Laura Czekster Antochevis

Polymyxin B in Combination with Antimicrobials Lacking In Vitro Activity versus Polymyxin B in Monotherapy in Critically Ill Patients with Acinetobacter baumannii or Pseudomonas aeruginosa Infections

ABSTRACT There is no clinical evidence supporting the use of polymyxin B in combination with another antimicrobial for infections caused by extensively drug-resistant Acinetobacter baumannii or Pseudomonas aeruginosa isolates. We developed a cohort study of patients in two intensive care units from teaching hospitals to evaluate treatment with intravenous polymyxin B for ≥48 h for severe A. baumannii or P. aeruginosa infections. Covariates potentially associated with 30-day mortality were evaluated in a Cox proportional hazards model. A total of 101 patients were included; 33 (32.7%) were treated with polymyxin B in combination with an antimicrobial lacking in vitro activity and 68 (67.3%) with polymyxin B in monotherapy. The overall 30-day mortality was 59.4% (60 patients), comprising 42.4% (14 of 33) and 67.6% (46 of 68) in combination and monotherapy groups, respectively (P = 0.03). The mortality rates were 18.5/1,000 patient days and 36.4/1,000 patient days in the combination and monotherapy groups, respectively (P = 0.02). Combination therapy was independently associated with lower 30-day mortality (hazard ratio, 0.33; 95% confidence interval, 0.17 to 0.64; P = 0.001). Creatinine clearance of ≥60 ml/min was also a protective factor, while a higher acute physiology and chronic health evaluation (APACHE II) score and polymicrobial infection were associated with increased mortality. The results did not change after adding a propensity score for prescribing combination therapy into the model. The protective effect remained when only combination with β-lactam or carbapenem was considered and in both subgroups of patients: those with A. baumannii infection and those with lower respiratory tract infections. To our knowledge, this is the first clinical study to show a benefit of combination over monotherapy with polymyxin B for severe extensively drug-resistant A. baumannii or P. aeruginosa infections.

Detection of OXA-370, an OXA-48-related class D β-lactamase, in Enterobacter hormaechei from Brazil

Jorge L. M. Sampaio, Vanessa B. Ribeiro, Juliana Coutinho Campos, Franciéli P. Rozales, Cibele M. Magagnin, Diego R. Falci, Renato Cassol F. da Silva, Micheline G. Dalarosa, Daniela I. Luz, Fabiane J. Vieira, Laura C. Antochevis, Afonso Luis Barth, Alexandre P. Zavascki Departamento de Análises Clínicas e Toxicológicas—Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, Brazil; Microbiologia—Fleury Medicina e Saúde, São Paulo, Brazil; Laboratório de Pesquisa em Resistência Bacteriana—LABRESIS, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Programa de PósGraduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Infection Control Service, Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil; Infectious Diseases Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Department of Internal Medicine, Medical School, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

In vitro susceptibility of chromoblastomycosis agents to five antifungal drugs and to the combination of terbinafine and amphotericin B

Chromoblastomycosis is a chronic mycosis that affects the skin and subcutaneous tissues caused by several genera of dematiaceous fungi. There is not a treatment of choice. Thus, tools that help guide clinical practice are fundamental. In this sense, antifungal activity tests in vitro could be useful. However, trials with chromoblastomycosis agents are scarce. The aim of this study was to evaluate both the in vitro susceptibility of 60 chromoblastomycosis agents to five antifungals and the combination of amphotericin B (AMB) and terbinafine (TRB). TRB, itraconazole (ITZ) and ketoconazole (KTZ) were, in this order, the drugs which showed better activity against the chromoblastomycosis agents. The less active drugs were voriconazole (VRZ) and AMB. The more differentiated group was Exophiala spinifera. Cladophialophora carrionii and Fonsecaea spp. are significantly more susceptible to KTZ than Phialophora verrucosa, whereas C. carrionii is significantly more sensitive to VRZ than P. verrucosa and E. spinifera. Assays in this direction allow the knowledge of the susceptibility of the causative agents which may help the management of patients with this disease. This study includes the largest number of these agents and of genera found in the literature.

Emergence of polymyxin B resistance in a polymyxin B-susceptible KPC-producing Klebsiella pneumoniae causing bloodstream infection in a neutropenic patient during polymyxin B therapy

The emergence of resistance to polymyxins in KPC-producing Klebsiella pneumoniae isolates has been a major clinical problem. This study evaluated the molecular mechanisms associated with polymyxin B (PMB) resistance that emerged in a previously PMB-susceptible KPC-2-producing K. pneumoniae during PMB therapy for a bloodstream infection in a neutropenic patient. The first isolate (PMB-susceptible) was obtained while the patient was receiving meropenem and other isolates were recovered from 2 sets of blood cultures in different dates while the patient was receiving PMB therapy (4 of 6 blood cultures bottles yielded isolates with full PMB resistance). The population analysis profile of the first isolate revealed the growth of resistant subpopulations with PFGE profile distinct from the parental isolate but undistinguishable from those obtained in subsequent days under PMB exposure. Resistant subpopulations were obtained from all parental PMB-susceptible and in one PMB-resistant isolate recovered from the patient. The molecular mechanism observed in the hetero-resistant subpopulations (IS1-like in mgrB-promoter region, increased rstB transcription with no mutation and non-identified mechanism) differed from those found in the PMB-resistant isolates, in which no mutation or transcriptional alterations were detected. This study showed that the mechanism of resistance to PMB that emerged during PMB therapy was not related to those observed in subpopulations selected in vitro from PMB-susceptible isolates recovered from the patient. The absence of mutations in the former isolates may be due to adaptive resistance occurred because of sub-optimal PMB levels as well as amikacin and meropenem used in combination.