Prevalence of extended-spectrum beta-lactamases in South America.

In South American countries, the class A extended-spectrum beta-lactamases (ESBLs) so far recognised belong to the CTX-M, Pseudomonas Extended Resistance (PER), SHV and TEM families. ESBL rates in South America are among the highest in the world, probably due to multiple factors. SHV- and TEM-type ESBLs have been frequently encountered, but CTX-M is endemic and widely dominant. PER-type ESBLs seem to be restricted to the southern 'cone' of South America. Community-acquired ESBLs are starting to appear.

Comparative in vitro activity of tigecycline against aerobic and facultative isolates recovered from hospitalized patients: an Argentinean multicenter study.

Tigecycline, the 9-t-butylglycylamino derivative of minocycline is the first commercially available glycylcycline exhibiting an extended spectrum of antibacterial activity due to its capacity to evade the tetracycline ribosomal and efflux resistance mechanisms. We conducted a collaborative in vitro study determining the activity of tigecycline compared to 14 antimicrobials against clinically relevant isolates obtained from adult patients hospitalized in 9 Argentinean institutions. Minimum inhibitory concentrations (MICs) were determined by the reference broth microdilution method. The number of isolates and MICs 50/90 (mg/L) for tigecycline were the following: Acinetobacter spp. 132 (0.5/1); Escherichia coli 220 (0.12/0.25); Klebsiella spp. 220 (0.5/1), Enterobacter spp. 205 (0.5/1); Serratia spp. 84 (0.5/2); Haemophilus influenzae 96 (0.25/0.5); Staphylococcus aureus 223 (0.12/0.25); Streptococcus pneumoniae 98 (

Review of pharmacokinetic, pharmacodynamic and clinical studies with a modern combination of amoxicillin/sulbactam.

Amoxicillin/sulbactam is a modern antimicrobial combination. This combination proved to be useful for the treatment of several infections caused by different microorganisms, mainly with the beta-lactamase-producing species. In this review we present the most relevant pharmacokinetic, pharmacodynamic and clinical information associated with its use.

[Consensus for antimicrobial susceptibility testing for Enterobacteriaceae. Subcommittee on Antimicrobials, SADEBAC (Argentinian Society of Clinical Bacteriology), Argentinian Association of Microbiology]. / Consenso sobre las pruebas de sensibilidad a los antimicrobianos en Enterobacteriaceae.

Taking into account previous recommendations from the National Committee for Clinical Laboratory Standards (NCCLS), the Antimicrobial Committee, Sociedad Argentina de Bacteriología Clínica (SADEBAC), Asociación Argentina de Microbiología (AAM), and the experience from its members and some invited microbiologists, a consensus was obtained for antimicrobial susceptibility testing and interpretation in most frequent enterobacterial species isolated from clinical samples in our region. This document describes the natural antimicrobial resistance of some Enterobacteriaceae family members, including the resistance profiles due to their own chromosomal encoded beta-lactamases. A list of the antimicrobial agents that should be tested, their position on the agar plates, in order to detect the most frequent antimicrobial resistance mechanisms, and considerations on which antimicrobial agents should be reported regarding to the infection site and patient characteristics are included. Also, a description on appropriate phenotypic screening and confirmatory test for detection of prevalent extended spectrum beta-lactamases in our region are presented. Finally, a summary on frequent antimicrobial susceptibility profiles and their probably associated resistance mechanisms, and some infrequent antimicrobial resistance profiles that deserve confirmation are outlined.

Consenso sobre las pruebas de sensibilidad a los antimicrobianos en Enterobacteriaceae / Consensus for antimicrobial susceptibility testing for Enterobacteriaceae

