Silvana Superti

Pharmacokinetics of Intravenous Polymyxin B in Critically Ill Patients

BACKGROUND Although not much pharmacokinetic knowledge is available, polymyxin B is increasingly used for treatment of infections caused by gram-negative bacteria that are resistant to all other antibiotics. METHODS This study involved 8 patients who received intensive care after intravenous administration of a 60-min infusion of polymyxin B at currently recommended doses. Blood and urine samples were collected, and plasma protein binding of polymyxin B was determined. Concentrations of polymyxin B in plasma and urine samples were measured by a specific high-performance liquid chromatographic method. RESULTS Polymyxin B was well tolerated. The peak plasma concentrations at the end of the infusion varied from 2.38 to 13.9 mg/L. For 4 patients from whom it was possible to collect urine samples over a dosing interval, only 0.04%-0.86% of the dose was recovered in the urine in unchanged form. Plasma protein binding of polymyxin B was higher in samples from patients (range, 78.5%-92.4%) than in plasma samples from healthy human subjects (mean +/- standard deviation, 55.9% +/- 4.7%). Unbound plasma concentrations of polymyxin B were in the vicinity of or lower than the minimum inhibitory concentration of the pathogen. CONCLUSION To our knowledge, this is the first study to report plasma concentrations over time and urinary recovery of polymyxin B in critically ill patients after intravenous administration. Polymyxin B is eliminated mainly by nonrenal pathways, and the total body clearance appears to be relatively insensitive to renal function. Additional investigations are required to assess the appropriateness of currently recommended doses of this drug for the treatment of severe infections in critically ill persons.

Risk factors for and mortality of extended-spectrum-β-lactamase-producing Klebsiella pneumoniae and Escherichia coli nosocomial bloodstream infections.

A case-control study, involving patients with positive blood cultures for Klebsiella pneumoniae (KP) or Escherichia coli (EC) EC and controls with positive blood cultures for non-ESBL-KP or EC, was performed to assess risk factors for extended-spectrum-beta-lactamase (ESBL) production from nosocomial bloodstream infections (BSIs). Mortality among patients with BSIs was also assessed. The study included 145 patients (81, 59.5% with K. pneumoniae and 64, 44.1% with E. coli BSI); 51 (35.2%) isolates were ESBL producers and 94 (64.8%) nonproducers. Forty-five (55.6%) K. pneumoniae isolates were ESBL producers, while only six (9.4%) E. coli isolates produced the enzyme. Multivariate analysis showed that recent exposure to piperacillin-tazobactam (adjusted Odds Ratio [aOR] 6.2; 95%CI 1.1-34.7) was a risk factor for ESBL BSI. K. pneumoniae was significantly more likely to be an ESBL-producing isolate than E. coli (aOR 6.7; 95%CI 2.3-20.2). No cephalosporin class was independently associated with ESBLs BSI; however, in a secondary model considering all oxymino-cephalosporins as a single variable, a significant association was demonstrated (aOR 3.7; 95%CI 1.3-10.8). Overall 60-day mortality was significantly higher among ESBL-producing organisms. The finding that piperacillin-tazobactam use is a risk factor for ESBL-production in KP or EC BSIs requires attention, since this drug can be recommended to limit the use of third-generation cephalosporins.

Clinical and molecular epidemiology of methicillin-resistant Staphylococcus aureus carrying SCCmecIV in a university hospital in Porto Alegre, Brazil

We evaluated clinical outcomes and molecular epidemiology of methicillin-resistant Staphylococcus aureus carrying SCCmecIV recovered from patients who attended at a teaching hospital from Porto Alegre, Brazil. All Panton-Valentine leukocidin (PVL)-producer isolates belonged to clonal complex (CC) 30 (11 isolates, related to Oceania Southwest Pacific clone [OSPC]), and the PVL-negative isolates were typed as CC5 (2 isolates, related to the pediatric clone). Five patients had health care-associated infections (HCAIs) with hospital-onset, 5 HCAIs with community-onset, and 3 community-acquired infections without risks. A high overall mortality (30.8%) was found. This study show that OSPC isolates are not only causing community-associated infections but are also involved in HCAI in our country.

Automated systems in the identification and determination of methicillin resistance among coagulase negative staphylococci

Coagulase-negative staphylococci (CoNS) are an important cause of nosocomial bacteremia, specially in patients with indwelling devices or those submitted to invasive medical procedures. The identification of species and the accurate and rapid detection of methicillin resistance are directly dependent on the quality of the identification and susceptibility tests used, either manual or automated. The objective of this study was to evaluate the accuracy of two automated systems--MicroScan and Vitek--in the identification of CoNS species and determination of susceptibility to methicillin, considering as gold standard the biochemical tests and the characterization of the mecA gene by polymerase chain reaction, respectively. MicroScan presented better results in the identification of CoNS species (accuracy of 96.8 vs 78.8%, respectively); isolates from the following species had no precise identification: Staphylococcus haemolyticus, S. simulans, and S. capitis. Both systems were similar in the characterization of methicillin resistance. The higher discrepancies for gene mec detection were observed among species other than S. epidermidis (S. hominis, S. saprophyticus, S. sciuri, S. haemolyticus, S. warneri, S. cohnii), and those with borderline MICs.

