Clinical utilization of bacteriophages: a new perspective to combat the antimicrobial resistance in Brazil

ABSTRACT Due to the emergence of multi-drug resistant bacteria, and the evident limitation in therapeutic options, alternatives to combat bacterial infections have been sought. One of these is phage therapy, which is the use of bacterial viruses to kill pathogenic bacteria responsible for the infection. These viruses called bacteriophages are very abundant organisms in the world and are harmless to humans. There are several advantages in using phage therapy, especially against multi-drug resistant pathogens, which tend to be dominated by individual strains. The advantages include fewer collateral effects such as lower disturbance of gut microbiota and less antimicrobials consumption, which itself leads to reducing antibiotic resistance rates. Unfortunately, few clinical studies have been initiated in Brazil and this area is little explored in our country. This manuscript describes clinical evidence of successful phage utilization on pathogens considered a threat in Brazil, highlighting the benefits of a possible phage utilization as an important tool to combat antimicrobial resistance in our country.

Diversity of metallo-b-lactamase-encoding genes found in distinct species of Acinetobacter isolated from the Brazilian Amazon Region

BACKGROUND The multidrug resistance (MDR) phenotype is frequently observed in Acinetobacter baumannii, the most clinically relevant pathogenic species of its genus; recently, other species belonging to the A. calcoaceticus-A. baumannii complex have emerged as important MDR nosocomial pathogens. OBJECTIVES The present study aimed to verify the occurrence of metallo-β-lactamase genes among distinct Acinetobacter species in a hospital located in the Brazilian Amazon Region. METHODS Antimicrobial susceptibility profiles were determined by broth microdilution. The genetic relationships among these isolates were assessed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Pyrosequencing reads of plasmids carrying the bla NDM-1 gene were generated using the Ion Torrent™ platform sequencing. FINDINGS A total of six isolates carried bla NDM-1: A. baumannii (n = 2), A. nosocomialis (n = 3), and A. pittii (n = 1); three carried bla IMP-1: A. baumannii, A. nosocomialis, and A. bereziniae. Resistance to colistin was observed for an NDM-1-producing A. nosocomialis isolate. Diverse PFGE patterns and sequence types were found among A. nosocomialis and A. baumannii isolates. The bla NDM-1 sequence was inserted in a Tn125 transposon, while the bla IMP-1 was found as a gene cassette of the class 1 integron In86. MAIN CONCLUSIONS To the best of our knowledge, this is the first report describing the dissemination of bla NDM-1 among distinct Acinetobacter species recovered from the same hospital in South America.

Characterisation of plasmid-mediated rmtB-1 in Enterobacteriaceae clinical isolates from São Paulo, Brazil

OBJECTIVES The emergence of 16S rRNA methyltranferases (16 RMTAses) has jeopardised the clinical use of aminoglycosides. RmtB is one of the most frequently reported in Gram-negatives worldwide. In this study, we aimed to estimate the frequency of 16S RMTAses encoding genes in Enterobacteriaceae isolated in a three-month period from a tertiary Brazilian hospital. METHODS All Gram-negatives classified as resistant to amikacin, gentamicin, and tobramycin by agar screening were selected for analysis. The presence of 16SRMTases encoding genes was verified by polymerase chain reaction (PCR). Antimicrobial susceptible profile was determined by broth microdilution. The genetic relationship among these isolates was accessed by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Selected RmtB-producing isolates were characterised by whole genome sequencing (WGS) analysis. RESULTS Twenty-two of 1,052 (2.1%) Enterobacteriaceae were detected as producers of RmtB-1 [Klebsiella pneumoniae (n = 21) and Proteus mirabilis (n = 1)]. blaKPC-2 was identified among 20 RmtB-1-producing K. pneumoniae isolates that exhibited an identical PFGE and MLST (ST258) patterns. Two K. pneumoniae isolates, the A64216 (not harboring bla KPC-2), A64477 (harboring bla KPC-2) and one P. mirabilis isolate (A64421) were selected for WGS. rmtB-1 and bla KPC-2 genes were carried by distinct plasmids. While a plasmid belonging to the IncFIIk group harbored rmtB-1 in K. pneumoniae, this gene was carried by a non-typable plasmid in P. mirabilis. In the three analysed plasmids, rmtB-1 was inserted on a transposon, downstream a Tn2. CONCLUSION Our findings suggested that the rmtB-1 was harbored by plasmids distinct from those previously reported in Bolivia and China. It suggests that multiple mobilization events might have occurred in South America.

