Antimicrobial activity of doripenem against Gram-negative pathogens: results from INVITA-A-DORI Brazilian study

In vitro activity of doripenem and comparator antimicrobial agents was evaluated against Gram-negative bacilli recently isolated from Brazilian private hospitals that were enrolled in the INVITA-A-DORI Brazilian Study. A total of 805 unique Gram-negative bacilli were collected from patients hospitalized at 18 medical centers between May/08 and March/09. Each hospital was asked to submit 50 single Gram-negative bacilli isolated from blood, lower respiratory tract or intraabdominal secretions. Bacterial identification was confirmed and antimicrobial susceptibility testing was performed using Clinical Laboratory Standards Institute (CLSI) microdilution method at a central laboratory. CLSI M100-S21 (2011) or US-FDA package insert criteria (tigecycline) was used for interpretation of the antimicrobial susceptibility results. Doripenem was as active as meropenem and more active than imipenem against E. coli and K. pneumoniae isolates. A total of 50.0 percent of Enterobacter spp. isolates were resistant to ceftazidime but 85.7 percent of them were inhibited at doripenem MICs < 1 µg/mL. Polymyxin B was the only agent to show potent activity against Acinetobacter spp. (MIC50/90, < 0.5/1 µg/mL) and P. aeruginosa (MIC50/90, 1/2 µg/mL). Although high rates of imipenem (53.1 percent) and meropenem (44.5 percent) resistance were detected among P. aeruginosa, doripenem showed MIC50 of 16 µg/mL against imipenem-resistant P. aeruginosa and inhibited a greater number of imipenem-resistant P. aeruginosa (10.5 percent) at MIC values of < 4 µg/mL than did meropenem (0.0 percent). In this study, doripenem showed similar in vitro activity to that of meropenem and retained some activity against imipenem-resistant P. aeruginosa isolated from Brazilian medical centers.

Antimicrobial activity of ceftobiprole against Gram-negative and Gram-positive pathogens: results from INVITA-A-CEFTO Brazilian study

Ceftobiprole is a broad-spectrum cephalosporin with potent activity against staphylococci, including those resistant to oxacillin, as well as against most Gram-negative bacilli including Pseudomonas aeruginosa. In this study, the in vitro activity of ceftobiprole and comparator agents was tested against bacterial isolates recently collected from Brazilian private hospitals. A total of 336 unique bacterial isolates were collected from hospitalized patients between February 2008 and August 2009. Each hospital was asked to submit 100 single bacterial isolates responsible for causing blood, lower respiratory tract or skin and soft tissue infections. Bacterial identification was confirmed and antimicrobial susceptibility testing was performed using CLSI microdilution method at a central laboratory. The CLSI M100-S21 (2011) was used for interpretation of the antimicrobial susceptibility results. Among the 336 pathogens collected, 255 (75.9 percent) were Gram-negative bacilli and 81 (24.1 percent) were Gram-positive cocci. Although ceftobiprole MIC50 values for oxacillin resistant strains were two-fold higher than for methicillin susceptible S. aureus, ceftobiprole inhibited 100 percent of tested S. aureus at MICs < 4 µg/mL. Polymyxin B was the only agent to show potent activity against Acinetobacter spp. (MIC50/90, 0.5/1 µg/mL), and P. aeruginosa (MIC50/90, 1/2 µg/mL). Resistance to broad-spectrum cephalosporins varied from 55.3-68.5 percent and 14.3-28.5 percent among E. coli and Klebsiella spp. isolates, respectively; with ceftobiprole MIC50 > 6 µg/mL for both species. Our results showed that ceftobiprole has potent activity against staphylococci and E. faecalis, which was superior to that of vancomycin. Our data also indicates that ceftobiprole demonstrated potency comparable to that of cefepime and ceftazidime against key Gram-negative species.

Carbapenem-resistant Pseudomonas aeruginosa outbreak in an intensive care unit of a teaching hospital

The genetic similarity of carbapenem-resistant Pseudomonas aeruginosa strains isolated in the Hospital Universitário São Francisco, Bragança Paulista, São Paulo, Brasil, was evaluated by pulsed field gel electrophoresis (PFGE). A unique clone was detected among 5 of 7 isolates, suggesting that cross-contamination might have played a role in the spread of carbapenem-resistant P. aeruginosa strains. Interestingly, a similar PFGE pattern was encountered in a P. aeruginosa strain isolated from Hospital São Paulo that was used as a PFGE control.

