Estimating the likelihood of success with the initial empiric antimicrobial therapy in patients with nosocomial infections.

In order to estimate the likelihood of success (SL) with the initial empiric antimicrobial therapy, the following formula was constructed with data subjected to prior clinical validation in real time: SL (%) = (Nº isolates susceptible to IEAT/Nº patients with MDI) × 100. Where the numerator of the formula represents the total number of isolates recovered from the assessed type of infection, that was susceptible to any component of empiric antimicrobial therapy (IEAT) used, and the denominator represents the total number of patients with the same assessed, but microbiologically documented infection (MDI). For male hospital-acquired urinary tract infection, only imipenem reached a suitable SL value (i.e. ≥80%). In patients with hospital-acquired peritonitis, imipenem and tigecycline-ceftazidime showed the highest coverage rates. For ventilator-associated pneumonia only imipenem yielded acceptable coverage as a single drug. Implementing the present formula instead of the regular global antibiograms used to guide the selection of the initial treatment may benefit the patient outcome and improve antimicrobial usage.

Control of an outbreak of postoperative bone mucormycosis: An intervention study of contiguous cohorts.

An outbreak of postoperative bone mucormycosis following arthroscopic anterior cruciate ligament reconstruction in a tertiary referral center in Paraná, Argentina, could have been transmitted through an arthroscopic anterior cruciate ligament reconstruction-exclusive contaminated item. The outbreak was controlled after changing from a system of direct delivery of implants and instruments to the operating room without proper verification, to a controlled and centralized process; specifically, the institution's pharmacy verified the quality and traceability of implants, and instruments were processed only by the institution's central sterile services department.

Comparative time-kill study of doxycycline, tigecycline, cefazolin and vancomycin against several clones of Staphylococcus aureus.

BACKGROUND: We present herein, a comparative study assessing the bactericidal kinetics of tigecycline, doxycycline, cefazolin and vancomycin against several methicllin-susceptible (MSSA) and -resistant (MRSA) Staphylococcus aureus isolates recovered from patients of 24 different cities in Argentina. METHODS: After genotypic characterization, 20 strains (10 MRSA and 10 MSSA) were selected for time-kill studies. RESULTS: Vancomycin showed bactericidal effect (i.e. ≥3-log(10) CFU/mL decrease) against 50% and 10% of the MRSA strains at 4 x Minimal Inhibitory Concentration (MIC) and 2xMIC, respectively, after 24 h of incubation and displayed bactericidal activity against all MSSA isolates at 4xMIC. Cefazolin was bactericidal against 30% of MSSA strains at the higher concentration (4xMIC) and against 10% at 2 x MIC and MIC dose concentrations. The bactericidal magnitude of cefazolin observed after 24 h of incubation was lower than the vancomycin one. Albeit bacteriostactic, tigecycline at 2xMIC exerted a -1 to2-log decrease in the viable cell counts after 24-h incubation against 19 of the 20 S. aureus strains. Doxycycline was the least inhibitory of the antibiotics tested against both MRSA and MSSA, displaying no bactericidal activity in any of the cases and showing regrowth after 24 h of incubation at MIC level. CONCLUSION: Vancomycin at high concentrations showed the best activity. Cefazolin did not show the activity expected for a beta-lactam antibiotic against MSSA. Tigecycline may be a useful option in infections caused by MRSA, where bactericidal activity is not an exclusive requirement and doxycycline does not seem an attractive alternative in serious infections.

[Antimicrobial susceptibility testing in clinically relevant non-fermenting gram-negative bacilli: recommendations from the Antimicrobial Agents Subcommittee of the Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas, Asociación Argentina de Microbiología]. / Criterios de ensayo, interpretación e informe de las pruebas de sensibilidad a los antibióticos en los bacilos gram negativos no fermentadores de importancia clínica: recomendaciones de la Subcomisión de Antimicrobianos de la Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas, Asociación Argentina de Microbiología.