Online continuing interprofessional education on hospital-acquired infections for Latin America

Abstract Introduction: Latin America is a large and diverse region, comprising more than 600 million inhabitants and one million physicians in over 20 countries. Resistance to antibacterial drugs is particularly important in the region. This paper describes the design, implementation and results of an international bi-lingual (Spanish and Portuguese) online continuing interprofessional interactive educational program on hospital-acquired infections and antimicrobial resistance for Latin America, supported by the American Society for Microbiology. Methods: Participation, satisfaction and knowledge gain (through pre and post tests) were used. Moreover, commitment to change statements were requested from participants at the end of the course and three months later. Results: There were 1169 participants from 19 Latin American countries who registered: 57% were physicians and 43% were other health care professionals. Of those, 1126 participated in the course, 46% received a certificate of completion and 54% a certificate of participation. There was a significant increase in knowledge between before and after the course. Of 535 participants who took both tests, the grade increased from 59 to 81%. Commitments to change were aligned with course objectives. Discussion: Implementation of this educational program showed the feasibility of a continent-wide interprofessional massive course on hospital acquired-infections in Latin America, in the two main languages spoken in the region. Next steps included a new edition of this course and a "New Challenges" course on hospital-acquired infections, which were successfully implemented in the second semester of 2015 by the same institutions.

Susceptibility rates in Latin American nations: report from a regional resistance surveillance program (2011)

OBJECTIVE: To establish a resistance (R) surveillance program monitoring antimicrobial susceptibility patterns in Latin America (LATAM; Argentina [ARG], Brazil [BRA], Chile, Colombia [CBA], Costa Rica, Ecuador [ECU], Guatemala [GUA], Mexico [MEX], Panama [PAN], Peru, and Venezuela [VEN]). METHODS: In 2011, 4979 organisms were collected from 11 nations (20 laboratories) for susceptibility testing in a central laboratory design. Antimicrobials were tested by CLSI methods and results interpreted by CLSI and EUCAST breakpoints. Most common Gram-positive (Staphylococcus aureus [SA, 921], other staphylococci [CoNS; 299], enterococci [218], Streptococcus pneumoniae [SPN; 182], β-haemolytic streptococci [115]) and Gram-negative (E. coli [EC; 644], Klebsiella spp. [KSP; 517], Enterobacters [272], Pseudomonas aeruginosa [PSA; 586], Acinetobacters [ACB; 494]) pathogens were analyzed against linezolid (LZD), vancomycin (VAN), tigecycline (TIG), colistin (COL), cefoperazone/sulbactam (C/S), and amikacin (AMK). RESULTS: MRSA rates varied from 29% (CBA, BRA) to 79% (Peru); but LZD (MIC90, 2 mg/L), TIG (MIC90, 0.12mg/L) and VAN (MIC90, 1mg/L) covered all strains. Enterococci showed a 14% VRE rate, highest in BRA and MEX; all inhibited by TIG and daptomycin, but not LZD (three non-susceptible with G2576T mutations or cfr). Penicillin-R among SPN and viridans streptococci was 51.6 and 41.1%, respectively. LZD overall R against Gram-positives was 0.3%. High ESBL rates were observed in EC (54-71%) and KSP (>50%) from GUA, MEX and Peru, and six nations, respectively. Carbapenem-R in KSP was 9%, highest rates associated with KPC in BRA, CBA, ECU, PAN and VEN; also a NDM-1 in KSP from CBA. AMK, TIG, C/S and carbapenems were the broadest-spectrum agents tested against Enterobacteriaceae. Only COL inhibited >90% of PSA; COL and TIG (<2 mg/L) covered >85% of ACB. CONCLUSIONS: LATAM nations demonstrated variable levels of antimicrobial R especially among Enterobacteriaceae (β-lactamase-mediated), PSA and ACB. MRSA (48%), VRE (14%) and multidrug-R SPN were also regional therapeutic challenges.