Antimicrobial susceptibility of Quinupristin/Dalfopristin tested against Gram-positive Cocci from Latin America: results from the global SMART (GSMART) surveillance study

Gram-positive cocci are important causes of both nosocomial and community-acquired infections, and antimicrobial resistance among these pathogens has become an important problem worldwide. Since resistance among these organisms can vary substantially by geographic location, we conducted a multicenter surveillance study with isolates from live Latin American countries (15 medical centers). Quinupristin/dalfopristin (formerly RP-59500) is a novel streptogramin combination with focused activity against Gram-positive cocci, many exhibiting emerging resistance. The in vitro activity of quinupristin/dalfopristin and 12 other antimicrobial agents were evaluated against 1,948 strains including Staphycoccus aureus (747 strains), coagulase-negative staphylococci (CoNS;446 strains), enterococci (429 strains), and various Streptococcus spp.(326 strains). Oxacillin resistance was observed in 41 percent of S. aureus (MIC,<2µg/ml or >13mm) and 40 percent of CoNS (MIC,<0.25µg/ml or >18mm). Vancomycin, teicoplanin, and quinupristin/dalfopristin (MIC90,,0.25-1µg/ml remained effective against all strains, but cross-resistance was high among other tested drugs. The quinupristin/dalfopristin MIC50 for Streptococcus pneumoniae and other streptococci was only 0.5µg/ml (13 percent to 28 percent were penicillin-resistant; 12 percent to 22 percent were macrolide-resistant). Enterococci demostrated variable inhibition by quinupristin/dalfopristin depending upon identification and the susceptibility testing method used. The demonstrated quinupristin/dalfopristin activity against Enterococcus faecium was confirmed, but potential species identification errors with various commercial systems continue to confuse susceptibility statistics, even though some strains of E. faecium confirmed by PCR-based or other molecular identification technique did have quinupristin/dalfopristin MICs of>4µg/mL. Most important, glycopeptide-resistant enterococci are rapidly emerging in Latin America, and quinupristin/dalfopristin appears active against many of these isolates as well as having potency against nearly all staphylococci and streptococci tested at<2µg/ml or having a zone diameter of>116mm. Comparisons to GSMART results from other continents show nerly identifical quinupristin/dalfopristin activity for each Gram-positive species tested. These results define the role of quinupristin/dalfopristin in Latin American medical centers and provide a bechmark for future in vitro comparisons.

Enterococcus faecalis resistant to vancomycin and teicoplanin (VanA Phenotype) isolated from a bone marrow transplanted patient in Brazil

We report for the first time in Brazil, patient from whom an Enterococcus faecalis VanA phenotype was isolated. Glycopeptide resistance is not commonly observed in Enterococcus faecalis, so this finding is of great concern since this species is responsible for 90 percent of enterococcal infections in Brazil. The isole was recovered from a surveillance rectal swab culture from a patient with acute lymphocytic (ALL). Identification to the species level was performed by conventional biomechanical tests and vitek GPI cards. Antimicrobial susceptibility testing was evaluated by use of broth microdilution and Etest (AB BIODISK, Solna, Sweden) methods. The isolate was identified as E. faecalis and was considered resistant to both vancomycin(MIC,>256µg/mL) and teicoplanin (MIC, 256 µg/mL). The isolate also showed high level resistance to gentamicin and streptomycin (MICs,>1024µg/mL), but was considered susceptible to ampicillin (MIC, 4µg/mL). Although the frequency of enterococcal infections is very low in most Latin American countries, the finding of glycopeptide (VanA) resistance in E. faecalis increases concern about apreading antimicrobial resistance in this region.

Evaluation of the in vitro activity of two fourth-generation cephalosporins against bacterial samples isolated from patients in several Brazilian Hospitals

Cefpirome and cefepime are two fourth-generation cephalosporins recently introduced in Brazil. They have a very similar range of in vitro antimicrobial activity, but some differences have been noticed. The goal of this study was to compare the in vitro activity of cefpirome and cefepime against bacterial samples isolated in Brazilian hospitals. We studied 931 samples taken from hospitalized patients between April and June, 1998. The minimum inhibitory concentration (MIC) was determined by the Etest method. The potency of cefpirome was similar to that of cefepime, except against enterococci and coagulase-negative staphylococci, where cefpirome proved 2-fold more potent. The MICs90 for cefepime were inferior to cefpirome in response to Klebsiella pneumoniae (MICs90, 24 and 96µg/mL, respectively), Pseudomonas aeruginosa (MICs90, 48 and 128µg/mL, respectively), and other Gram-negative organisms (MICs90, 64 and 256µg/mL, respectively). Despite the fact that cefpirome presented a slightly broader range of action against Gram-positive bacteria(90 percent sensitive vs. 78 percent sensitive to cefepime), and that cefepime presented an equally broad range against Gram-negative bacteria (74 percent sensitive vs. 65 percent sensitive to cefpirome), these differences were not considered clinically significant because the sensitivity differed in MIC by less than 2 dilutions. Only 16 (1.7 percent) of the 931 samples tested showed a significant difference in sensitivity. This study suggests that, except for Acinetobacter sp. and P. aeruginosa, laboratories may routinely test only cefpirome and apply the same category result to cefepime. Since category discrepancies are very rare and cefpirome is slightly less active than cefepime against Enterobacteriaceae, isolates susceptible to cefepime will certanly also be susceptible to cefpirome. To optimize the treatment of severely infected patients, especially where species such as Acinetobacter sp and P. aeruginosa are involved, we recommend that both cephalosporins be tested by using the same susceptibility test method to determine the MIC.