This document contains the recommendations for antimicrobial susceptibility testing of the clinically relevant non-fermenting gram-negative bacilli (NFGNB), adopted after conforming those from international committees to the experience of the Antimicrobial Agents Subcommittee members and invited experts. This document includes an update on NFGNB classification and description, as well as some specific descriptions regarding natural or frequent antimicrobial resistance and a brief account of associated resistance mechanisms. These recommendations not only suggest the antimicrobial drugs to be evaluated in each case, but also provide an optimization of the disk diffusion layout and a selection of results to be reported. Finally, this document also includes a summary of the different methodological approaches that may be used for detection and confirmation of emerging b-lactamases, such as class A and B carbapenemases.

Criterios de ensayo, interpretación e informe de las pruebas de sensibilidad a los antibióticos en los bacilos gram negativos no fermentadores de importancia clínica: recomendaciones de la Subcomisión de Antimicrobianos de la Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas, Asociación Argentina de Microbiología / Antimicrobial susceptibility testing in clinically relevant non-fermenting gram-negative bacilli: recommendations from the Antimicrobial Agents Subcommittee of the Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas, Asociación Argentina de Microbiología

En este documento se dan a conocer una serie de recomendaciones para el ensayo, la lectura, la interpretación y el informe de las pruebas de sensibilidad a los antimicrobianos para los bacilos gram negativos no fermentadores (BGNNF) que se aíslan en humanos. Se adoptaron como base las recomendaciones internacionales, las de la Subcomisión de Antimicrobianos de la Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas y las de un grupo de expertos invitados. Se incluye, además, la nomenclatura actualizada de los BGNNF y la descripción de algunas de sus características individuales, de sus resistencias naturales o habituales a los antimicrobianos de uso clínico y de los mecanismos responsables de tales resistencias. También se indican los agentes antimicrobianos que se deberían ensayar frente a las distintas especies, con la especificación de cuáles deberían ser informados, y su ubicación estratégica en las placas de cultivo para poder detectar los mecanismos de resistencia más frecuentes y relevantes. Por último, se detallan los métodos de detección y de confirmación fenotípica de la presencia de b-lactamasas emergentes en Argentina, como las carbapenemasas clases A y B.

This document contains the recommendations for antimicrobial susceptibility testing of the clinically relevant non-fermenting gram-negative bacilli (NFGNB), adopted after conforming those from international committees to the experience of the Antimicrobial Agents Subcommittee members and invited experts. This document includes an update on NFGNB classification and description, as well as some specific descriptions regarding natural or frequent antimicrobial resistance and a brief account of associated resistance mechanisms. These recommendations not only suggest the antimicrobial drugs to be evaluated in each case, but also provide an optimization of the disk diffusion layout and a selection of results to be reported. Finally, this document also includes a summary of the different methodological approaches that may be used for detection and confirmation of emerging b-lactamases, such as class A and B carbapenemases.

[Updated acute community-acquired pneumonia in adults: Guidelines for initial antimicrobial therapy based on local evidence from the South American Working Group (ConsenSur II)]. / Neumonía aguda adquirida en la comunidad en adultos: Actualización de los lineamientos para el tratamiento antimicrobiano inicial basado en la evidencia local del Grupo de Trabajo de Sudamérica (ConsenSur II).

Community-acquired pneumonia (CAP) in adults is probably one of the infections affecting ambulatory patients for which the highest diversity of guidelines has been written worldwide. Most of them agree in that antimicrobial therapy should be initially tailored according to either the severity of the infection or the presence of comorbidities and the etiologic pathogen. Nevertheless, a great variability may be noted among the different countries in the selection of the primary choice in the antimicrobial agents, even for the cases considered as at a low-risk class. This fact may be due to the many microbial causes of CAP and specialties involved, as well as the different health-care systems effecting on the availability or cost of antibiotics. However, many countries or regions adopt some of the guidelines or design their own recommendations regardless of the local data, probably because of the scarcity of such data. This is the reason why we have developed a guideline for the initial treatment of CAP by 2002 upon the basis of several local evidences in South América (ConsenSur I). However, several issues deserve to be currently rediscussed as follows: certain clinical scores other than the Physiological Severity índex (PSI) have become more popular in clinical practice (i.e. CURB-65, CRB-65); some pathogens have emerged in the región, such as community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) and Legionella spp; new evidences on the performance of the rapid test for the etiologic diagnosis in CAP have been reported (eg. urinary Legionella andpneumococcus antigens); new therapeutic considerations needs to be approached (i.e. dosage reformulation, duration of treatment, emergence of novel antibiotics and clinical impact of combined therapy). Like in the first versión of the ConsenSur (ConsenSur I), the various current guidelines have helped to organize and stratify the present proposal, ConsenSur II.