En este documento se elaboraron una serie de recomendaciones para el ensayo, lectura, interpretación e informe de las pruebas de sensibilidad a los antimicrobianos para las enterobacterias aisladas con mayor frecuencia de especímenes clínicos. Se adoptaron como base las recomendaciones del National Committee for Clinical Laboratory Standards (NCCLS) de los EEUU, los de la subcomisión de Antimicrobianos, de la Sociedad Argentina de Bacteriología Clínica (SADEBAC), división de la Asociación Argentina de Microbiología (AAM) y de un grupo de expertos invitados. En él se indican las resistencias naturales de los diferentes miembros que integran la familia Enterobacteriaceae y se analiza la actividad de las diferentes beta-lactamasas cromosómicas, propias de cada especie, sobre las penicilinas, cefalosporinas y carbapenemes. Se recomiendan los antimicrobianos que se deberían ensayar, ubicados estratégicamente, para detectar los mecanismos de resistencia más frecuentes y cuales se deberían informar de acuerdo a la especie aislada, el sitio de infección y el origen de la cepa (intra o extrahospitalario). Se detallan los métodos de "screening" y de confirmación fenotipíca para detectar beta-lactamasas de espectro extendido (BLEE) que son más adecuados a nuestra realidad. Por último, se mencionan patrones infrecuentes de sensibilidad/resistencia que deberían verificarse y los perfiles de sensibilidad que pueden hallarse en las distintas enterobacterias en relación con los probables mecanismos de resistencia. Se debe resaltar que el contenido de este documento debe ser considerado como recomendaciones realizadas por expertos argentinos basadas en una revisión de la literatura y datos personales.

Taking into account previous recommendations from the National Committee for Clinical Laboratory Standards (NCCLS), the Antimicrobial Committee, Sociedad Argentina de Bacteriología Clínica (SADEBAC), Asociación Argentina de Microbiología (AAM), and the experience from its members and some invited microbiologists, a consensus was obtained for antimicrobial susceptibility testing and interpretation in most frequent enterobacterial species isolated from clinical samples in our region. This document describes the natural antimicrobial resistance of some Enterobacteriaceae family members, including the resistance profiles due to their own chromosomal encoded beta-lactamases. A list of the antimicrobial agents that should be tested, their position on the agar plates, in order to detect the most frequent antimicrobial resistance mechanisms, and considerations on which antimicrobial agents should be reported regarding to the infection site and patient characteristics are included. Also, a description on appropriate phenotypic screening and confirmatory test for detection of prevalent extended spectrum beta-lactamases in our region are presented. Finally, a summary on frequent antimicrobial susceptibility profiles and their probably associated resistance mechanisms, and some infrequent antimicrobial resistance profiles that deserve confirmation are outlined.

Consenso sobre las pruebas de sensibilidad a los antimicrobianos en Enterobacteriaceae. / [Consensus for antimicrobial susceptibility testing for Enterobacteriaceae. Subcommittee on Antimicrobials, SADEBAC (Argentinian Society of Clinical Bacteriology), Argentinian Association of Microbiology]

Taking into account previous recommendations from the National Committee for Clinical Laboratory Standards (NCCLS), the Antimicrobial Committee, Sociedad Argentina de Bacteriología Clínica (SADEBAC), Asociación Argentina de Microbiología (AAM), and the experience from its members and some invited microbiologists, a consensus was obtained for antimicrobial susceptibility testing and interpretation in most frequent enterobacterial species isolated from clinical samples in our region. This document describes the natural antimicrobial resistance of some Enterobacteriaceae family members, including the resistance profiles due to their own chromosomal encoded beta-lactamases. A list of the antimicrobial agents that should be tested, their position on the agar plates, in order to detect the most frequent antimicrobial resistance mechanisms, and considerations on which antimicrobial agents should be reported regarding to the infection site and patient characteristics are included. Also, a description on appropriate phenotypic screening and confirmatory test for detection of prevalent extended spectrum beta-lactamases in our region are presented. Finally, a summary on frequent antimicrobial susceptibility profiles and their probably associated resistance mechanisms, and some infrequent antimicrobial resistance profiles that deserve confirmation are outlined.

[Consensus on antimicrobial sensitivity tests in gram-positive cocci. Subcommittee on Antimicrobials, SADEBAC (Argentinian Society of Clinical Bacteriology), Argentinian Association of Microbiology]. / Consenso sobre las pruebas de sensibilidad a los antimicrobianos en cocos gram-positivos.

Antimicrobial susceptibility testing is mainly performed in Argentina by disk diffusion method, following National Committee for Clinical Laboratory Standards (NCCLS) recommendations. We worked out new recommendations for the reporting and interpretation of this test when dealing with gram-positive cocci, in accordance to local trends and epidemiology. General considerations for performing the diffusion assay, quality control, and an update on susceptibility testing for gram-positive cocci are reported in this first document. The present update should be considered as a group of recommendations summarized by Argentinean experts and as the result of a consensus meeting coordinated by the Subcomisión de Antimicrobianos of the Sociedad Argentina de Bacteriología Clínica (Asociación Argentina de Microbiología). Experts in antimicrobial agents were convened in order to prepare this final document. These recommendations take into account local needs, affordability and availability to be used in current practice, tending to contribute to the correct antimicrobial treatment election, according to the particular microorganism and the infection sites.