Avaliaçäo do perfil de sensibilidade e caracterizaçäo de Enterococcus spp. isolados em hospitais da América Latina / Antimicrobial susceptibility profile and molecular characterization of Enterococcus spp. isolated in Latin American

A vigilância de microrganismos multi-resistentes tem sido incentivada com o intuito de impedir a disseminação da resistência bacteriana aos antimicrobianos. Como o perfil de sensibilidade antimicrobiana pode variar de acordo com a região geográfica, foi conduzido um estudo de vigilância entre quatro países (l 5 centros médicos), com o objetivo de caracterizar melhor as amostras de enterococos da América Latina e avaliar o modo de disseminação de enterococos resistentes à vancomicina (ERV) nessa região. Foram analisadas 436 amostras clínicas de enterococos, coletadas em 1998 e 1999. Estas amostras foram submetidas a testes de sensibilidade para vancomicina, teicoplanina, ampicilina, gentamicina, estreptomicina, ciprofloxacina, cloranfenicol, doxiciclina e um novo antimicrobiano, quinupristindaifopristin (Synercid©). Inicialmente, foram testadas 188 amostras pelo método de micro-diluição em caldo (Brasil) e 248 amostras pelo método de difusão com discos (Argentina, Chile e Venezuela). Os enterococos que demonstraram sensibilidade diminuída à vancomicina e/ou quinupristindalfopristin, foram re-testados pelo método de micro-diluição em caldo (padrão ouro) e E-test©, e novamente identificados através dos métodos bioquímicas convencionais. A pesquisa dos genes de resistência à vancomicina (vanA, vanB, vanC1, vanC2-3 ) e a quinupristin-daifopristin (satA e satG) foi realizada através do método de reação em cadeia da polimerase (PCR), e a avaliação do modo de disseminação desta resistência foi feita por eletroforese pulsada em gel de agarose (PFGE). A ampicilina inibiu o crescimento de lOO por cento dos E. faecalís isolados no Brasil e 97 por cento dos isolados nos demais países. Entretanto, 31 por cento das amostras de E. faecíum foram resistentes à ampicilina. A resistência à vancomicina foi confirmada em 16 amostras de enterococos (3,7 por cento), sendo 14 amostras de E. faecíum e duas amostras de E. faecalis. Apenas duas destas amostras de E. faecium foram isolados na Argentina; as demais amostras foram isoladas em diferentes hospitais brasileiros (todos na cidade de São Paulo). As amostras de ERVs resistentes à vancomicina apresentaram fenótipo VanA e gene vanA, com exceção de uma única amostra isolada em Curitiba (Brasil), na qual não foi detectado nenhum gene de resistência. A resistência a quinuprístin-dalfopristin no Brasil não está relacionada aos principais genes (satA e satG) descritos para esse tipo de resistência em ...(au)

Avaliaçäo do sistema semi-automatizado microscan para identificaçäo de testes de sensibilidade de amostras de enterococos / Evaluation of the microscan semi-automated system for species identification and susceptibility testing of enterococci

O objetivo deste estudo foi avaliar a acurácia de um sistema semi-automatizados, os painéis convencionais MicroScan Positive Breakpoint Combo Type 6 (Dade MicroScan Inc., West Sacramento, CA), para identificaçäo de espécie, avaliaçäo da sensibilidade à vancomicina e à ampicilina e detecçäo de alto grau de resistência à gentamicina (HLRGN) e à estreptomicina (HLRST). Esse método foi comparado com a identificaçäo bioquímica convencional e com o método de diluiçäo em ágar (DA) para avaliaçäo de sensibilidade a antimicrobianos. Dentre as 211 amostras testadas (184 E.faecalis, 21 E.faecium e 6 näo-faecalis-näo-faecium), 95 por cento dos E.faecalis e 67 por cento dos E.faecium foram idetificados corretamente pelo MicroScan. O microScan apresentou 99,5 por cento de concordância com o método de DA para testes de sensibilidade à vancomicina e o HLRGN e o HLRST foi detectado em 92 por cento (33/36) e 84 por cento (31/37) das amostras, respectivamente. Os resultados do presente estudo mostram que este método semi-automatizado apresenta dificuldades na identificaçäo de espécies diferentes de E.faecalis, além de elevadas taxas de erros muito graves para ampicilina (11 por cento), gentamicina (8 por cento) e estreptomicina (16 por cento)