Neumonía aguda adquirida en la comunidad en adultos: actualización de los lineamientos para el tratamiento antimicrobiano inicial basado en la evidencia local del Grupo de Trabajo de Sudamérica (ConsenSur II) / Updated acute community-acquired pneumonia in adults: guidelines for initial antimicrobial therapy based on local evidence from the South American Working Group (ConsenSur II)

Community-acquired pneumonia (CAP) in adults is probably one of the infections affecting ambulatory patients for which the highest diversity of guidelines has been written worldwide. Most of them agree in that antimicrobial therapy should be initially tailored according to either the severity of the infection or the presence of comorbidities and the etiologic pathogen. Nevertheless, a great variability may be noted among the different countries in the selection of the primary choice in the antimicrobial agents, even for the cases considered as at a low-risk class. This fact may be due to the many microbial causes of CAP and specialties involved, as well as the different health-care systems effecting on the availability or cost of antibiotics. However, many countries or regions adopt some of the guidelines or design their own recommendations regardless of the local data, probably because of the scarcity of such data. This is the reason why we have developed a guideline for the initial treatment of CAP by 2002 upon the basis of several local evidences in South América (ConsenSur I). However, several issues deserve to be currently rediscussed as follows: certain clinical scores other than the Physiological Severity índex (PSI) have become more popular in clinical practice (i.e. CURB-65, CRB-65); some pathogens have emerged in the región, such as community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) and Legionella spp; new evidences on the performance of the rapid test for the etiologic diagnosis in CAP have been reported (eg. urinary Legionella andpneumococcus antigens); new therapeutic considerations needs to be approached (i.e. dosage reformulation, duration of treatment, emergence of novel antibiotics and clinical impact of combined therapy). Like in the first versión of the ConsenSur (ConsenSur I), the various current guidelines have helped to organize and stratify the present proposal, ConsenSur II.

La neumonía adquirida por adultos en la comunidad (NAC) es, probablemente, una de las infecciones que afecta a los pacientes ambulatorios para la cual se ha escrito la mayor diversidad de lineamientos en todo el mundo. La mayoría de ellos concuerdan en que el tratamiento antimicrobiano debe ser ajustado inicialmente de acuerdo con la gravedad de la infección o con la presencia de co-morbilidades y el patógeno etiológico. Aun así, se puede notar una gran variabilidad entre los diferentes países en la selección de la elección primaria de los agentes antimicrobianos, incluso en los casos considerados como de bajo riesgo. Este hecho puede deberse a las múltiples causas microbianas de la NAC y las especialidades médicas involucradas, como así también los diferentes sistemas de asistencia de salud que afectan la disponibilidad o el costo de los antimicrobianos. No obstante, muchos países o regiones adoptan alguno de los lineamientos o diseñan sus propias recomendaciones independientemente de los datos locales, probablemente debido a la escasez de dichos datos. Por esta razón desarrollamos lineamientos para el tratamiento inicial de la NAC hacia el año 2002, sobre la base de varias evidencias locales en Sudamérica (ConsenSur I). Sin embargo, varios temas merecen discutirse nuevamente como sigue: ciertos puntajes clínicos además del índice Fisiológico de Severidad (IFS) se hicieron más populares en la práctica clínica (por ej. CURB-65, CRB-65); emergieron algunos patógenos en la región, tal como Staphylococcus aureus resistente adquirido en la comunidad (SAMR-AC) y Legionella spp; se reportaron nuevas evidencias sobre el desempeño de la prueba rápida para el diagnóstico etiológico de NAC (por ejemplo, Legionella urinaria y antígenos de Streptococcus pneumoniae); deben abordarse nuevas consideraciones terapéuticas (por ej.: reformulación de la dosis, duración del tratamiento, emergencia de antimicrobianos nuevos e impacto clínico del tratamiento...

