement on methicillin-resistant Staphylococcus epidermidis infection of the tibial metaphysis in a rabbit model.
Infection of open tibial fractures with contamination remains a challenge for orthopedic surgeons. Local use of antibiotic-impregnated polymethylmethacrylate (PMMA) beads and blocks is a widely used procedure to reduce the risk of infection. However, the development of antibiotic-resistant organisms make the management of infection more difficult. ⋯ The radiographic scores and gross bone pathological and histopathological scores were significantly lower in the PMMA-H group than in the PMMA, PMMA-G, and PMMA-C groups (P < 0.05). Explant cultures also indicated significantly less bacterial growth in the PMMA-H group than in the PMMA, PMMA-G, and PMMA-C groups (P < 0.01). We concluded that PMMA-H bone cement can inhibit the development of bone infections in this animal model inoculated with antibiotic-resistant bacteria, thereby demonstrating its potential application for treatment of local infections in open fractures.
-
Antimicrob. Agents Chemother. · Sep 2014
Prevention of transmission of multidrug-resistant organisms during catheter exchange using antimicrobial catheters.
Exchanging a central venous catheter (CVC) over a guide wire for a fresh uncoated CVC in the presence of bacteremia can result in cross-infection of the newly exchanged CVC. A recent retrospective clinical study showed that exchanging a catheter over a guide wire in the presence of bacteremia using an antimicrobial minocycline-rifampin (M/R) catheter may improve outcomes. To expand on this, we developed an in vitro cross-contamination model of exchange to evaluate the efficacy of different antimicrobial CVCs in preventing cross-contamination of multidrug-resistant organisms during exchange. ⋯ Exchange with CHX-M/R CVCs completely prevented cross-contamination by MRSA, P. aeruginosa, and C. albicans biofilms (P<0.0001). Furthermore, CHX-M/R CVCs were superior to M/R CVCs against P. aeruginosa and C. albicans (P=0.003) and were superior to CHX/SS CVCs against MRSA and P. aeruginosa (P=0.01). In conclusion, exchange with the novel CHX-M/R CVC was the only exchange effective in completely and concurrently preventing cross-contamination from bacteria and Candida.
-
Antimicrob. Agents Chemother. · Sep 2014
Randomized Controlled Trial Multicenter Study Comparative StudyMulticenter, double-blind, randomized, phase II trial to assess the safety and efficacy of ceftolozane-tazobactam plus metronidazole compared with meropenem in adult patients with complicated intra-abdominal infections.
Ceftolozane-tazobactam (TOL-TAZ) is a novel antibacterial with activity against Pseudomonas aeruginosa and other common Gram-negative pathogens, including extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, that are associated with complicated intra-abdominal infections (cIAIs). This prospective, double-blind, randomized, multicenter, phase II trial assessed patient clinical and microbiological responses to and the safety of TOL-TAZ plus metronidazole compared with those of meropenem. Hospitalized adults with cIAIs that required surgical intervention were randomized (2:1) to receive intravenous (i.v.) TOL-TAZ (1.5 g [containing 1,000 mg TOL and 500 mg TAZ] every 8 h [q8h]) with or without i.v. metronidazole (500 mg q8h) or i.v. meropenem (1 g q8h) for 4 to 7 days. ⋯ The adverse event rates were similar in the groups (50.0% with TOL-TAZ and 48.8% with meropenem). TOL-TAZ in combination with metronidazole was well tolerated and resulted in clinical and microbiological success rates supportive of further clinical development in patients with cIAIs. (This study has been registered at ClinicalTrials.gov under registration no. NCT01147640.).
-
Antimicrob. Agents Chemother. · Sep 2014
Evaluation of the pharmacokinetics and pharmacodynamics of liposomal amikacin for inhalation in cystic fibrosis patients with chronic pseudomonal infections using data from two phase 2 clinical studies.
The pharmacokinetic-pharmacodynamic (PK-PD) relationships between serum exposure measures of liposomal amikacin for inhalation (LAI) and the change in pulmonary function test (PFT) measures and number of CFU from baseline were evaluated in cystic fibrosis (CF) patients chronically infected with Pseudomonas aeruginosa. A dose of 70, 140, 280, or 560 mg of LAI or placebo was administered to CF patients once daily for 28 days. PFTs and sputum samples for microbiology were assessed on days 7, 14, 21, 28, 35 (for log10 CFU), and 56 (for PFTs). ⋯ The increases in the relative change in FEV1 and FEV1% predicted of 11% and 9.9%, respectively, and a 1.23-log10 CFU reduction per 560 mg of LAI estimated on day 7 were comparable to the observed increases of 10.7% and 10.3%, respectively, and a 1.24-log10 CFU reduction on the same day. The model-estimated PFT effects were predicted to be sustained to day 28. An additional 0.451-log10 CFU reduction (P=0.022) was estimated on day 14 relative to day 7, with a persistence of effect predicted to day 35.