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.

Antimicrobial susceptibility of gram-positive bacteria isolated in brazilian hospitals participating in the SENTRY Program (2005-2008)

We report the antimicrobial susceptibility patterns of the most frequently isolated Gram-positive bacteria in the Brazilian hospitals participating in the SENTRYAntimicrobial Surveillance Program. The strains were consecutively collected (one per patient) between January 2005 and September 2008 and susceptibility tested by reference broth microdilution methods at the JMI Laboratories (North Liberty, Iowa, USA). A total of 3,907 Gram-positive cocci were analyzed. The Gram-positive organisms most frequently isolated from bloodstream infections were Staphylococcus aureus (2,218 strains; 20.2 percent of total), coagulase-negative staphylococci (CoNS; 812 strains [14.7 percent]), and Enterococcus spp. (754 strains; 5.0 percent). S. aureus ranked first (28.1 percent) and Enterococcus faecalis ranked 7th (4.5 percent) among cases of skin and soft tissue infections. S. aureus was also the second most frequently isolated pathogen from patients with lower respiratory tract infections (24.9 percent of cases) after Pseudomonas aeruginosa (30.5 percent). Resistance to oxacillin was observed in 31.0 percent of S. aureus and the vast majority of oxacillin-resistant (MRSA) strains were also resistant to clindamycin, ciprofloxacin and levofloxacin. Vancomycin, linezolid and daptomycin were all very active against S. aureus strains tested (>99.9-100.0 percent susceptible), but daptomycin (MIC50, 0.25 g/mL and MIC90, 0.5 g/mL) was four- to eight-fold more potent than vancomycin (MIC50 and MIC90 of 1 g/mL) and linezolid (MIC50, 1 g/mL and MIC90, 2 g/mL). Vancomycin resistance increased significantly among enterococci during the study period, but it was restrict to only one medical center until 2007 and emerged in a second medical center in 2008. Daptomycin was the most active antimicrobial tested against enterococci in general (100.0 percent susceptible), followed by linezolid (99.9 percent susceptible), ampicillin (87.4 percent) and vancomycin (84.6 percent)...

Evaluation of the Susceptibility profiles, genetic similarity and presence of qnr gene in Escherichia coli resistant to ciprofloxacin isolated in Brazilian hospitals

Increasing quinolone resistance has been reported worldwide, mainly among clinical isolates of Escherichia coli. The objectives of this study were to determine the susceptibility profile, the genetic relatedness, and the prevalence of the qnr gene among ciprofloxacin-resistant Escherichia coli isolated from distinct Brazilian hospitals. A total of 144 ciprofloxacin-resistant Escherichia coli were isolated from 17 Brazilian hospitals between January/2002 and June/2003. The antimicrobial susceptibility testing was performed by microdilution according to NCCLS. The presence of the qnr gene was initially screened by colony blotting, and then confirmed by PCR followed by DNA sequencing. Ninety-five urinary ciprofloxacin-resistant Escherichia coli were further selected for molecular typing by pulsed-field gel electrophoresis (PFGE). Imipenem and meropenem showed the highest susceptibility rates (100.0 percent for both compounds) followed by amikacin (91.0 percent) and piperacillin/tazobactan (84.8 percent). A single ciprofloxacin-resistant Escherichia coli isolate was positive for qnr among the 144 ciprofloxacin-resistant Escherichia coli. Forty-six PFGE patterns were observed among the 95 ciprofloxacin-resistant Escherichia coli type. This study shows that therapeutic options are limited for treatment of ciprofloxacin-resistant Escherichia coli due to the presence of additional mechanisms of antimicrobial resistance, such as ESBL production. The qnr gene was uncommon among ciprofloxacin-resistant Escherichia coli clinical isolates, but its identification might indicate the emergence of this mechanism of quinolone resistance in Brazil. The great genomic variability found among the ciprofloxacin-resistant Escherichia coli highlights the importance of the appropriate use of quinolone to restrict the selection of resistant isolates.

