Background: Extended-spectrum ␤-lactamase (ESBL)producing Escherichia coli is an increasingly important group of community pathogens worldwide. These organisms are frequently resistant to many of the antimicrobial agents usually recommended for the treatment of infections caused by E coli, such as penicillins, cephalosporins, fluoroquinolones, and trimethoprim-sulfamethoxazole. Data concerning risk factors, clinical features, and therapeutic options for such infections are scarce. Methods: A case-control study was performed to investigate the risk factors for all types of community-acquired infections caused by ESBL-producing E coli in 11 Spanish hospitals from February 2002 to May 2003. Controls were randomly chosen from among outpatients with a clinical sample not yielding ESBL-producing E coli. The clinical features of these infections were investigated in the case patients. The efficacy of fosfomycin tromethamine and amoxicillin-clavulanate potassium was observationally studied in patients with cystitis. Results: A total of 122 cases were included. Risk factors selected by multivariate analysis included the fol-Author Affiliations are listed at the end of this article.

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Acinetobacter baumannii is an important cause of nosocomial infections in many hospitals. It is difficult to control and infection caused is difficult to treat due to its high resistance in the environment and its ability to develop resistance to antimicrobials. Bacteremia, followed by respiratory tract and surgical wound infections, is the most significant infection caused by A. baumannii. The known risk factors for A. baumannii bacteremia are invasive procedures and the use of broad-spectrum antimicrobials. Consequently, episodes of bacteremia due to A. baumannii occur most frequently in critically-ill patients admitted to an intensive care unit. The clinical manifestations of bacteremia by A. baumannii are not specific. The most common sources of bacteremia are intravascular catheters and the respiratory tract. A. baumannii bacteremia is associated with a high crude mortality rate, but it is difficult to distinguish morbidity and mortality attributable to A. baumannii from that attributable to the common and severe co-morbidity in these patients. A. baumannii is a bacterium that appears to have a propensity for developing multiple antimicrobial resistance extremely rapidly. These data are disturbing because the therapeutic possibilities decrease while inappropriate antimicrobial treatment contributes to patient mortality. Generally, imipenem is the most active agent against A. baumannii. However, the description of imipenem-resistant A. baumannii strains is becoming increasingly common. The usual treatment for A. baumannii bacteremia is an active beta-lactam alone, preferably one with a limited spectrum. Before beginning treatment of a bacteremia by A. baumannii, it is very important to carry out a clinical evaluation of the patient to eliminate the possibility of a pseudobacteremia, and thereby avoid unnecessary treatment.

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Antimicrobial susceptibility testing is essential for guiding the treatment of many types of bacterial infections, especially in the current context of rising rates of antibiotic resistance. The most commonly employed methods rely on the detection of phenotypic resistance by measuring bacterial growth in the presence of the antibiotic being tested. Although these methods are highly sensitive for the detection of resistance, they require that the bacterial pathogen is isolated from the clinical sample before testing and must employ incubation times that are sufficient for differentiating resistant from susceptible isolates. Knowledge regarding the molecular determinants of antibiotic resistance has facilitated the development of novel approaches for the rapid detection of resistance in bacterial pathogens. PCR-based techniques, mass spectrometry, microarrays, microfluidics, cell lysis-based approaches and whole-genome sequencing have all demonstrated the ability to detect resistance in various bacterial species. However, it remains to be determined whether these methods can achieve sufficient sensitivity and specificity compared with standard phenotypic resistance testing to justify their use in routine clinical practice. In the present review, we discuss recent progress in the development of methods for rapid antimicrobial susceptibility testing and highlight the limitations of each approach that still remain be addressed.

Biofilm formation in 92 unrelated strains of Acinetobacter baumannii isolated in a multicentre cohort study was investigated using a microtitre plate assay. Fifty-six (63%) isolates formed biofilm. These isolates were less frequently resistant to imipenem or ciprofloxacin than were non-biofilm-forming isolates (25% vs. 47%, p 0.04; and 66% vs. 94%, p 0.004, respectively). All catheter-related urinary or bloodstream infections and the sole case of shunt-related meningitis were caused by biofilm-forming strains. Multivariate analysis revealed that treatment in an intensive care unit, ciprofloxacin resistance and isolation from a respiratory sample were associated with non-biofilm-forming isolates, while previous aminoglycoside use was associated with biofilm-forming isolates.

eWe investigated the mechanisms of resistance to carbapenems, aminoglycosides, glycylcyclines, tetracyclines, and quinolones in 90 multiresistant clinical strains of Acinetobacter baumannii isolated from two genetically unrelated A. baumannii clones: clone PFGE-ROC-1 (53 strains producing the OXA-58 ␤-lactamase enzyme and 18 strains with the OXA-24 ␤-lactamase) and clone PFGE-HUI-1 (19 strains susceptible to carbapenems). We used real-time reverse transcriptase PCR to correlate antimicrobial resistance (MICs) with expression of genes encoding chromosomal ␤-lactamases (AmpC and OXA-51), porins (OmpA, CarO, Omp33, Dcap-like, OprB, Omp25, OprC, OprD, and OmpW), and proteins integral to six efflux systems (AdeABC, AdeIJK, AdeFGH, CraA, AbeM, and AmvA). Overexpression of the AdeABC system (level of expression relative to that by A. baumannii ATCC 17978, 30-to 45-fold) was significantly associated with resistance to tigecycline, minocycline, and gentamicin and other biological functions. However, hyperexpression of the AdeIJK efflux pump (level of expression relative to that by A. baumannii ATCC 17978, 8-to 10-fold) was significantly associated only with resistance to tigecycline and minocycline (to which the TetB efflux system also contributed). TetB and TetA(39) efflux pumps were detected in clinical strains and were associated with resistance to tetracyclines and doxycycline. The absence of the AdeABC system and the lack of expression of other mechanisms suggest that tigecycline-resistant strains of the PFGE-HUI-1 clone may be associated with a novel resistance-nodulation-cell efflux pump (decreased MICs in the presence of the inhibitor Phe-Arg ␤-naphthylamide dihydrochloride) and the TetA(39) system.

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.