In Vitro Bactericidal Activity of Trimethoprim-Sulfamethoxazole Alone and in Combination with Colistin against Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates.

Trimethoprim-sulfamethoxazole alone and combined with colistin was tested in vitro against six carbapenem-resistant Acinetobacter baumannii (CRAB) clinical strains. After 24 h, at achievable serum concentrations, trimethoprim-sulfamethoxazole effectively killed all strains, while colistin killed only one strain. Trimethoprim-sulfamethoxazole plus colistin rapidly killed all strains after 6 h and for up to 24 h. Trimethoprim-sulfamethoxazole, one of the few remaining antimicrobials that still has a degree of activity, particularly combined with colistin, might represent an effective therapy for severe CRAB infections.

Acute generalized livedo racemosa caused by Capnocytophaga canimorsus identified by MALDI-TOF MS.

Independent of the size of the dog and the type of injury, serious infections may follow a dog bite and these may result in the abrupt onset of multiorgan failure. Early recognition of the warning signs with regard to the underlying severity of the infection is of the utmost importance. Reticulate skin eruptions constitute a precursory phenomenon.

Breakthrough candidaemia caused by phenotypically susceptible Candida spp. in patients with haematological malignancies does not correlate with established interpretive breakpoints.

In a study of 27,864 patients with haematological malignancies, 40 patients with candidaemia were identified, among whom 21 developed candidaemia while receiving systemic antifungal therapy [breakthrough candidaemia (BTC)]. Demographic, clinical, microbiological and molecular features of these episodes were analysed. Compared with 19 patients with de novo candidaemia, patients with BTC were more likely to have neutropenia (81% vs. 63%), longer median duration of neutropenia (27 days vs. 15 days), hypogammaglobulinaemia (62% vs. 37%) and central venous catheters (CVCs) (86% vs. 68%). The median duration of prior antifungal exposure was 46 days (range 3-108 days). Among the 18 available Candida spp. isolates, 15 (83%) were phenotypically susceptible to the antifungal agent that the patient was receiving. Emergence of resistance was the mechanism leading to BTC in three cases of patients receiving echinocandins. Other possible mechanisms of BTC were (i) elevated (≥2) minimum lethal concentration/minimum inhibitory concentration (MLC/MIC) ratio (reduced ability for a fungicidal agent to kill a fungal pathogen) in all patients receiving amphotericin B and (ii) elevated MLC/MIC ratios in all Candida parapsilosis isolates with MICs≤1 µg/mL to echinocandins. DNA sequencing of the hotspot 1 region of the fks1 and fks2 genes in seven different isolates of C. parapsilosis group demonstrated P660A in Fks1 but no polymorphisms in fks2. In conclusion, mechanisms for BTC in the setting of prolonged neutropenia may be host-based (hypogammaglobulinaemia and CVC) and pathogen-based. CLSI interpretive breakpoints do not reliably predict BTC in patients with haematological malignancies and warrant further investigation.

Carbapenemase-producing Klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotic combination schemes and the role of carbapenems.

Carbapenemase-producing Klebsiella pneumoniae strains (CP-Kps) are currently among the most important nosocomial pathogens. An observational study was conducted during 2009 to 2010 in two hospitals located in a high-prevalence area (Athens, Greece). The aims were (i) to evaluate the clinical outcome of patients with CP-Kp bloodstream infections (BSIs), (ii) to identify predictors of mortality, and (iii) to evaluate the various antibiotic schemes employed. A total of 205 patients with CP-Kp BSIs were identified: 163 (79.5%) were infected with KPC or KPC and VIM, and 42 were infected with VIM producers. For definitive treatment, 103 patients received combination therapy (two or more active drugs), 72 received monotherapy (one active drug), and 12 received therapy with no active drug. The remaining 18 patients died within 48 h after the onset of bacteremia. The all-cause 28-day mortality was 40%. A significantly higher mortality rate was observed in patients treated with monotherapy than in those treated with combination therapy (44.4% versus 27.2%; P=0.018). The lowest mortality rate (19.3%) was observed in patients treated with carbapenem-containing combinations. In the Cox proportion hazards model, ultimately fatal disease (hazards ratio [HR], 3.25; 95% confidence interval [CI], 1.51 to 7.03; P=0.003), the presence of rapidly fatal underlying diseases (HR, 4.20; 95% CI, 2.19 to 8.08; P<0.001), and septic shock (HR, 2.15; 95% CI, 1.16 to 3.96; P=0.015) were independent predictors of death. Combination therapy was strongly associated with survival (HR of death for monotherapy versus combination, 2.08; 95% CI, 1.23 to 3.51; P=0.006), mostly due to the effectiveness of the carbapenem-containing regimens.