Increased resistance to first-line agents among bacterial pathogens isolated from urinary tract infections in Latin America: time for local guidelines?

Emerging resistance phenotypes and antimicrobial resistance rates among pathogens recovered from community-acquired urinary tract infections (CA-UTI) is an increasing problem in specific regions, limiting therapeutic options. As part of the SENTRY Antimicrobial Surveillance Program, a total of 611 isolates were collected in 2003 from patients with CA-UTI presenting at Latin American medical centers. Each strain was tested in a central laboratory using Clinical Laboratory Standard Institute (CLSI) broth microdilution methods with appropriate controls. Escherichia coli was the leading pathogen (66 percent), followed by Klebsiella spp. (7 percent), Proteus mirabilis (6.4 percent), Enterococcus spp. (5.6 percent), and Pseudomonas aeruginosa (4.6 percent). Surprisingly high resistance rates were recorded for E. coli against first-line orally administered agents for CA-UTI, such as ampicillin (53.6 percent), TMP/SMX (40.4 percent), ciprofloxacin (21.6 percent), and gatifloxacin (17.1 percent). Decreased susceptibility rates to TMP/SMX and ciprofloxacin were also documented for Klebsiella spp. (79.1 and 81.4 percent, respectively), and P. mirabilis (71.8 and 84.6 percent, respectively). For Enterococcus spp., susceptibility rates to ampicillin, chloramphenicol, ciprofloxacin, and vancomycin were 88.2, 85.3, 55.9, and 97.1 percent, respectively. High-level resistance to gentamicin was detected in 24 percent of Enterococcus spp. Bacteria isolated from patients with CA-UTI in Latin America showed limited susceptibility to orally administered antimicrobials, especially for TMP/SMX and fluoroquinolones. Our results highlight the need for developing specific CA-UTI guidelines in geographic regions where elevated resistance to new and old compounds may influence prescribing decisions.

In vitro activity of tigecycline, a new glycylcycline, tested against 1,326 clinical bacterial strains isolated from Latin America

The in vitro activity of tigecycline (former GAR-936), a new semisynthetic tetracycline, was evaluated in comparison with tetracycline and other antimicrobial agents. MATERIAL AND METHODS: A total of 1,326 contemporary clinical isolates collected from the Latin American region were collected in 2000-2002 period and tested with microdilution broth according to the CLSI guidelines. The bacterial pathogens evaluated included Staphylococcus aureus (505), Streptococcus pneumoniae (269), coagulase-negative staphylococci (CoNS; 227), Haemophilus influenzae (129), Enterococcus spp. (80), Moraxella catarrhalis (54), beta-haemolytic streptococci (28), viridans group streptococci (26), and Neisseria meningitidis (8) RESULTS:Tigecycline demonstrated excellent activity against all Gram-positive cocci, with 90 percent of penicillin-resistant S. pneumoniae strains being inhibited at 0.12 æg/mL, while the same isolates had an MIC90 of > 16 æg/mL for tetracycline. All Enterococcus spp. were inhibited at 0.25 æg/mL of tigecycline. Tigecycline (MIC50, 0.25 æg/mL) was eight-fold more potent than minocycline (MIC50, 2 æg/mL) against oxacillin-resistant S. aureus (ORSA); all ORSA were inhibited at < 2 æg/mL of tigecycline. Tigecycline demonstrated excellent activity (MIC50, 0.5 æg/mL) against CoNS with reduced susceptibility to teicoplanin (MIC, 16 æg/mL). Tigecycline also showed high potency against respiratory pathogens such as M. catarrhalis (MIC50, 0.12 æg/mL) and H. influenzae (MIC50, 0.5 æg/mL). No tigecycline resistant isolates were detected when the proposed susceptible breakpoints (< 4 æg/mL) was applied. CONCLUSIONS: This results indicate that tigecycline has potent in vitro activity against clinically important pathogenic bacteria, including Gram-positive isolates resistant to both tetracycline and minocycline.