Pharmacodynamic assessment of Amoxicillin-Sulbactam against Acinetobacter baumannii: searching the optimal dose and infusion time through a human ex-vivo model

Amoxicillin-sulbactam (AMX-SUL) is an aminopenicillin/ß-lactamase inhibitor combination currently available in 29 countries and may be a suitable option for treating infections caused by Acinetobacter spp. Thus, we sought to search the optimal dosing strategy for this formulation through an ex vivo pharmacodynamic human model against Acinetobacter baumanniii. Four volunteers were randomized to receive alternatively a single dose AMX-SUL infused both either over 30 min or 3h at the following ratios (g/g): 1/0.5; 1/1, and 0/2. Time-kill studies were performed with the 0-, 0.5-, 2-, 4-, 6- and 8-h sera after dose against a clinical isolate of A. baumannii (sulbactam MIC, 4µg/mL). Bactericidal activity (i.e. a mean decrease >3 log10 CFU/mL in the viable cell counts from the initial inoculum) was displayed by the 0.5- and the 2-h sera after dose for all formulations. The 4-h sera proved inhibitory with the AMX-SUL 1g/1g formulation, albeit a trend to regrowth was observed after 24-h incubation. With the AMX-SUL 0g/2g dose, the 4-h sera proved almost bactericidal activity (i.e. a mean decrease of 2.4 log10 CFU/mL in the viable cell counts from the initial inoculum), whereas the 6-h sera was inhibitory, with a trend to regrowth after 24-h incubation. When infused over 3h, AMX-SUL 1g/0.5g and 1g/1g, bactericidal activity was displayed by the 0.5-, 2- and the 4-h sera after dose and the 6-h sera proved inhibitory with the AMX-SUL 1g/1g formulation. The present study, albeit preliminary, might give a rationale for the dosing strategy to treat infections caused by A. baumannii with sulbactam, either alone or combined with amoxicillin. A 2-g sulbactam dose seems to be optimal to be infused over 30 min with a 6-h dosing interval. When infused over 3h, AMX-SUL 1g/1g given every 6h or 8h seems a suitable dosing schedule.

Pharmacodynamic assessment of Amoxicillin-Sulbactam against Acinetobacter baumannii: searching the optimal dose and infusion time through a human ex-vivo model.

Amoxicillin-sulbactam (AMX-SUL) is an aminopenicillin/ss-lactamase inhibitor combination currently available in 29 countries and may be a suitable option for treating infections caused by Acinetobacter spp. Thus, we sought to search the optimal dosing strategy for this formulation through an ex vivo pharmacodynamic human model against Acinetobacter baumanniii. Four volunteers were randomized to receive alternatively a single dose AMX-SUL infused both either over 30 min or 3h at the following ratios (g/g): 1/0.5; 1/1, and 0/2. Time-kill studies were performed with the 0-, 0.5-, 2-, 4-, 6- and 8-h sera after dose against a clinical isolate of A. baumannii (sulbactam MIC, 4microg/mL). Bactericidal activity (i.e. a mean decrease >3 log10 CFU/mL in the viable cell counts from the initial inoculum) was displayed by the 0.5- and the 2-h sera after dose for all formulations. The 4-h sera proved inhibitory with the AMX-SUL 1g/1g formulation, albeit a trend to regrowth was observed after 24-h incubation. With the AMX-SUL 0g/2g dose, the 4-h sera proved almost bactericidal activity (i.e. a mean decrease of 2.4 log10 CFU/mL in the viable cell counts from the initial inoculum), whereas the 6-h sera was inhibitory, with a trend to regrowth after 24-h incubation. When infused over 3h, AMX-SUL 1g/0.5g and 1g/1g, bactericidal activity was displayed by the 0.5-, 2- and the 4-h sera after dose and the 6-h sera proved inhibitory with the AMX-SUL 1g/1g formulation. The present study, albeit preliminary, might give a rationale for the dosing strategy to treat infections caused by A. baumannii with sulbactam, either alone or combined with amoxicillin. A 2-g sulbactam dose seems to be optimal to be infused over 30 min with a 6-h dosing interval. When infused over 3h, AMX-SUL 1g/1g given every 6h or 8h seems a suitable dosing schedule.