Consenso sobre las pruebas de sensibilidad a los antimicrobianos en cocos gram-positivos / Consensus for antimicrobial susceptibility testing for gram-positive cocci

El antibiograma por difusión en agar con discos se encuentra ampliamente difundido en nuestro medio y se basa primariamente en las recomendaciones del National Committee for Clinical Laboratory Standards (NCCLS). En este documento se elaboraron una serie de recomendaciones para el ensayo, lectura, interpretación e informe de las pruebas de sensibilidad a los antimicrobianos en cocos gram-positivos, adaptadas a la realidad argentina. En esta primera etapa se redactaron las consideraciones generales para la realización de la prueba por difusión, los controles de calidad internos para todos los microorganismos y una actualización sobre las pruebas de sensibilidad en cocos gram-positivos. Se debe resaltar que el contenido de este documento debe ser considerado como recomendaciones realizadas por expertos argentinos y que son el resultado de reuniones de consenso organizadas por la Subcomisión de Antimicrobianos de la Sociedad Argentina de Bacteriología Clínica, división de la Asociación Argentina de Microbiología. Se formó un equipo de trabajo integrado por expertos en antimicrobianos y a partir de una propuesta inicial, basada en una revisión de la literatura se fueron elaborando diversos documentos de trabajo que fueron mejorados después de ser debatidos por los miembros del grupo de trabajo hasta llegar al documento final. El criterio general fue elaborar recomendaciones acordes a las necesidades de nuestro país que puedan utilizarse en la práctica diaria con el objeto de colaborar en la adecuada elección del tratamiento antibiótico según la especie bacteriana aislada y la localización de la infección.

Consenso sobre las pruebas de sensibilidad a los antimicrobianos en cocos gram-positivos / Consensus for antimicrobial susceptibility testing for gram-positive cocci

El antibiograma por difusión en agar con discos se encuentra ampliamente difundido en nuestro medio y se basa primariamente en las recomendaciones del National Committee for Clinical Laboratory Standards (NCCLS). En este documento se elaboraron una serie de recomendaciones para el ensayo, lectura, interpretación e informe de las pruebas de sensibilidad a los antimicrobianos en cocos gram-positivos, adaptadas a la realidad argentina. En esta primera etapa se redactaron las consideraciones generales para la realización de la prueba por difusión, los controles de calidad internos para todos los microorganismos y una actualización sobre las pruebas de sensibilidad en cocos gram-positivos. Se debe resaltar que el contenido de este documento debe ser considerado como recomendaciones realizadas por expertos argentinos y que son el resultado de reuniones de consenso organizadas por la Subcomisión de Antimicrobianos de la Sociedad Argentina de Bacteriología Clínica, división de la Asociación Argentina de Microbiología. Se formó un equipo de trabajo integrado por expertos en antimicrobianos y a partir de una propuesta inicial, basada en una revisión de la literatura se fueron elaborando diversos documentos de trabajo que fueron mejorados después de ser debatidos por los miembros del grupo de trabajo hasta llegar al documento final. El criterio general fue elaborar recomendaciones acordes a las necesidades de nuestro país que puedan utilizarse en la práctica diaria con el objeto de colaborar en la adecuada elección del tratamiento antibiótico según la especie bacteriana aislada y la localización de la infección. (AU)

Consenso sobre las pruebas de sensibilidad a los antimicrobianos en cocos gram-positivos. / [Consensus on antimicrobial sensitivity tests in gram-positive cocci. Subcommittee on Antimicrobials, SADEBAC (Argentinian Society of Clinical Bacteriology), Argentinian Association of Microbiology]

Antimicrobial susceptibility testing is mainly performed in Argentina by disk diffusion method, following National Committee for Clinical Laboratory Standards (NCCLS) recommendations. We worked out new recommendations for the reporting and interpretation of this test when dealing with gram-positive cocci, in accordance to local trends and epidemiology. General considerations for performing the diffusion assay, quality control, and an update on susceptibility testing for gram-positive cocci are reported in this first document. The present update should be considered as a group of recommendations summarized by Argentinean experts and as the result of a consensus meeting coordinated by the Subcomisión de Antimicrobianos of the Sociedad Argentina de Bacteriología Clínica (Asociación Argentina de Microbiología). Experts in antimicrobial agents were convened in order to prepare this final document. These recommendations take into account local needs, affordability and availability to be used in current practice, tending to contribute to the correct antimicrobial treatment election, according to the particular microorganism and the infection sites.

