Pharmacokinetic-pharmacodynamic evaluation of daptomycin, tigecycline, and linezolid versus vancomycin for the treatment of MRSA infections in four western European countries.

PURPOSE: To evaluate the usefulness of daptomycin, tigecycline, and linezolid for the treatment of MRSA infection compared with vancomycin in Belgium, the United Kingdom/Ireland, and Spain. METHODS: The methodology included the following steps: acquisition of microbiological and pharmacokinetic data, Monte Carlo simulation, estimation of the probability of target attainment (PTA), and calculation of the cumulative fraction of response (CFR). RESULTS: We showed that differences in the susceptibility of MRSA strains among countries may justify differences in the antibiotic dose selection. Two, 3, and 4 g daily of vancomycin seem be adequate in Belgium, Spain, and United Kingdom/Ireland respectively. The CFR obtained with 50 mg tigecycline every 12 h was higher in Spain than in Belgium and the United Kingdom/Ireland, but with the highest dose (100 mg q12h) the CFR was always 100%. At least 8 mg/kg daptomycin is necessary in United Kingdom/Ireland, but 4 mg/kg may be sufficient in Spain, and probably in Belgium. Six hundred mg q12h linezolid may be adequate in the four countries. CONCLUSION: Our study reinforces the idea that the local MIC distribution must be considered in order to increase the probability of success of empirical treatment and must be periodically updated.

Activity of doripenem against extended-spectrum beta-lactamase-producing Enterobacteriaceae and Pseudomonas aeruginosa isolates.

The in vitro activity of doripenem was evaluated against a recent collection of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and Pseudomonas aeruginosa isolates (201 ESBL-producing Enterobacteriaceae [153 Escherichia coli and 48 Klebsiella pneumoniae] and 201 P. aeruginosa). Comparator agents included amikacin, tobramycin, ciprofloxacin, cefepime, cefotaxime, ceftazidime piperacillin-tazobactam, imipenem, and meropenem. Both doripenem and meropenem inhibited 100% of the ESBL-producing Enterobacteriaceae at 4 microg/mL. Doripenem is active against ESBL-producing Enterobacteriaceae and P. aeruginosa isolates. Its activity is similar to that of meropenem and slightly better than that of imipenem. The results of this study suggest that doripenem could be an alternative therapeutic agent for infections caused by these organisms.

In vitro activity of tigecycline against Bacteroides species.

OBJECTIVES: To ascertain the current susceptibility patterns of members of the Bacteroides fragilis group in our hospital and to assess the in vitro activity of tigecycline against these organisms. METHODS: A total of 400 non-duplicate clinical isolates of the B. fragilis group collected from 2000 to 2002 were studied. Susceptibility testing was performed according to the reference agar dilution method described by the NCCLS. The following antimicrobials were tested: tigecycline, clindamycin, metronidazole, chloramphenicol, cefoxitin, imipenem, amoxicillin-clavulanate and piperacillin-tazobactam. RESULTS: All strains were susceptible to metronidazole and chloramphenicol. For clindamycin and cefoxitin, the overall susceptibility rates were 59.5% and 83%, respectively. Imipenem and piperacillin-tazobactam were the most active beta-lactam agents tested. Tigecycline inhibited 89.8% of the strains at a concentration of 8 mg/L with an MIC range of 16 mg/L. By comparing the MIC50 and MIC90 values of tigecycline among the various species of the group, B. fragilis, Bacteroides thetaiotaomicron and Bacteroides vulgatus were the most susceptible (MIC50/MIC90s of 0.5-1/8 mg/L). CONCLUSIONS: Tigecycline exhibited activity against most isolates of the B. fragilis group tested. These results indicate that tigecycline may be useful in the treatment and prophylaxis of infections involving these organisms.

In vitro activities of tigecycline against erythromycin-resistant Streptococcus pyogenes and Streptococcus agalactiae: mechanisms of macrolide and tetracycline resistance.

The activity of tigecycline was tested against erythromycin-resistant streptococci (107 Streptococcus pyogenes and 98 Streptococcus agalactiae strains). The presence of erythromycin and tetracycline resistance genes was determined by PCR. Among S. pyogenes strains the most prevalent gene was mef(A) (91.6%). The erm(B) gene was the most prevalent (65.3%) among S. agalactiae strains. Tigecycline proved to be very active against all the isolates tested (MIC at which 90% of the isolates tested were inhibited, 0.06 micro g/ml), including those resistant to tetracycline.