Multicenter study to assess the in vitro activity of tigecycline by disk diffusion test against clinical isolates from Argentina.

BACKGROUND: Tigecycline is a new antibiotic currently used in healthcare environments where multidrug resistance is prominent. Because there is a constant potential for resistance to emerge, survey studies are needed. METHODS: Isolates collected in 20 clinical laboratories from 4 states of Argentina between November 2005 and October 2006 were tested using the disk diffusion method as described by the CLSI. RESULTS: A total of 3,182 isolates were assessed. Gram-positive cocci represented 43.4% of the total isolates [Staphylococcus aureus (878), coagulase-negative staphylococci (255), Enterococcus spp. (201), Streptococcus spp. (47)], Enterobacteriaceae 39.6% and Acinetobacter spp. 11.1%. Tigecycline proved equally active against methicillin-resistant and methicillin-susceptible staphylococci, as well as against vancomycin-resistant and vancomycin-susceptible enterococci (100% of susceptibility for all Gram-positive bacteria tested). Tigecycline susceptibility for Enterobacteriaceae, other than Proteeae tribe and Serratia spp., ranged from 88 to 100%, including against strains with resistance to third-generation cephalosporins with phenotype of extended spectrum beta-lactamases (extended spectrum beta-lactamase-positive Escherichia coli 17.7% and extended spectrum beta-lactamase-positive Klebsiella pneumoniae 50.5%). Adopting a resistant breakpoint of 16 mm, 92% of the Acinetobacter isolates were susceptible to tigecycline. CONCLUSION(S): Tigecycline was active against a wide variety of bacterial species, including most of the multidrug-resistant Gram-negative and Gram-positive bacteria. Therefore, it could be a suitable option in the treatment of infections caused by these organisms in hospitalized patients.

Comparative time-kill study of doxycycline, tigecycline, sulbactam, and imipenem against several clones of Acinetobacter baumannii.

To assess potential alternative options for the treatment of infections caused by Acinetobacter baumannii, we performed time-kill studies of doxycycline and tigecycline using several isolates recovered from patients residing in 10 different cities in Argentina. Imipenem and sulbactam were also included for comparison purposes. Eleven isolates representing 5 distinctive clones, or isolates with different susceptibility patterns within the same clone, were selected. Tubes containing cation-supplemented Mueller-Hinton broth with and without antibiotics were seeded with a log-phase inoculum of roughly 5 x 10(5) CFU/mL. By using the viable counts determined at 2-, 4-, 6-, 8-, and 24-h intervals after inoculation, a 24-h time-kill curve was constructed for each isolate. No bactericidal activity (defined as a >or=3-log(10) CFU/mL decrease in the viable cell counts with respect to the original inoculum) was observed at any time with sulbactam (4 microg/mL) or tigecycline (1 microg/mL), whereas low bactericidal rate (18% of the isolates) was shown for doxycycline (1 microg/mL) and sulbactam (16 microg/mL) after 24 h of incubation. Doxycycline (4 microg/mL) and tigecycline (8 microg/mL) displayed bactericidal activity at 24 h of incubation against 36% and 54% of the isolates, respectively, including the carbapenem-resistant isolate. Corresponding values for imipenem (1 and 4 microg/mL) against the 10 carbapenem-susceptible isolates were 60% and 90%, respectively. The present study confirms the in vitro efficacy of imipenem against A. baumannii, suggests that doxycycline could be a suitable, cost-effective, alternative option in some instances, and sheds light on the potential role of tigecycline in the treatment of infections with this organism.

