Guilherme Henrique Campos Furtado

In Vivo Efficacy of a Human-Simulated Regimen of Ceftaroline Combined with NXL104 against Extended-Spectrum-β-Lactamase (ESBL)-Producing and Non-ESBL-Producing Enterobacteriaceae

ABSTRACT Ceftaroline exhibits in vitro activity against extended-spectrum β-lactamase (ESBL)-, AmpC-, and KPC-producing Enterobacteriaceae when combined with the novel β-lactamase inhibitor NXL104. The purpose of this study was to evaluate the efficacy of a human-simulated regimen of ceftaroline plus NXL104 against Enterobacteriaceae in a murine thigh infection model. IMPORTANCE Twelve Enterobacteriaceae isolates were tested with neutropenic ICR mice. Seven of these isolates were also tested with immunocompetent mice. Doses were given to simulate human free-drug exposures of ceftaroline (600 mg) plus NXL104 (600 mg) every 8 h over 24 h by targeting the percentage of time that free drug concentrations remain above the MIC, ƒT>MIC. The change in log10 CFU/ml compared with 0 h controls was observed after 24 h. Human-simulated exposures were achieved against all isolates (MICs of ≤0.015 to 1 μg/ml) in both the neutropenic and the immunocompetent host models, which was equivalent to a ƒT>MIC of 100%. A 0.5 to ≥2 log CFU reduction was observed in the neutropenic thigh infection model. Furthermore, significantly greater reductions in bacterial density were observed for five of seven isolates studied in an immunocompetent model than in the neutropenic-host model. Regardless of immune status, ceftaroline (600 mg) combined with NXL104 (600 mg) every 8 h provided predictable efficacy against ESBL-, non-ESBL-, and KPC-producing isolates with an MIC of ≤1 μg/ml and could be useful in combating the growing threat of resistant Enterobacteriaceae.

Imipenem-resistant Pseudomonas aeruginosa infection at a medical-surgical intensive care unit: Risk factors and mortality

OBJECTIVES The aim of this study was to evaluate the risk factors and attributable mortality associated with imipenem-resistant Pseudomonas aeruginosa (IRPA) infections in a medical-surgical intensive care unit (ICU). METHODS A retrospective case-control study was carried out at a 16-bed medical-surgical ICU in a 780-bed, university-affiliated hospital. All patients admitted from January 1, 2003, to December 31, 2004, who had nosocomial infection caused by IRPA, were included in the study. RESULTS Imipenem-resistant P. aeruginosa was recovered from 63 patients during the study period. One hundred eighty-two controls were matched with cases by period of admission, age, and time at risk. Urinary tract (34.9%) and respiratory tract (22.2%) were the main sources of IRPA isolation. In multivariate analysis, a previous stay in the ICU (odds ratio, 3.54; 95% confidence interval [CI], 1.29-9.73; P = .03) was the only independent risk factor for IRPA infection. The in-hospital mortality rate among case patients was 49% (31 of 63) compared with 33% (61 of 182) for control patients (odds ratio, 1.92; 95% CI, 1.07-3.44; P = .02). Thus, we had an attributable mortality of 16% (95% CI, 9.74%-22.3%; P = .03). CONCLUSIONS Our study suggests that IRPA infections are strongly related to previous ICU stay, and that IRPA infections significantly increase mortality in those critical patients.

Incidência de Enterococcus resistente à vancomicina em hospital universitário no Brasil

OBJETIVO: O enterococo resistente a vancomicina e atualmente um dos principais microorganismos implicados em infeccoes nosocomiais. Assim, realizou-se estudo com o objetivo de avaliar sua epidemiologia em um hospital terciario de ensino. METODOS: Trata-se de um estudo epidemiologico retrospectivo, realizado de 2000 a 2002, que analisou amostras de culturas clinicas positivas para enterococo resistente a vancomicina (VRE) em um hospital universitario com 660 leitos. Procurou-se definir sua incidencia e os principais sitios e unidades de isolamento. Foi verificada a significância entre as variaveis nos tres anos de estudo, sendo considerado como significante p<0,05. RESULTADOS: Houve aumento progressivo na resistencia a vancomicina nas culturas clinicas positivas para Enterococcus spp. nos tres anos de estudo. Em 2000, 9,5% das amostras eram resistentes a vancomicina, com aumento para 14,7% em 2001 e 15,8% em 2002. As unidades com maior numero de isolados foram respectivamente: pronto-socorro (19,5%) e UTI geral (15%); os sitios mais isolados foram: urina (36%) e sangue (20%). CONCLUSOES: Com o aumento progressivo na incidencia de resistencia a vancomicina e da taxa de VRE, concluiu-se ser necessarias medidas de controle mais efetivas para deter a disseminacao do VRE.