Prevalencia y tratamiento de las infecciones por grampositivos en los servicios de medicina interna de hospitales españoles: Estudio IGP / Prevalence and treatment of Gram-positive infections in internal medicine departments of Spanish hospitals: IGP Study

La finalidad de este estudio fue conocer el enfoque terapéutico y la tendencia de las infecciones por grampositivos, en los hospitales españoles, en lo referente a prevalencia, origen, localización y etiología, así como las características de los pacientes, enfermedades de base, gravedad y factores predisponentes. Se compararon, mediante análisis estadístico, los resultados de dos estudios de prevalencia multicéntricos, de 1994-1995 el primero y de 1998 el segundo. Encontramos un descenso estadísticamente significativo en el porcentaje de pacientes infectados (45,8 por ciento vs. 32,8 por ciento; p <0.001), pero un aumento en el de infección por grampositivos (14,4 por ciento vs. 20,6 por ciento; p <0.001), que se refleja en el aumento del empleo de glucopéptidos (17,1 por ciento vs. 31,2 por ciento; p = 0.002). También aumentó el uso de quinolonas. Las enfermedades de base más frecuentes fueron cardiopatías y diabetes mellitus; se observó una disminución del número de pacientes infectados por el virus de la inmunodeficiencia humana y de usuarios de drogas por vía parenteral. El descenso de la infección extrahospitalaria convirtió la nosocomial en la más frecuente en el segundo estudio, en el cual aumentó la presencia de factores predisponentes (52,3 por ciento vs. 79,2 por ciento; p <0.001), siendo los más comunes vía periférica, inmovilización y sonda vesical. La bacteriemia se mantuvo como infección más frecuente, disminuyendo las infecciones de vías respiratorias bajas y aumentando las de piel y tejidos blandos. El microorganismo más frecuente y en significativo aumento fue Staphylococcus aureus (27,2 por ciento vs. 47,9 por ciento; p <0.001), mientras que la incidencia del neumococo disminuyó (15,0 por ciento vs. 5,2 por ciento; p = 0.012). Se concluye que, a pesar del descenso en el porcentaje de infectados y en la gravedad, queda patente la tendencia al aumento de las infecciones por grampositivos, principalmente bacteriemia, y a combatirlos con tratamientos más agresivos, que pueden reflejar el aumento de aislamientos resistentes (AU)

Microbiología de las infecciones neumocócicas. Resistencia a los antibióticos / No disponible

No disponible

Erythromycin and clindamycin resistance and telithromycin susceptibility in Streptococcus agalactiae.

The rates of resistance to erythromycin and clindamycin among Streptococcus agalactiae strains isolated in our hospital increased from 4.2 and 0.8% in 1993 to 17.4 and 12.1%, respectively, in 2001. Erythromycin resistance was mainly due to the presence of an Erm(B) methylase, while the M phenotype was detected in 3.8% of the strains. Telithromycin was very active against erythromycin-resistant strains, irrespective of their mechanisms of macrolide resistance.

[Prevalence and treatment of Gram-positive infections in internal medicine departments of Spanish hospitals: IGP Study]. / Prevalencia y tratamiento de las infecciones por grampositivos en los servicios de medicina interna de hospitales españoles: Estudio IGP.

This study aimed to identify therapeutic approaches and the tendencies of Gram-positive infections in Spanish hospitals in terms of prevalence, origin, location and etiology, as well as the characteristics of patients with these infections, their underlying illnesses, the severity and predisposing factors. We used statistical analysis to compare the results of two multicenter prevalence studies, the first from 1994-1995, and the second in 1998. We found a statistically significant decrease in the percentage of infected patients (45.8% vs. 32.8%; p <0.001), but an increase in infections by Gram-positive microorganisms (14.4% vs. 20.6%; p <0.001), which was reflected in the increased use of glycopeptides (17.1% vs. 31.2%; p = 0.002). The use of quinolones also increased. The most common underlying illnesses were heart disease and diabetes mellitus, and there was a reduction in the number of patients infected by HIV and in users of parenteral medication. The decrease in outpatient infections indicated that nosocomial infection was more frequent in the second study, in which the number of predisposing factors increased (52.3% vs. 79.2%; p <0.001), the most common of which were peripheral line, immobilization and a bladder catheter. Bacteremia was the most frequent infection, and there was a reduction in lower respiratory tract infections and an increase in skin and soft tissue infections. Staphylococcus aureus was the most frequently found microorganism and showed a significant increase in incidence (27.2% vs. 47.9%; p <0.001), whereas pneumococcus showed a decrease (15.0% vs. 5.2%; p = 0.012). It was concluded that despite the decrease in the percentage of infected patients and severely ill patients, there is an increase in Gram-positive infections, especially bacteremia, and in the use of more aggressive treatments. This may reflect the increase in resistant isolates.