A 7-year national survey on bacterial resistance in bronchoalveolar lavage from patients hospitalized in Argentina.

The purpose of this study is to undertake a nationwide survey on bacterial resistance in bronchoalveolar lavage (BAL) from patients hospitalized in Argentina. A 2-month point prevalence study was conducted twice yearly (April-May and October-November) from 1997 to 2003 by 36 Argentinean centers. Antimicrobial susceptibility data of the potential pathogens recovered from the BAL (samples containing <1% of squamous epithelial cells and bacterial counts >or=10(4) CFU/mL) of inpatients (i.e., >or=48-h hospital length of stay) with suspected hospital-acquired pneumonia (HAP) were collected on a computerized system (SIR) described previously. The survey was split into 2 periods for comparison purposes, 1997 to 2000 and 2001 to 2003. A total of 752 organisms were included. Staphylococcus aureus was the most frequent species, followed by Acinetobacter spp. and Pseudomonas aeruginosa. In both periods, more than a half of the Klebsiella pneumoniae strains displayed a phenotype of extended-spectrum beta-lactamase producer. A doubling of imipenem-resistant Acinetobacter frequency was shown from the 1st period to the 2nd one (25-48%). More than two-thirds of the S. aureus strains proved to be methicillin resistant in both periods, and a pronounced decrease of resistance rates to trimethoprim/sulfamethoxazole and rifampin was shown in the 2nd period. The present study shows the worrisome increasing bacterial resistance in BAL samples to most available antimicrobial options for treating patients with suspected HAP. Variations over time support the need for systematic tailored surveillance and compel us to establish a rational usage of antimicrobial agents in our country.

Are laboratory-based antibiograms reliable to guide the selection of empirical antimicrobial treatment in patients with hospital-acquired infections?

OBJECTIVES: Antibiograms are often taken into account to define a rational selection of an empirical antimicrobial therapy for treating patients with hospital-acquired infections. In this study, we performed a paired comparison between the antibiogram constructed with laboratory-based data and that formed with data subjected to prior clinical validation. METHODS: Between 2003 and 2005, the laboratory of microbiology printed in duplicate every individual susceptibility report corresponding to hospitalized patients and the copy was sent to the department of infection control. Every individual report was assessed in real time at the bedside of the patient by a multidisciplinary team for clinical significance and appropriateness of the specimen, as well as for the type, source and origin of the infection. Cumulative resistance rates were estimated in parallel at the laboratory with the whole data, and at the infection control department with data subjected to prior clinical validation. These rates were designated as 'laboratory-based' and 'clinically based', respectively. RESULTS: A total of 2305 individual susceptibility reports were assessed. Only 1429 (62.0%) were considered as clinically significant by the multidisciplinary team. Escherichia coli, Enterobacter cloacae, Citrobacter freundii group, Klebsiella species and Proteus mirabilis resistant to broad-spectrum cephalosporins, as well as methicillin-resistant Staphylococcus aureus, were significantly more frequent in the clinically based rates (P < or = 0.03). CONCLUSIONS: Laboratory-based data underestimate the frequency of several major resistant organisms in patients with hospital-acquired infection. Previous clinical validation of the individual susceptibility reports seems to be a suitable strategy to get more reliable data.

Does a reduction in antibiotic consumption always represent a favorable outcome from an intervention program on prescribing practice?