First case report of Neisseria lactamica causing cavitary lung disease in an adult organ transplant recipient.

ABSTRACT We describe a case of an adult organ recipient patient with a pulmonary cavitary lesion due to Neisseria lactamica, a harmless commensal organism that rarely causes human infection. To our knowledge, this is the first report of pulmonary disease caused by this organism and the second case of N. lactamica infection in an adult patient.

Corynebacterium striatum infecting a malignant cutaneous lesion: the emergence of an opportunistic pathogen

We described a case of a 27-year old male patient with skin and soft tissue infection of a neoplastic lesion caused by Corynebacterium striatum, an organism which has been rarely described as a human pathogen. Identification was confirmed by DNA sequencing. Successful treatment with penicillin was achieved. The role of the C. striatum as an emerging opportunistic pathogen is discussed.

Agar diffusion, agar dilution, Etest®, and agar screening test in the detection of methicillin resistance in staphylococci

Methicillin resistant Staphylococcus is an important worldwide problem. Resistance is verified in strains harboring the mecA gene and laboratory methods used to detect resistance are object of constant investigation. In the present study, 99 clinical isolates of staphylococci (41 S. aureus, 33 S. epidermidis, 12 S. saprophyticus and 13 members of other species) were submitted to different phenotypic methods and conditions. Detection of the mecA gene by PCR was used as the reference method and detected 14/41, 10/33, and 10/25 isolates of S. aureus, S. epidermidis and other species, respectively. Results showed that, for S. aureus and S. epidermidis, agar diffusion, agar dilution, and the E test incubated during 24h at 35 degrees C correctly discriminated mecA positive from mecA negative isolates. For other species, all methods and conditions presented low specificity (ranging from 20% to 66.7%) and, particularly S. saprophyticus, may need molecular methods to correctly assess methicillin resistance.

Risk factors for 30-day mortality in patients with carbapenem-resistant Acinetobacter baumannii during an outbreak in an intensive care unit

This study assessed risk factors for 30-day mortality in 66 patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infection or colonization during an outbreak in an intensive-care unit. Clinical and demographic characteristics were evaluated. The overall 30-day mortality was 47·0%. In the multivariate Cox regression model, septic shock [adjusted hazard ratio (aHR) 5·01, 95% confidence interval (CI) 2·32-10·01] and APACHE II score at onset of infection (aHR 1·11, 95% CI 1·04-1·18) were significantly associated with 30-day mortality. Administration of appropriate therapy was a protective factor, but it was not statistically significant (aHR 0·48, 95% CI 0·21-1·12). A sample of isolates tested (n=27) carried the blaOXA-23 gene. Severity of baseline condition and severity of infection presentation were major risk factors for mortality during the outbreak. Patients who received appropriate therapy tended to have lower mortality rates, although therapy was started late and dosage was suboptimal in most cases.

Stable Polymyxin B Susceptibility to Pseudomonas aeruginosa and Acinetobacter spp. despite Persistent Recovery of These Organisms from Respiratory Secretions of Patients with Ventilator-Associated Pneumonia Treated with This Drug

In a recent article, Lee et al. ([4][1]) reported the occurrence of an increase in MICs for polymyxin B during therapy in 3 of 16 patients treated with this drug for carbapenem-resistant Klebsiella pneumoniae infections. This report is very important, since polymyxins, polymyxin B and colistin, are

Avaliação de um sistema automatizado na identificação de espécies de Enterococcus

O uso de metodos automatizados tem frequentemente levado a falhas na identificacao do genero Enterococcus em laboratorios de microbiologia clinica. Neste estudo foi avaliada a utilizacao de um sistema automatizado Vitek (bioMerieux) em dois laboratorios de microbiologia clinica para identificacao de diferentes especies de enterococos. Os resultados foram comparados com os testes fisiologicos convencionais. As amostras (80) foram inoculadas em testes bioquimicos convencionais e no cartao Vitek GPI. No geral, a concordância entre os dois metodos foi de 83,7% (67/80). Entre as amostras de E. faecalis, o sistema Vitek identificou corretamente 35/40 (87,5%) e entre os E. faecium, a concordância foi 12/14 (85,7%). Em 20/26 amostras (76,9%) pertencentes a especies nao-E. faecalis e nao-E. faecium, o sistema chegou a identificacao correta. Os resultados do presente estudo mostram que o sistema Vitek necessita de melhorias para a identificacao de enterococos, especialmente diante de especies menos frequentes.