Comparative activity of linezolid and other new agents against methicillin-resistant Staphylococcus aureus and teicoplanin-intermediate coagulase-negative staphylococci.

The activity of linezolid was determined against 225 recently isolated methicillin-resistant Staphylococcus aureus (MRSA) and 20 methicillin-resistant coagulase-negative staphylococci (CoNS) with decreased levels of susceptibility to teicoplanin. Linezolid activity was compared with other new agents (quinupristin-dalfopristin, trovafloxacin, moxifloxacin, levofloxacin and telithromycin) and six other antimicrobials (erythromycin, clindamycin, gentamicin, vancomycin, teicoplanin and rifampicin). The in vitro activity of linezolid was similar to that of vancomycin. Linezolid inhibited all MRSA strains at between 0.1 and 2 mg/L and all CoNS strains tested at between 0.2 and 0.5 mg/L. These results suggest that linezolid would be useful for the treatment of infections involving these organisms.

In vitro activities of MK-0826 and 16 other antimicrobials against Bacteroides fragilis group strains.

The activity of MK-0826, a new carbapenem, against 309 Bacteroides fragilis group strains was investigated and compared with that of 11 other beta-lactam and 5 non-beta-lactam agents. MK-0826 showed excellent activity (MICs ranged from < or =0.06 to 4 microg/ml). The new carbapenem may be useful in the treatment of mixed anaerobic infections involving B. fragilis group strains.

Endophthalmitis caused by Listeria monocytogenes.

Listeria monocytogenes was isolated from the aqueous chamber of an immunodepressed patient with acute hypertensive uveitis, who developed a dark hypopyon and pigment dispersion. No extraocular septic focus was found. Treatment was successful with intravitreal vancomycin, anterior chamber irrigation with vancomycin, orally administered ciprofloxacin, and topical fortified vancomycin.

Comparative in vitro activities of linezolid, quinupristin-dalfopristin, moxifloxacin, and trovafloxacin against erythromycin-susceptible and -resistant streptococci.

The in vitro activities of the new agents linezolid, quinupristin-dalfopristin, moxifloxacin, and trovafloxacin were determined and compared with those of penicillin, clindamycin, and four macrolides against 53 erythromycin-resistant Streptococcus pneumoniae, 117 S. pyogenes (64 erythromycin-susceptible and 53 -resistant), and 101 S. agalactiae (53 erythromycin-susceptible and 48 -resistant) isolates. Differentiation of macrolide resistance phenotypes was performed by the double-disk method. The genetic basis for macrolide resistance in 52 strains was also determined. The M phenotype was found in 84.9, 6.3, and 1.9% of S. pyogenes, S. agalactiae, and S. pneumoniae isolates, respectively. These strains were susceptible to miocamycin and clindamycin. Strains with the inducible phenotype accounted for 27.1% of S. agalactiae isolates and 9.4% each of S. pyogenes and S. pneumoniae isolates. All erythromycin-resistant isolates were also resistant to the 14- and 15-membered macrolides tested. Strains with all three phenotypes were susceptible to

[Bacteremias in a university hospital: study of etiologic agents and their sensitivity patterns]. / Bacteriemias en un hospital universitario: estudio de los agentes etiológicos y de sus patrones de sensibilidad.

OBJECTIVE: To determine the bacterial etiology of bacteremic episodes recorded at our hospital during 1995 and their antimicrobial susceptibility patterns. METHODS: The microbiological records of all bacteremic episodes detected at our hospital from January to December 1995 were analysed. The susceptibility patterns of the 334 gram-positive aerobic isolates to 11 antimicrobials and of 236 gram-negative aerobic isolates to 16 antimicrobial agents were determined. The reference agar dilution method was used for these determinations. RESULTS: The incidence of bacteremia was 19.3/1,000 admissions. Gram-positive aerobic bacteria accounted for 56.6% of monomicrobial bacteremias; the microorganisms recovered most frequently were coagulase-negative staphylococci (22.4%), Escherichia coli (16.5%) and Staphylococcus aureus (14.2%); 75 polymicrobial episodes were recorded. Over half of bacteremic episodes occurred at medical services. Hematologic diseases and solid tumours were the most common underlying diseases. No resistance to glycopeptides was observed among the staphylococci studied. The incidence of resistance to vancomycin in enterococci was small (1.5%). The aminoglycosides tested and some beta lactams showed good activity against the gram-negative bacilli studied. CONCLUSIONS: To carry out an epidemiologic surveillance of bacteremic episodes occurring at every hospital it is necessary to provide information on trends observed in the etiology of such infections, possible outbreaks, antimicrobial resistance, and uncommon pathogens.