OBJECTIVES: In our hospital, a continuous intervention program aimed at optimizing the quality of antibiotic use was introduced by late 1999 and antibiotic consumption was a major outcome for assessment. However, healthcare conditions have been subject to change over the last five years, and a pronounced economic crisis in 2002 affected the availability of antibiotics. Therefore, we hypothesized that the consumption of these drugs could be a suitable indirect marker of the crisis. DESIGN: We performed segmented regression analysis between different periods. Variations in antibiotic consumption during periods corresponding to the four-phase intervention program (from 1999 to the first six months of 2001) were assumed to be 'intervention-induced', while those observed during the crisis period were considered as 'situation-enforced'. RESULTS: Whereas the intervention-induced (desirable) decrease of total antibiotic and carbapenem consumption proved to correlate with a decreased crude mortality rate during the control period prior to the crisis (R2, 0.82 and 0.91, respectively), the crisis-induced (undesirable) decrease in total antibiotic and carbapenem consumption correlated with an increased mortality during this phase (R2, 0.80 and 0.75, respectively). CONCLUSIONS: Our results illustrate that a reduction in antibiotic consumption does not always represent a favorable outcome from an intervention program on prescribing practice. Moreover, it may be a sensitive indirect marker of a deficient healthcare condition leading to an increase in in-hospital mortality.

Neumonía aguda extrahospitalaria: ¿demasiadas normas para el mismo problema? / Community-acquired acute pneumonia: too many guidelines for the same problem?

A mediados de 2001 se constituyó un grupo de trabajo en el Cono Sur americano (ConsenSur) integrado por profesionales con experiencia en neumonía adquirida en la comunidad (NAC), con el objetivo de diseñar una guía práctica para el manejo inicial de esta patología, concebida sobre datos locales. El documento resultante se publicó a gines de 2002. Desde entonces se generó la siguiente información en nuestra región y en el mundo: en Argentina, la tasa neumococo con alta resistencia a penicilina es 1% y la resistencia a macrólidos y levofloxacina, 14% y 1% respectivamente. A mediados de 2002, comenzó en Uruguay un brote epidémico causado por una cepa de Staphylococcus aureus resistente a meticilina de origen comunitario (SAMR-AC). A la fecha, ya son 42 los pacientes que sufrieron infección por este clon. Emergieron nuevos antibióticos, nuevas formulaciones o nuevas dosis de drogas existentes y hubo un auge de modelos farmacodinámicos. La mayor parte de la nueva información ratifica el contenido del ConsenSur, excepto i)la aparición de casos de NAC grave producidos por SAMR-AC, ii)la sugerencia de utilizar dosis más altas de levofloxacina y iii)la consideración de acortar la terapia en pacientes con NAC leve o moderada no complicada con buena evolución.

Replacement of broad-spectrum cephalosporins by piperacillin-tazobactam: impact on sustained high rates of bacterial resistance.

We have previously observed a significant reduction of ceftriaxone resistance in Proteus mirabilis associated with an increase in the use of cefepime, along with a decrease in the consumption of broad-spectrum cephalosporins (CEP). However, we did not observe such a reduction with Klebsiella pneumoniae. Therefore, we sought to determine whether replacement of CEP by piperacillin-tazobactam might be useful in reducing sustained high rates of CEP resistance by this organism. We used a 6-month "before and after model"; during the second (intervention) period, most prescriptions of CEP were changed to piperacillin-tazobactam at the pharmacy. No additional barrier precautions were undertaken. During intervention, consumption of ceftazidime decreased from 17.73 to 1.14 defined daily doses (DDD) per 1,000 patient-days (P < 0.0001), whereas that of piperacillin-tazobactam increased from 0 to 30.57 DDD per 1,000 patient-days (P < 0.0001). The levels of resistance to CEP by K. pneumoniae and P. mirabilis decreased from 68.4 and 57.9% to 37.5 and 29.4%, respectively (P < 0.05). We conclude that replacement of ceftazidime by piperacillin-tazobactam might be a suitable strategy to decrease endemic CEP resistance by K. pneumoniae and P. mirabilis, even where there are high bacterial resistance rates and irrespective of any additional precautions for controlling nosocomial infection.

Argentinean collaborative multicenter study on the in vitro comparative activity of piperacillin-tazobactam against selected bacterial isolates recovered from hospitalized patients.