Historical trends in the epidemiology of candidaemia: analysis of an 11-year period in a tertiary care hospital in Brazil

Candida species are an important cause of bloodstream infections (BSI). To evaluate the epidemiological, clinical and microbiological aspects of two cohorts {1994-1999 [period 1 (P1) ]; 2000-2004 [period 2 (P2) ]} of candidaemic patients, we performed a retrospective analysis from a laboratory-based survey. A total of 388 candidaemias were identified, with an incidence of 0.20/1,000 patient-days and a significant increase in P2 vs. P1 (0.25 vs. 0.15, p = 0.04). Cancer and prior antibiotic use were frequent and Candida albicans was the most prevalent species found (42.4%). Resistance to fluconazole was found in 2.47% of the strains. No differences were observed in the species distribution of Candida during the study periods. In the P2 cohort, there were higher prevalence of elderly individuals, cardiac, pulmonary and liver diseases, renal failure, central venous catheters and antibiotic therapy. In P1, there were higher prevalence of neurological diseases and chemotherapy. The crude mortality was 55.4%. In conclusion, our incidence rates remained high. Furthermore, the distribution pattern of Candida species and the fluconazole resistance profile remained unchanged. Moreover, we found a clear trend of higher prevalence of candidaemia among the elderly and among patients with comorbidities. Finally, it is necessary to discuss strategies for the prevention and control of Candida BSI in Brazil.

Overview perspective of bacterial resistance

The rapidly escalating prevalence of antimicrobial resistance is a global concern. This reduced susceptibility to currently available antimicrobial agents coupled with the progressive shortage of newly approved compounds is a worrisome situation. Major problems are encountered for a growing number of Gram-positive (i.e., Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus spp.) and Gram-negative pathogens (i.e., Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae). We provide an overview of bacterial resistance focusing on the most common pathogens responsible for infection in both the community and healthcare settings. In addition, several strategies to curb antimicrobial resistance are also discussed. It is increasingly evident that without the introduction of novel antimicrobial agents, a return to the clinical outcomes associated with the pre-antibiotic era are inevitable.

Prevalence and factors associated with rectal vancomycin-resistant enterococci colonization in two intensive care units in São Paulo, Brazil

Vancomycin-resistant enterococci (VRE) are important pathogens causing nosocomial infections, and there is reason for concern about their resistance and great ability to spread in hospital environments, especially intensive-care units (ICU). To determine the prevalence of rectal colonization by VRE, and the risk factors associated with their presence, rectal surveillance swabs were taken from patients under treatment in two intensive-care units (one medical and another both medical and surgical) at São Paulo Hospital, over a two-year period. Thirty-three percent of the 147 patients evaluated had VRE. The only significant variable in the logistic regression was the length of stay in the ICU.

Application of control measures for infections caused by multi-resistant gram-negative bacteria in intensive care unit patients

Multi-resistant gram-negative rods are important pathogens in intensive care units (ICU), cause high rates of mortality, and need infection control measures to avoid spread to another patients. This study was undertaken prospectively with all of the patients hospitalized at ICU, Anesthesiology of the Hospital São Paulo, using the ICU component of the National Nosocomial Infection Surveillance System (NNIS) methodology, between March 1, 1997 and June 30, 1998. Hospital infections occurring during the first three months after the establishment of prevention and control measures (3/1/97 to 5/31/97) were compared to those of the last three months (3/1/98 to 5/31/98). In this period, 933 NNIS patients were studied, with 139 during the first period and 211 in the second period. The overall rates of infection by multi-resistant microorganisms in the first and second periods were, respectively, urinary tract infection: 3.28/1000 patients/day; 2.5/1000 patients/day; pneumonia: 2.10/1000 patients/day; 5.0/1000 patients/day; bloodstream infection: 1.09/1000 patients/day; 2.5/1000 patients/day. A comparison between overall infection rates of both periods (Wilcoxon test) showed no statistical significance (p = 0.067). The use of intervention measures effectively decreased the hospital bloodstream infection rate (p < 0.001), which shows that control measures in ICU can contribute to preventing hospital infections.

Assessment of healthcare professionals' adherence to hand hygiene after alcohol-based hand rub introduction at an intensive care unit in São Paulo, Brazil.