[Multicenter study in southern South America of the in vitro activity of telithromycin in strains with defined resistance phenotypes isolated from community-acquired respiratory infections]. / Estudio multicéntrico en el Cono Sur Americano de la actividad comparativa in vitro de telitromicina en cepas con fenotipos definidos de resistencia asociadas a infecciones respiratorias adquiridas en la comunidad.

Telithromycin was the first ketolide to be approved in Europe and is in the approval process in the United States. It is structurally related to the macrolides; it has a keto group in the C3 position rather than cladinose. A carbamate group is also present at C11-C12. As a result, it has a reduced induction of the MLSB resistance mechanism (erm gene), it is not affected by the flux mechanism (mef gene), it has higher stability at low pH and has increased intrinsic activity compared with clarithromycin and azithromycin. Phase III studies have shown telithromycin to be effective in the treatment of community-acquired upper and lower respiratory tract infections. Its long half-life allows for oral once-daily dosing. From a pharmacokinetic point of view, its activity has been shown to be AUC(24h)/MIC dependent. It is active against bacteria involved in atypical pneumonia. The aim of our study was to determine the activity of telithromycin in isolates with defined resistance phenotypes obtained from community-acquired respiratory tract infections. Twelve centers in Argentina, Chile, Paraguay and Uruguay participated in the study. Each center collected three strains of the following species and resistance patterns: S. pyogenes, S. pneumoniae with resistance or intermediate resistance to oxacillin, erythromycin-resistant S. pneumoniae, clindamycin-resistant S. pneumoniae, oxacillin-susceptible S. aureus, erythromycin-resistant S. aureus, ampicillin-susceptible and -resistant M. catarrhalis and H. influenzae. Agar diffusion susceptibility tests with NeoSensitabs tablets (Rosco, Denmark) were carried out at each center. Isolates were sent to the coordinating center, where MICs were determined using agar microdilution and the Seppala test was used to determine the resistance mechanism to macrolides. The 327 isolates received were susceptible to telithromycin. Eighty percent of the erythromycin-resistant S. pneumoniae isolates were likely resistant due to a flux mechanism, and all those resistant to clindamycin were resistant due to the erm inducible mechanism. Only 20 out of 36 strains of clindamycin-resistant S. pneumoniae and 25 of the 36 ampicillin-resistant H. influenzae strains could be collected, thereby showing that these resistance patterns are less common in the participating South American countries than in other areas. The in vitro activity of telithromycin suggests that it is a promising antibacterial drug for the treatment of community-acquired respiratory tract infections.

Estudio multicéntrico en el Cono Sur Americano de la actividad comparativa in vitro de telitromicina en cepas con fenotipos definidos de resistencia asociadas a infecciones respiratorias adquiridas en la comunidad / Multicenter study in southern South America of the in vitro activity of telithromycin in strains with defined resistance phenotypes isolated from community-acquired respiratory infections