The in vitro activity of piperacillin-tazobactam and several antibacterial drugs commonly used in Argentinean hospitals for the treatment of severe infections was determined against selected but consecutively isolated strains from clinical specimens recovered from hospitalized patients at 17 different hospitals from 9 Argentinean cities from different geographic areas during the period November 2001-March 2002. Out of 418 Enterobacteriaceae included in the Study 84% were susceptible to piperacillin-tazobactam. ESBLs putative producers were isolated at an extremely high rate since among those isolates obtained from patients with hospital acquired infections 56% of Klebsiella pneumoniae, 32% of Proteus mirabilis and 25% Escherichia coli were phenotypically considered as ESBLs producers Notably P.mirabilis is not considered by for screening for ESBL producers. ESBLs producers were 100% susceptible to imipenem and 70% were susceptible to piperacillin-tazobactam whereas more than 50% were resistant to levofloxacin. The isolates considered as amp C beta lactamase putative producers showed 99% susceptibility to carbapenems while 26.7% were resistant to piperacillin-tazobactam and 38.4% to levofloxacin. Noteworthy only 4% of the Enterobacteriaceae isolates were resistant to amikacin. Piperacillin-tazobactam was the most active agent against Pseudomonas aeruginosa isolates (MIC(90): 128 microg/ml; 78% susceptibility) but showed poor activity against Acinetobacter spp (MIC(90):>256 microg/ml; 21.7% susceptibility). Only 41.7% Acinetobacter spp isolates were susceptible to ampicillin-sulbactam. Piperacillin-tazobactam inhibited 100% of Haemophilus influenzae isolates (MIC(90) < 0.25 microg/ml) but only 16.6% of them were ampicillin resistant. The activity of piperacillin-tazobactam against oxacillin susceptible Staphylococcus aureus or coagulase negative staphylococci was excellent (MIC(90) 2 microg/ml; 100% susceptibility). Out of 150 enterococci 12 isolates (8%) were identified as E.faecium and only three isolates (2%), 2 E.faecium and 1 E.faecalis were vancomycin resistant. All the enterococci isolates were susceptible to linezolid. Piperacillin-tazobactam showed excellent activity (MIC(90) 2 microg/ml; 92% susceptibility). Regarding pneumococci all the isolates showed MICs of 16 microg/ml for piperacillin-tazobactam. Among 34 viridans group streptococci only 67% were penicillin susceptible and 85.2% ceftriaxone susceptible whereas piperacillin-tazobactam was very active (MIC(90) 4 microg/ml).Piperacillin-tazobactam is therefore a very interesting antibacterial drug to be used, preferably in combination (IE: amikacin-vancomycin) for the empiric treatment of severe infections occurring in hospitalized patients in Argentina. Caution must be taken for infections due to ESBL producers considering that the inoculum effect MICs can affect MIC values.

A hospitalwide intervention program to optimize the quality of antibiotic use: impact on prescribing practice, antibiotic consumption, cost savings, and bacterial resistance.

Several findings from Argentina provide compelling evidence of the need for more rational use of antimicrobial agents. Thus, a multidisciplinary antimicrobial treatment committee for the development of a hospital-wide intervention program was formed to optimize the quality of antibiotic use in hospitals. Four successive steps were developed during 6-month periods: baseline data collection, introduction of a prescription form, education, and prescribing control. Sustained reduction of drug consumption was shown during the study (R2=0.6885; P=.01). Total cost savings was 913,236 US dollars. To estimate the consumption of cefepime and aminopenicillin-sulbactam in relation to that of the third-generation cephalosporins, 2 indices were calculated: Icfp and Iams, respectively. Decreasing resistance to ceftriaxone by Proteus mirabilis and Enterobacter cloacae proved to be associated with increasing Icfp. Decreasing rates of methicillin-resistant Staphylococcus aureus were related to increasing Iams. The present study indicates that a systematic program performed by a multidisciplinary team is a cost-effective strategy for optimizing antibiotic prescribing.