Antimicrobial susceptibility patterns of unusual nonfermentative gram-negative bacilli isolated from Latin America: report from the SENTRY Antimicrobial Surveillance Program (1997-2002)

The antimicrobial susceptibility of 176 unusual non-fermentative gram-negative bacilli (NF-GNB) collected from Latin America region through the SENTRY Program between 1997 and 2002 was evaluated by broth microdilution according to the National Committee for Clinical Laboratory Standards (NCCLS) recommendations. Nearly 74 percent of the NF-BGN belonged to the following genera/species: Burkholderia spp. (83), Achromobacter spp. (25), Ralstonia pickettii (16), Alcaligenes spp. (12), and Cryseobacterium spp. (12). Generally, trimethoprim/sulfamethoxazole (MIC50, < 0.5 æg/ml) was the most potent drug followed by levofloxacin (MIC50, 0.5 æg/ml), and gatifloxacin (MIC50, 1 æg/ml). The highest susceptibility rates were observed for levofloxacin (78.3 percent), gatifloxacin (75.6 percent), and meropenem (72.6 percent). Ceftazidime (MIC50, 4 æg/ml; 83.1 percent susceptible) was the most active beta-lactam against B. cepacia. Against Achromobacter spp. isolates, meropenem (MIC50, 0.25 æg/ml; 88 percent susceptible) was more active than imipenem (MIC50, 2 æg/ml). Cefepime (MIC50, 2 æg/ml; 81.3 percent susceptible), and imipenem (MIC50, 2 æg/ml; 81.3 percent susceptible) were more active than ceftazidime (MIC50, >16 æg/ml; 18.8 percent susceptible) and meropenem (MIC50, 8 æg/ml; 50 percent susceptible) against Ralstonia pickettii. Since selection of the most appropriate antimicrobial agents for testing and reporting has not been established by the NCCLS for many of NF-GNB species, results from large multicenter studies may help to guide the best empiric therapy.

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.

SENTRY antimicrobial surveillance program report: latin american and brazilian results for 1997 through 2001

The alarming emergence and spread of antimicrobial resistance among common bacteria threatens the effectiveness of therapy for many infections. Surveillance of antimicrobial resistance is essential to identify the major problems and guide adequate control measures. Several resistance surveillance programs have been implemented in North America and Europe in the last decade; however, very few programs have assessed antimicrobial resistance in Latin American countries. The SENTRY Antimicrobial Surveillance Program was initiated in 1997 and represents the most comprehensive surveillance program in place at the present time worldwide. The SENTRY Program collects consecutive isolates from clinically documented infections in more than 80 medical centers worldwide (10 in Latin America). The isolates are collected according to the type of infection (objectives) and susceptibility tested in a central microbiology laboratory by reference broth microdilution methods according to NCCLS guidelines. The Program also incorporated molecular typing (ribotyping and PFGE) and resistance mechanism analysis of selected isolates. In this report we present a very broad analysis of the data generated by testing almost 20,000 bacterial isolates against more than 30 antimicrobial agents. The susceptibility results (MIC50, MIC90 and percent susceptible) are presented in 11 tables according to the organism and site of infection. The data from Brazil, as well as the data from isolates collected in 2001, are analyzed separately. This report allows the evaluation of the activities numerous antimicrobial agents against clinical isolates collected in Latin American countries.