La telitromicina es el primer cetólido aprobado en Europa y en vías de aprobación en Estados Unidos. Su estructura deriva de los macrólidos. Presenta en C3 un grupo ceto en lugar de cladinosa y un sustituyente unido a carbamato en C11-C12. Como consecuencia, tiene menor capacidad de inducción del mecanismo de resistencia MLSB (gen erm), no resulta afectado por el mecanismo de flujo (gen mef), tiene mayor estabilidad en el medio ácido gástrico y presenta una acción intrínseca aumentada en relación a claritromicina y azitromicina. La telitromicina ha demostrado su eficacia en estudios de fase III en infecciones respiratorias de vías altas y bajas adquiridas en la comunidad. Su larga vida media le permite ser administrada por vía oral en una sola dosis diaria. Bajo el punto de vista farmacodinámico se ha demostrado que su actividad es dependiente del cociente AUC24h/CMI. Tiene actividad frente a bacterias productoras de neumonías atípicas. Nuestro interés fue determinar su actividad en cepas seleccionadas según su fenotipo de resistencia, aisladas de infecciones respiratorias. El estudio incluyó 12 centros del Cono Sur Americano. Cada uno de ellos recolectó tres cepas de cada una de las siguientes especies y resistotipos: S. pyogenes, S. pneumoniae resistente o con resistencia intermedia a oxacilina, S. pneumoniae resistente a eritromicina, S. pneumoniae resistente a clindamicina, S. aureus sensible a oxacilina, S. aureus resistente a eritromicina, M. catarrhalis y H. influenzae sensible y resistente a ampicilina. En cada centro se determinó la sensibilidad a diversos antibacterianos por el método de difusión con tabletas NeoSensitabs (Rosco, Dinamarca), y en el Centro Coordinador se determinó la CMI por macrodilución en agar, así como el mecanismo de resistencia a macrólidos por el test de Seppala. Las 327 cepas recibidas fueron sensibles a telitromicina. El 80 por ciento de las cepas de S. pneumoniae resistentes a eritromicina fue resistente, probablemente debido al mecanismo de flujo, y todas las resistentes a la clindamicina lo fueron por erm inducible. Sólo 20 de 36 cepas de S. pneumoniae resistentes a clindamicina pudieron ser recuperadas, así como 25 de 36 H. influenzae resistentes a ampicilina, demostrando que estos resistotipos son menos frecuentes en el Cono Sur Americano que en otras áreas. La telitromicina se presenta como un antibacteriano prometedor para el tratamiento de las infecciones respiratorias adquiridas en la comunidad (AU)

[Escherichia coli eradication from the blader urine by amoxicillin-sulbactam. Intrinsic activity of the inhibitor]. / Erradicación de Escherichia coli de la orina vesical por amoxicilina-sulbactam. Actividad intrínseca del inhibidor.

RATIONALE: At urine concentrations obtained after the oral administration of amoxicillin-sulbactam (500/500 mg) this combination inhibits roughly 90% of Escherichia coli and Proteus mirabilis strains. AIMS: To administer amoxicilin-sulbactam 875/125 mg and to determine: a) minimum inhibitory concentration (MIC) of sulbactam for E. coli and P. mirabilis; b) urine inhibitory titres power (UIT) against amoxicillin-resistant E. coli or P. mirabilis; c) urine concentrations of sulbactam; and to verify whether sulbactam 125 mg as single drug, attains a high enough UIT to support the intrinsic action of the inhibitor; and to compare the activity of amoxicillin-sulbactam and amoxicillin-clavulanate and that of sulbactam and clavulanate. METHODS: Twelve healthy volunteers received a single oral dose of amoxicillin-sulbactam 875/125 mg or amoxicillin-clavulanate 875/125 mg, according to a randomized cross-over design. Urine samples were drawn at: 0 (basal), 2, 4, and 6 hours after dosing. Urine pH, specific gravidity and UIP were assessed. Thirty nine strains isolated from urine samples were used: 30 TEM-1 producing E. coli strains and 3 extended spectrum CTX-M-2 betalactamase-producing E. coli; and 6 P. mirabilis resistant to both combinations. In 6 healthy volunteers, sulbactam 125 mg was administered orally and UIT against E. coli (MIC amoxicillin > 2048 mg/l) was assessed. RESULTS AND DISCUSSION: MIC-90 for amoxicillin plus sulbactam or clavulanate were similar to those for sulbactam or clavulanate alone, without any difference attributable to the chemical composition of the urine. The activity of amoxicillin plus the inhibitors could be due, not only to the inhibition of betalactamase but also to the intrinsic effect of the inhibitor. Both combinations showed an equivalent inhibitory activity. Two-hour UIT remained high for the entire 6-h evaluation period. Sulbactam concentration far exceed sulbactam MIC for the 6h-period, inhibiting urine E. coli. We disagree with the cut-off limit proposed for intermediate values of NCCLS, which, for these antimicrobial are 16/8, a value lower than those obtained in urine samples after the administration of betalactamase inhibitors. This may be an explanation for the beneficial effect of amoxicillin-sulbactam in the recovery of uncomplicated lower urinary tract infections in women when the involved strains were considered resistant by diffusional methods.