Evaluation of the in vitro activity of cefprozil relative of other oral antimicrobial agents against bacteria in clinical specimens from patients in Säo Paulo with respiratory tract infections

Cefprozil is a new oral second generation cephalosporin. Its in vitro antimicrobial activity was evaluated against 371 recent clinical isolates from patients with respiratory infections. We tested the susceptibility of 244 streptococci (96 Streptococcus pneumoniae, 105 group viridans streptococci, 32 Streptococcus agulactiae, and 11 group A ß-hemolitic streptococci) 107 Haemophilus influenfae, and 20 oxacilin-susceptible S.aureus (OSSA). The isolates were susceptibility tested cefprozil, cefactor and amoxicillin/clavulanic acid by the E-test method; and against cefadroxil, cefuroxime, cefetamet, erythromycin, and azythromycin by disk diffusion. The methods and the susceptibility categorization followed the National Committee for Clinical Laboratory Standards (NCCLS) procedures. Amoxicillin/clavulanic acid was slightly more active against H.influenzae (MIcs900.5µg/mL) than cefprozil or cefaclor(MICs90 4 and 2µg/mL respectively). Cefprozil demonstrated potent activity against streptococci. Against S. pneumoniae, cefprozil was 2-4 fold more active than cefaclor (MICs90 0.125 and 0.38µg/mL, respectively). S.pneumoniae susceptibility was 84 percent to penicillin, 95 percent to erythromycin and 97 percent to azithromycin by disk diffusion. Viridans streptococci showed higher MICs for cefprozil and cefaclor (MICs90 4 and 2µg/mL respectively). Cefprozil demonstrated potent activity against streptococci. Against S.pneumoniae, cefprozil was 2-4 fold more active than cefaclor (MICs90 0.125 and 0.38 µg/mL, respectively). S.pneumoniae susceptibility was 84 percent to penicillin, 95 percent to erythromycin and 97 percent to azithromycin by disk diffusion. Viridans streptococci showed higher MICs for cefprozil and cefaclor (MICs90 4µg/mL and 8µg/mL, respectively) and only 50 percent susceptibility to the macrolides. Cefprozil was 4-fold more active than cefaclor and as active as amoxicillin /clavulanic acid against group A ß-hemolytic streptococci and S.agalactiae. These three comounds showed similar activity against OSSA. In conclusion, cefprozil demonstrated excellent in vitro activity against bacterial species responsible for respiratory infections in Säo Paulo.

In vitro antimicrobial activity against enterococci isolated in a university hospital in Säo Paulo, Brazil

The prevalence of multiresistant enterococci (MRE) is rapidly increasing and becoming an important problem in several countries. Säo Paulo Hospital is a 600-bed tertiary hospital located in Säo Paulo, Brazil. The use of vancomycin is very high in the hospital due to the high prevalence of multi-resistant S. aureus (around 70 percent). We susceptibillity tested 250 isolates were of Enterococci consecutively collected between March, 1994 and june, 1995. Isolates were susceptibility tested using agar dilution disc diffusion BHI screen plating, and E. test. In addition to vancomycin and teicoplanin, the isolates were tested against amplicillin, gentamicin, streptomycin and RP 59-500. Methods used for susceptibility testing were compared. None of the isolates showed high-level resistence to vancomycin or teicoplanin. The MIC9Os for teicoplanin were menor igual que 1µg/mL for E. faecalis (EF,n-216), E. faecium (EFM,n=23) and for the non-faecalis-non-faecium (NFNF,n=11) species. The MIC90s for vancomycin were 2µg/mL, 4µg/mL and 4µg/mL for EF, EFM and NFNF respectively. Eight isolates (3.2 percent), 5 E. faecalis, 2 E. caseliflavus and 1 E. gallinarum presented intermediate MICs for vancomycin (6 - 12µg/mL), but they were highly susceptible to teicoplanin (MIC0.19 - 1µg/mL). The percentage of resistence to amplicillin and high-level resistence to gentamicin and streptomycin were, respectively: 4.8 percent, 26.4 percent, and 24.8 percent. In spite of the high usage of vancomycin in our hospital, the prevalence of glycopeptide resistence among enterococci seems to be low. Teicoplanin appears to be more potent than vancomycin, RP59-500, gentamicin, streptomycin and amplicillin against this genus, especially EFM and NFNF species.