Ability of Latin America laboratories to detect antimicrobial resistance patterns: experience of the SENTRY antimicrobial surveillance program (1997-2000)

The accuracy of antimicrobial susceptibility tests is a crucial step for the clinical management of patients with serious infections. They must be reliable and precise because they will guide antimicrobial therapy. Our main objective was to compare the results of susceptibility testing performed by the SENTRY coordinator laboratory with those reported by the participating Latin American medical centers. A total of 10,277 bacterial isolates were tested by the reference broth microdilution method at the coordinator laboratory in the United States. The tests were performed and interpreted following the National Committee for Clinical Laboratory Standards (NCCLS) recommendations. Ten antimicrobial agent-organism combinations were analyzed. The susceptibility methods utilized in each of the medical centers were also evaluated. Total agreement of the results was obtained in nearly 88 percent of the antimicrobial agent-organism combinations. "Very major" (false-susceptible results) and "major errors" (false-resistant results) were observed in 12 percent and 6 percent of the cases, respectively. The highest disagreements were observed for coagulase-negative Staphylococcus - oxacillin (20 percent - very major error) and Burkholderia cepacia - imipenem (21 percent - very major error). The susceptibility method with the highest agreement rate was Etest« (92 percent) > PASCO« (91 percent) > agar dilution (91 percent) > MicroScan« (90 percent) > Vitek« (87 percent). External quality assurance data obtained by surveillance programs such as the SENTRY Antimicrobial Surveillance Program are not only helpful for detecting the emergence of patterns of antimicrobial resistance, but also to monitor the performance of the participating microbiology laboratories.

Comparação das atividades antimicrobianas de meropenem e imipenem/cilastatina: o laboratório necessita testar rotineiramente os dois antimicrobianos? / Comparative antimicrobial activity between meropenem and imipenem/cilastatina: does the clinical laboratory need to test both imipenem and meropenem routinely?

O meropenem e o imipenem representam os ßðlactâmicos com maior espectro e potência antimicrobiana, e são os únicos carbapenêmicos disponíveis para uso clínico no Brasil, nos Estados Unidos e na Europa. O meropenem apresenta atividade in vitro superior contra gramðnegativos, enquanto que o imipenem é discretamente mais ativo contra gramðpositivos. Os objetivos deste estudo são comparar as atividade in vitro destes dois carbapenêmicos e avaliar a necessidade de o laboratório clínico testáðlos em sua rotina. Os resultados da avaliação dos padrões de sensibilidade de 2.144 bacilos gramðnegativos pela técnica de microdiluição em caldo foram analisados. Contra enterobactérias, o meropenem apresentou atividade pelo menos oito vezes maior que o imipenem. Contra Pseudomonas aeruginosa, o meropenem (CIM50 de 1 µg/ml) também apresentou atividade superior à do imipenem (CIM50 de 1 µg/ml para ambos). Somente 2,7 por cento das amostras avaliadas apresentaram resultados discordantes entre os dois carbapenêmicos em termos de categoria de sensibilidade ð isto é, foram sensíveis a um e resistentes ao outro. Quarenta e seis amostras (2,14 por cento) foram sensíveis ao meropenem e resistentes ao imipenem, enquanto que somente 12 amostras (0,55 por centro) apresentaram sensibilidade ao imipenem e resistência ao meropenem. A grande maioria dos resultados discordantes (91,4 por centro) ocorreu entre as amostras de bacilos gramðnegativos nãoðfermentadores da glicose (BGNðNF). Entre as 1.350 enterobactérias testadas houve apenas cinco resultados discordantes (0,37 por cento), enquanto que entre os BGNðNF ocorreram 53 (6,67 por cento). Além disso, em cerca de 80 por cento, as amostras foram sensíveis ao meropenem e resistentes ao imipenem. Os resultados deste estudo indicam que o laboratório de microbiologia pode testar apenas um dos carbapenêmicos contra enterobactérias, considerando para o outro o mesmo resultado. É importante que os resultados dos dois carbapenêmicos sejam colocados no relatório, para que o médico possa escolher aquele que achar mais adequado. Por outro lado, para os BGNðNF, o laboratório deve realizar o teste de sensibilidade com os dois carbapenêmicos separadamente