Outcome of cephalosporin treatment for serious infections due to apparently susceptible organisms producing extended-spectrum beta-lactamases: implications for the clinical microbiology laboratory.

Although extended-spectrum beta-lactamases (ESBLs) hydrolyze cephalosporin antibiotics, some ESBL-producing organisms are not resistant to all cephalosporins when tested in vitro. Some authors have suggested that screening klebsiellae or Escherichia coli for ESBL production is not clinically necessary, and when most recently surveyed the majority of American clinical microbiology laboratories did not make efforts to detect ESBLs. We performed a prospective, multinational study of Klebsiella pneumoniae bacteremia and identified 10 patients who were treated for ESBL-producing K. pneumoniae bacteremia with cephalosporins and whose infecting organisms were not resistant in vitro to the utilized cephalosporin. In addition, we reviewed 26 similar cases of severe infections which had previously been reported. Of these 36 patients, 4 had to be excluded from analysis. Of the remaining 32 patients, 100% (4 of 4) patients experienced clinical failure when MICs of the cephalosporin used for treatment were in the intermediate range and 54% (15 of 28) experienced failure when MICs of the cephalosporin used for treatment were in the susceptible range. Thus, it is clinically important to detect ESBL production by klebsiellae or E. coli even when cephalosporin MICs are in the susceptible range (

Variations in the prevalence of strains expressing an extended-spectrum beta-lactamase phenotype and characterization of isolates from Europe, the Americas, and the Western Pacific region.

To evaluate the prevalence of extended-spectrum beta-lactamase (ESBL)-producing strains among species of Enterobacteriaceae, a microdilution susceptibility test was performed with strains of Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, and Salmonella species that were isolated as part of the SENTRY project. The highest percentage of ESBL phenotype (defined as a minimum inhibitory concentration [MIC] > or =2 microg/mL for ceftazidime, ceftriaxone, or aztreonam) was detected among K. pneumoniae strains from Latin America (45%), followed by those from the Western Pacific region (25%), Europe (23%), the United States (8%), and Canada (5%). P. mirabilis and E. coli strains for which MICs of extended-spectrum cephalosporins or monobactams were elevated also were more prominent in Latin America. Testing with ceftazidime revealed more isolates with elevated MICs than did testing with ceftriaxone or aztreonam. ESBL strains showed high levels of co-resistance to aminoglycosides, tetracycline, trimethoprim-sulfamethoxazole, and ciprofloxacin. Imipenem remains highly effective against ESBL strains. Organisms expressing an ESBL are widely distributed worldwide, although prevalence rates are significantly higher in certain geographic regions.

Bacterial resistance to antimicrobial agents in Latin America. The giant is awakening.

Resistant bacteria are emerging in Latin America as a real threat to the favorable outcome of infections in community- and hospital-acquired infections. Despite present extensive surveillance, healthcare workers who most need the information may be unaware of this growing problem. Outbreaks of meningococci with diminished susceptibility to penicillin have been reported in the region; a constant increase of resistance to penicillin in pneumococci and poor activity of commonly used oral antibiotics for the treatment of community-acquired urinary tract infections have made the treatment of these infections more difficult. Reports from tertiary hospitals are similar to many other areas of the world, with increasing frequency of Klebsiella pneumoniae-carrying extended-spectrum beta-lactamase, multiresistant strains of Pseudomonas aeruginosa and Acinetobacter baumanni in ICU settings, and reports of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. A surveillance network readily accessible to those who prescribe antibiotics in Latin America is highly desirable.

Epidemiology of ciprofloxacin resistance and its relationship to extended-spectrum beta-lactamase production in Klebsiella pneumoniae isolates causing bacteremia.

A prospective study of Klebsiella pneumoniae bacteremia was performed in 12 hospitals in 7 countries. Of 452 episodes of bacteremia, 25 (5.5%) were caused by K. pneumoniae that was resistant in vitro to ciprofloxacin. Extended-spectrum beta-lactamase (ESBL) production was detected in 15 (60%) of 25 ciprofloxacin-resistant isolates, compared with 68 (16%) of 427 ciprofloxacin-susceptible strains (P=.0001). Multivariate analysis revealed that risk factors for ciprofloxacin resistance in K. pneumoniae included prior receipt of a quinolone (P=.0065) and an ESBL-producing strain (P=.012). In all, 18% of ESBL-producing isolates were also ciprofloxacin-resistant. Pulsed-field gel electrophoresis showed that 11 of the 15 ciprofloxacin-resistant ESBL-producing strains belonged to just 4 genotypes, suggesting that patient-to-patient transmission of such strains occurred. The close relationship between ESBL production and ciprofloxacin resistance is particularly worrisome because the first reported instance of plasmid-mediated ciprofloxacin resistance has been in an isolate of K. pneumoniae also possessing an ESBL.

