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Activity of tigecycline against nosocomial secondary peritonitis isolates collected along 18 months in 29 Spanish hospitals was tested by Etest in a central laboratory, considering Food and Drug Administration (FDA)/British Society for Antimicrobial Chemotherapy (BSAC)/European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. A total of 600 facultative/aerobic isolates (392 Gram negative, 208 Gram positive) and 100 anaerobes were tested. None of the 220 Escherichia coli isolates was resistant to tigecycline (MIC(50)/MIC(90) = 0.25/0.5 microg/mL), with 0.5% (FDA breakpoint) and 3.6% (BSAC/EUCAST breakpoint) intermediate strains. All Extended-spectrum beta-lactamase (ESBL)-producing E. coli isolates (15 strains), all Klebsiella pneumoniae, and Klebsiella oxytoca isolates (42 strains) were susceptible to tigecycline. No isolates resistant to tigecycline were found among Streptococcus viridans, Staphylococcus aureus, and Enterococcus faecium, but 18.9% of Enterococcus faecalis strains were intermediate following BSAC/EUCAST breakpoints. All (but 1) isolates of the Bacteroides fragilis group (n = 45) were tigecycline susceptible, as well as Gram-positive anaerobes. Tigecycline offers an adequate activity profile against isolates from secondary peritonitis when tested by Etest regardless of the breakpoints used for categorization., (2010 Elsevier Inc. All rights reserved.)

A 1-year prospective multicenter study was performed to explore the significance of the presence of enterococci in cultures of peritoneal fluid from patients with secondary bacterial peritonitis in seven Spanish hospitals. The clinical records of patients with positive peritoneal fluid cultures were reviewed and distributed into cases (patients with cultures yielding enterococci) and controls (patients with cultures not yielding enterococci). Of a total of 158 records, 38 (24.1%) were cases and 120 (75.9%) were controls. The percentages or the scores (cases versus controls) for the variables included in the multivariate analysis were as follows: age of >50 years, 89.5% versus 68.3%; malignancy, 39.5% versus 18.3%; chronic obstructive pulmonary disease (COPD), 15.8% versus 4.2%; postoperative peritonitis, 55.3% versus 30.1%; nosocomial onset, 57.9% versus 34.2%; a higher Charlson comorbidity index, 3.29 +/- 3.38 versus 1.84 +/- 2.31; APACHE II score, 10.71 +/- 4.37 versus 8.76 +/- 5.49; ultimately or rapidly fatal disease, 63.2% versus 34.8%; need for surgical reintervention, 36.1% versus 15.1%; and admission to an intensive care unit, 45.9% versus 30.8%. In the multivariate analysis, enterococci were associated only with postoperative peritonitis (P = 0.009; odds ratio [OR] = 5.0; 95% confidence interval [CI] = 1.49 to 16.80), a higher Charlson comorbidity index (P = 0.002; OR = 1.30; 95% CI = 1.11 to 1.54), and COPD (P = 0.046; OR = 6.50; 95% CI = 1.04 to 40.73). The results of this study showed that enterococci were associated with comorbidity. An association with mortality could not be demonstrated.

Objectives: To determine C(max) tigecycline activity in the presence/absence of physiological concentrations of human albumin with free fraction concentrations as controls., Methods: Killing curves (final inoculum: 1.0-5.0 x 10(7) cfu/mL) were performed with 0.88 mg/L final concentrations (serum C(max) after a 100 mg 1 h infusion) in Mueller-Hinton broth supplemented with Ca(2+) and Mg(2+) (MH) and in MH with 4 g/dL human albumin. Controls were curves in MH with concentrations similar to the free fraction (fC(max) = 0.17 mg/L) calculated using protein binding. Activity was measured as log(10) initial inoculum reduction (log(10) initial inoculum-log(10) at 12 h/24 h). Target strains (tigecycline MIC/MBC; mg/L) were: methicillin-resistant Staphylococcus aureus heteroresistant to vancomycin (0.12/0.25); Enterococcus faecium (0.12/0.25); Escherichia coli producing extended-spectrum beta-lactamase (0.12/0.25); and Acinetobacter baumannii (0.25/1)., Results: At 24 h the fC(max) produced mean decreases of < or =0.1 cfu/mL for all strains, in contrast to the bactericidal activity (mean >3 log(10) reduction) provided by C(max) concentrations in the presence or absence of albumin for E. coli and E. faecium, and an activity nearly bactericidal for S. aureus (mean approximately 2.8 log(10) reduction). In the case of the A. baumannii isolate the C(max) in the presence or absence of albumin produced a mean reduction of 2.56 log(10) cfu/mL at 12 h (time of one dosing interval), with a bacteriostatic profile when considering 24 h colony counts (similar counts at 0 and 24 h)., Conclusions: Correcting the total concentration for the reported literature binding values is unreliable since tigecycline antibacterial activity was greater than that suggested by the free fraction of the drug.

The second national prevalence study of Pseudomonas aeruginosa has been carried out in Spain. A total of 1250 clinical isolates of P. aeruginosa were collected from 127 hospitals in 1 week in 2003 and the resistance data gathered from the isolates was compared with those of the first study in 1998 (1014 isolates from 136 hospitals). Antimicrobial susceptibility testing was performed in both studies in the same laboratory. The most active antimicrobials were piperacillin, piperacillin-tazobactam, and amikacin (< or =10% resistant) and resistance to these antimicrobials did not change over the time. The least active were ofloxacin and gentamicin (> or =30% resistant). From 1998 to 2003, resistance increased significantly to ciprofloxacin (23% vs. 28%, respectively, p=0.015); ofloxacin (30% vs. 37%, p=0.002); imipenem (14% vs. 18%, p=0.017) and meropenem (8% vs. 13%, p <0.001). Resistance to aztreonam (23%), ceftazidime (16%), cefepime (20%), ticarcillin (13%) and tobramycin (11%) remained stable. Isolates from inpatients were significantly more resistant than those from outpatients to all antimicrobials, with the exception of fluoroquinolones and aminoglycosides (p <0.01). Isolates from outpatients were significantly more resistant to these two groups (p <0.05) than to other antimicrobials. In Spain, from 1998 to 2003, the susceptibility pattern of P. aeruginosa to antimicrobial agents has changed. Isolates have become significantly more resistant to fluoroquinolones and carbapenems. However, resistance to beta-lactams and aminoglycosides remains stable.