Antimicrobial activity of linezolid against gram-positive cocci isolated in Brazil

The new oxazolidinone linezolid and other antimicrobial agents used to treat Gram-positive infections were tested against 1,585 Gram-positive cocci; 1,260 staphylococci and enterococci isolates from patients hospitalized in brazilian hospitals, and 325 S pneumoniae isolates for patients with community acquired infections. Susceptibility testing was performed using broth microdilution according to NCCLS procedures. Linezolid was the most active compound and the only drug that inhibited 100 percent of the isolates at the susceptible breakpoint (<4µg/mL). Resistance to vancomycin was very rare (99.9 percent susceptibility), and both quinupristin/dalfopristin and gatifloxacin were active against approximately 90 percent of the strains evaluated. All other comounds inhibited less than 65 percent of the isolates. The excellent in vitro Gram-positive activity by linezolid, in this study, indicate that this compound may represent an important therapeutic option for the treatment of infections caused by these pathogens in Brazil.

Patogen frequency and resistance patterns in brazilian hospitals: summary of results from three years of the sentry antimicrobial surveillance program

Pathogen frequency and resistance patterns may vary significantly from country to country and also in different hospitals within a country. Thus, regional surveillance programs are essential to guide empirical therapy and infection control measures. Methods: rank order of occurence and antimicrobial susceptibility to patogenic species causing bloodstream infections (BSI), lower respiratory tract infections (LRTI), wound or skin and soft tissue infections (WSSTI), and urinary tract infections (UTI) in hospitalized patients were determined by collecting consecutive isolates over a specified period of time, as part of the SENTRY Antimicrobial Resistance Surveillance Program (SENTRY). All isolates were tested by reference broth microdilution. Results and conclusiones: A total of 3,728 bacterial strains were obtained from january, 1997, to december, 1999, from 12 brazilian hospitals located in 4 states. The largest number of isolates were obtained from patients with BSI (2,008), followed by LRTI (822 cases), UTI (468 cases), and WSSti (430 cases). Staphylococcus aureus was the most frequently isolated patogen in general (22.8 percent-852 isolates), followed by E. coli (13.8 percent - 516 cases) and pseudomonas aeruginosa (13.3 percent - 496 cases). Staphylococcus aureus was also the most common species isolated from BSI (23.6 percent) and WSSTI (45.8 percent), and P.aeruginosa was the most frequent species isolated from patients with LRTI (29.4 percent). The main bacterial resistance problems found in this study were: imipenem resistance among P.aeruginosa (69.8 percent susceptibility) and Acinetobacter spp. (88.1 percent susceptibility): ESBL production among K. pneumoniae (48.4 percent) and E. coli (8.9 percent); resistance to third generation cephalosporin among Enterobacter spp. (68.1 percent susceptible to ceftazidime) and oxacillin resistance among S. aureus (34.0 percent) and coagulase negative staphylococci (80.1 percent). Only the carbapenems (88.1 percent to 89.3 percent susceptibility) showed reasonable activity against the Acinetobacter spp. isolates evaluated.