[Vancomycin-resistant enterococci: in vitro activity of quinupristin / dalfoprostin (RP 59500)]. / Enterococos resistentes a vancomicina: actividad in vitro de quinupristina/dalfopristina (RP 59500).

BACKGROUND: The recent emergence of glycopeptide-resistant enterococci limits the treatment of enterococcal infections. The aim of this study was to evaluate the in vitro activity of a new streptogramin, quinupristin/dalfopristin, against 30 clinical isolates of vancomycin-resistant enterococci and compared with those of other 15 antimicrobials. MATERIAL AND METHODS: Enterococci were identified by using Rapid ID 32 Strep system. Genotyping of the isolates was performed by PCR. The MICs of quinupristin/dalfopristin were determined by the agar dilution technique recommended by the NCCLS. Susceptibilities to the rest of antibiotics tested (teicoplanin, ampicillin, penicillin, imipenem, doxycicline, chloramphenicol, gentamicin, streptomycin, rifampin, levofloxacin, fleroxacin, trovafloxacin, sparfloxacin, pefloxacin and clinafloxacin) were determined by using the E test. beta-lactamase production was examined with nitrocefin disks. RESULTS: Quinupristin/dalfopristin has demonstrated excellent activity against Enterococcus faecium (MIC90' 2 micrograms/ml). Enterococcus faecalis was considerably less susceptible than E. faecium, at concentration of 4 micrograms/ml inhibited only 31% of tested strains. For doxycicline 77% of strains were susceptible. Only five isolates were susceptible to clinafloxacin; the other quinolones tested displayed poor activity. Resistance to chloramphenicol was detected in 47% of isolates. None of the isolates produced beta-lactamase. CONCLUSIONS: This study indicates that vancomycin-resistant enterococci are often concomitantly resistant to multiple antibiotics. Quinupristin/dalfopristin was the most active agent tested against E. faecium strains. On the basis of these results quinupristin/dalfopristin could be a therapeutic option for the treatment of vancomycin-resistant E. faecium infections.

Activities of new antimicrobial agents (trovafloxacin, moxifloxacin, sanfetrinem, and quinupristin-dalfopristin) against Bacteroides fragilis group: comparison with the activities of 14 other agents.

The antimicrobial activities of trovafloxacin, moxifloxacin, sanfetrinem, quinupristin-dalfopristin, and 14 other antimicrobial agents against 218 Bacteroides fragilis group strains were determined. A group of 10 imipenem-resistant strains were also tested. Imipenem, meropenem, and sanfetrinem had the lowest MICs of all of the beta-lactams. Quinupristin-dalfopristin inhibited all of the strains at 2 microg/ml. Overall, the MICs of trovafloxacin and moxifloxacin for 90% of the strains tested were 1 and 2 microg/ml, respectively.

Peritonitis caused by Haemophilus parainfluenzae in a patient undergoing continuous ambulatory peritoneal dialysis.

We report a case of peritonitis in a patient undergoing continuous ambulatory peritoneal dialysis. Haemophilus parainfluenzae biotype III was recovered in pure culture from dialysis fluid.

In-vitro susceptibilities of species of the Bacteroides fragilis group to newer beta-lactam agents.

The in-vitro activities of imipenem and four beta-lactam-beta-lactamase inhibitor combinations were tested against 816 strains of the Bacteroides fragilis group, and compared with other anti-anaerobic agents. None of the strains was resistant to metronidazole, and only one was resistant to chloramphenicol. Mezlocillin and piperacillin were moderately active, while clindamycin was the least active. Rates of resistance varied between various species. The new beta-lactam agents tested showed excellent activity; piperacillin-tazobactam and imipenem were the most active. The emergence of strains that are resistant to these agents, observed in this study, suggests there is a need to perform periodic antimicrobial susceptibility tests.