We analyzed the impact of introducing an alcohol-based hand gel and an educational program on hand hygiene adherence among healthcare workers in an intensive care unit. Adherence to hand hygiene was significantly higher after the intervention for the night shift work period (P=.001), among nursing assistants (P=.001), among nurses (P=.007) on weekend days (P=.016), and for invasive procedures (P=.012).

Detection of GES-5-producing Klebsiella pneumoniae in Brazil

Sir, The production of carbapenemases or extended-spectrum b-lactamases (ESBLs) and/or AmpC b-lactamases coupled with porin loss are the most common mechanisms of carbapenem resistance in Klebsiella spp. Amino acid substitutions in the active site of GES-type ESBLs may enhance their spectrum of activity against carbapenems. The variants GES-2, -4, -5, -6 and -11 are able to hydrolyse imipenem; GES-5 hydrolyses this agent most efficiently. To date, GES-5-producing Klebsiella pneumoniae has only been identified in Korea. In this report we investigated the mechanisms responsible for carbapenem resistance in a K. pneumoniae subsp. ozaenae from Brazil. KOZ-Ban2 was isolated from a rectal surveillance swab of an elderly patient admitted to a private hospital in São Paulo, Brazil, in 2008. The patient was admitted with the diagnosis of community-acquired pneumonia and was successfully treated with piperacillin/tazobactam and moxifloxacin. Two weeks later, the patient presented a new episode of pneumonia that was empirically treated with meropenem and teicoplanin, with good clinical outcome. After 5 weeks of hospitalization, the patient was admitted to the intensive care unit with septic shock and respiratory failure. Candida sp. was isolated from the bloodstream at the same time that KOZ-Ban2 was recovered from the rectal swab. The patient died 24 h later. KOZ-Ban2 identification was performed by the BD Phoenix Automated Microbiology System. Susceptibility testing was performed by CLSI agar dilution, and showed that KOZ-Ban2 was resistant to all b-lactams including carbapenems, amikacin, gentamicin, nalidixic acid and ciprofloxacin (Table 1). PCR and amplicon sequencing, using previously reported conditions and primers specific for KPC-, MBLand ESBL-encoding genes and the 50 and 30 conserved sequences of integrons, identified the blaGES-5 gene. This gene was harboured in the first position of a class 1 integron, followed by the aacA4, blaOXA-17, dfrA21 and catB3 cassettes, encoding an aminoglycoside acetyltransferase, an extended-spectrum oxacillinase capable of hydrolysing cefotaxime and cefepime better than ceftazidime, a dihydrofolate reductase and a chloramphenicol acetyltransferase, respectively. This new integron, named In91, had a weak Pc version with the sequence 235 TGGACA and 210 TAAGCT and an inactive P2 (GQ139471). The search for plasmid-mediated quinolone resistance determinants yielded negative results. PCR and sequencing of ompK35 and ompK36 genes revealed that the size of the ompK36 amplicon was 650 bp lower than expected. Sequencing showed that 674 bp was missing in KOZ-Ban2 ompK36 (GQ139473). In addition, although the ompK35 amplicon was the expected size, its sequencing revealed one change at position 689, where the codon TGG changed to the stop codon TAG, probably resulting in a deficient porin that lacked the last 130 amino acids (GQ139472). SDS–PAGE of outer membrane protein (OMP) profiles was performed as previously reported, using a carbapenem-susceptible K. pneumoniae for comparison. The carbapenem-susceptible isolate showed three bands near the 36 kDa band of the molecular weight marker, whereas KOZ-Ban2 had a single band, probably corresponding to OmpA (data not shown). These findings suggest that neither OmpK35 nor OmpK36 was expressed in KOZ-Ban2. Mating-out assays were performed using streptomycin-resistant Escherichia coli K12 as the recipient strain, and selection was

The changing epidemiology of Acinetobacter spp. producing OXA carbapenemases causing bloodstream infections in Brazil: a BrasNet report

We evaluated the epidemiology of Acinetobacter spp. recovered from patients diagnosed with bloodstream infections in 9 tertiary hospitals located in all Brazilian geographic regions between April and August 2014. Although OXA-23-producing Acinetobacter baumannii clones were disseminated in most hospitals, it was observed for the first time the spread of OXA-72 among clonally related A. baumannii isolated from distinct hospitals. Interestingly, Acinetobacter pittii was the most frequent species found in a Northern region hospital. Contrasting with the multisusceptible profile displayed by A. pittii isolates, the tetracyclines and polymyxins were the only antimicrobials active against all A. baumannii isolates.