Comparative in-vitro activity of levofloxacin against isolates of bacteria from adult patients with community-acquired lower respiratory tract infections.

This study was conducted to evaluate the activity of levofloxacin in comparison with a range of antibacterial agents against recent isolates obtained consecutively from patients with community-acquired pneumonia (CAP) or acute exacerbation of chronic bronchitis (AECB) during the period 1995 to 1996. Susceptibility testing was carried out by either microdilution or the Etest, and interpreted according to NCCLS breakpoints. The activity of levofloxacin was compared with that of amoxycillin, amoxycillin-clavulanate, cefuroxime, cefixime, erythromycin, roxithromycin, clarithromycin, azithromycin, ofloxacin and ciprofloxacin. Clinically significant numbers of bacteria were recovered from 31 CAP and 94 AECB specimens. The predominant bacterial species in the CAP specimens were Streptococcus pneumoniae (21 isolates) and Haemophilus influenzae (four isolates). The AECB isolates mainly consisted of S. pneumoniae (38%), Moraxella catarrhalis (26%), H. influenzae (19%) and Pseudomonas aeruginosa (10%). The overall percentage susceptible of the isolates for each antibiotic was: amoxycillin, 64%; amoxycillin-clavulanate, 89%; cefuroxime, 87%; cefixime, 78%; erythromycin, 85%; roxithromycin, 87%; clarithromycin, 87%; azithromycin, 85%; ofloxacin, 95%; ciprofloxacin, 95%; and levofloxacin, 97%. The activities of levofloxacin and the other agents were also compared against 40 S. pneumoniae isolates, of which 20 were penicillin-non-susceptible, recovered from CAP and AECB specimens during the period 1994 to 1996. These strains were all susceptible to levofloxacin, but only 50% were susceptible to ciprofloxacin and 80% to ofloxacin. Twenty M. catarrhalis, 20 H. influenzae and 20 methicillin-susceptible S. aureus isolates were also all susceptible to levofloxacin. Furthermore, 20 community-acquired P. aeruginosa isolates showed similar percentage susceptible rates to levofloxacin and ciprofloxacin. These in-vitro results suggest that levofloxacin may be useful in the treatment of community-acquired lower respiratory tract infections.

Characterization of beta-lactamase gene blaPER-2, which encodes an extended-spectrum class A beta-lactamase.

Plasmidic extended-spectrum beta-lactamases of Ambler class A are mostly inactive against ceftibuten. Salmonella typhimurium JMC isolated in Argentina harbors a bla gene located on a plasmid (pMVP-5) which confers transferable resistance to oxyiminocephalosporins, aztreonam, and ceftibuten. The beta-lactamase PER-2 (formerly ceftibutenase-1; CTI-1) is highly susceptible to inhibition by clavulanate and is located at a pI of 5.4 after isoelectric focusing. The blaPER-2 gene was cloned and sequenced. The nucleotide sequence of a 2.2-kb insert in vector pBluescript includes an open reading frame of 927 bp. Comparison of the deduced amino acid sequence of PER-2 with those of other beta-lactamases indicates that PER-2 is not closely related to TEM or SHV enzymes (25 to 26% homology). PER-2 is most closely related to PER-1 (86.4% homology), an Ambler class A enzyme first detected in Pseudomonas aeruginosa. An enzyme with an amino acid sequence identical to that of PER-1, meanwhile, was found in various members of the family Enterobacteriaceae isolated from patients in Turkey. Our data indicate that PER-2 and PER-1 represent a new group of Ambler class A extended-spectrum beta-lactamases. PER-2 so far has been detected only in pathogens (S. typhimurium, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis) isolated from patients in South America, while the incidence of PER-1-producing strains so far has been restricted to Turkey, where it occurs both in members of the family Enterobacteriaceae and in P. aeruginosa.