Perfil de sensibilidade a antimicrobianos de bactérias isoladas do trato respiratório baixo de pacientes internados em hospital brasileiros - Resultados do Programa SENTRY, 1997 e 1998 / Antimicrobial suspeceptibility of bacteria isolated from the lower respiratory tract of impatients with pneumonia in Brazilian hospital - Results from the SENTRY surveillance program, 1997 and 1998

INTRODUÇÄO: Pneumonia hospitalar é a mais fatal das infecçöes hospitalares, com taxas de mortalidade de 30 a 60 por cento. Estima-se que 15 por cento de todas as mortes associadas à hospitalizaçäo estejam diretamente relacionadas a pneumonia hospitalar. O SENTRY é um estudo de vigilância de resistência a antimicrobianos envolvendo centros médicos em todo o mundo. OBJETIVO: Avaliar a sensibilidade a antimicrobianos de bactérias isoladas no trato respiratório baixo de pacientes com pneumonia internados em hospital brasileiro. MATERIAL E MÉTODOS: Foram avaliadas 525 amostras bacterianas de 11 hospitais brasileiros, como parte do programa SENTRY. Os isolados foram testados por microdiluiçäo em caldo contra um grande número de antimicrobianos. RESULTADOS: As cinco espécies mais freqüentes foram (n/por cento): Pseudomonas aeruginosa (158/30,1 por cento), Staphylococcus aureus (103/19,6 por cento), acinetobacter spp. (68/13,0 por cento), Klebsiella spp. (50/9,5 por cento), e Enterobacter spp. (44/8,4 por cento). Essas cinco espécie representam mais de 80 por cento de toda a amostragem. A P. aeruginosa apresentou altas taxas de resistência à maioria dos antimicrobianos testados. As maiores taxas de sensibilidade foram apresentadas por piperacilina/tazobactam (71,5 por cento) e meropenem (69,0 por cento). Os compostos com maior atividade in vitro contra Acinetobacter spp. foram imipenem e meropenem (80,9 por cento de sensibiliade) seguido pela tetraciclina (63,2 porcento). A sensibilidade das amostras de Klebsiella spp. foi muito baixa. MIC = ug/mL para ceftriaxona ou ceftazidima, indicando produçäo de ESBL, foram os cabapenens (100 por cento de sensibilidade) e as quinolonas (92,0 por cento de sensibilidade). Ceftrixona foi ativa contra somente 56,8 por cento da amostras de Enterobacter spp. (MIC50, ó 1ug/mL), enquanto a cefapima foi detectada em 43,7 por cento dos isolados de S. aureus. As drogas mais ativas contra essa espécie foram: vancomicina, teicoplanina, quinupristin-dalfopristin e linezolida. CONCLUSÄO: Os resultados do presente estudo mostraram alta prevalência de Acinetobacter spp. e altas taxas de resistência entre bacilos gram-negativos quando comparados com resultados de estudos norte-americanos e europeus

Detecçäo de B-lactamases de espectro ampliado (ESBL) pelo laboratório clínico: uma revisäo crítica / Laboratory detection of extended-spectrum B-lactamase (ESBL) producing bacteria: a critical review

A grande dificuldade na detecçäo de cepas produtoras de ß-lactamases de espectro ampliado (ESBL) é decorrente de de vários fatores, incluindo a grande variedade nos tipos de ESBL e alteraçöes de potência e afinidade destas aos diferentes ß-lactâmicos. Além disso, a quantidade de ß-lactamase produzida pode variar de cepa para cepa, variando, assim, o grau de resistência. Porém, a detecçäo laboratorial desse tipo de resistência apresenta grande importância, uma vez que há vários relatos de falência terapêutica devido ao uso de cefalosporinas de terceira geraçäo e penicilinas de amplo espectro no tratamento de infecçöes causadas por cepas produtoras de ESBL que apresentavam sensibilidade in vitro aos ß-lactâmicos utilizados no tratamento. Este trabalho avalia as vantagens e desvantagens de vários métodos disponíveis, como dupla-difusäo em disco, adiçäo de ácido clavulânico a discos de antimicrobianos, fitas de Etest ESBL Screen, disco difusäo e determinaçäo da CIM utilizando breakpoints indicativos da produçäo de ESBL padronizados pelo NCCLS, teste tridimensional e Vitek