Risk factors for bloodstream infections due to colistin-resistant KPC-producing Klebsiella pneumoniae: results from a multicenter case-control-control study.

The increasing prevalence of colistin resistance (ColR) Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (Kp) is a matter of concern because of its unfavourable impact on mortality of KPC-Kp bloodstream infections (BSI) and the shortage of alternative therapeutic options. A matched case-control-control analysis was conducted. The primary study end point was to assess risk factors for ColR KPC-Kp BSI. The secondary end point was to describe mortality and clinical characteristics of these infections. To assess risk factors for ColR, 142 patients with ColR KPC-Kp BSI were compared to two controls groups: 284 controls without infections caused by KPC-Kp (control group A) and 284 controls with colistin-susceptible (ColS) KPC-Kp BSI (control group B). In the first multivariate analysis (cases vs. group A), previous colistin therapy, previous KPC-Kp colonization, ≥3 previous hospitalizations, Charlson score ≥3 and neutropenia were found to be associated with the development of ColR KPC-Kp BSI. In the second multivariate analysis (cases vs. group B), only previous colistin therapy, previous KPC-Kp colonization and Charlson score ≥3 were associated with ColR. Overall, ColR among KPC-Kp blood isolates increased more than threefold during the 4.5-year study period, and 30-day mortality of ColR KPC-Kp BSI was as high as 51%. Strict rules for the use of colistin are mandatory to staunch the dissemination of ColR in KPC-Kp-endemic hospitals.

Successful tigecycline lock therapy in a Lactobacillus rhamnosus catheter-related bloodstream infection.

INTRODUCTION: Catheter-related bloodstream infections very often involve the premature removal of long-term intravascular devices (LTID). The antibiotic lock therapy (ALT) represents a conservative approach to the treatment of uncomplicated infections of tunneled LTID when catheter removal is not a feasible option. CASE REPORT: We present here the first reported case of tunneled LTID bloodstream infection due to a multidrug resistant Lactobacillus rhamnosus. The patient, who had large granular lymphocytic leukemia, was successfully treated with systemic tigecycline therapy and lock therapy. CONCLUSION: Our results confirm ALT as a valid catheter-salvage strategy for the treatment of CRBSIs in clinically stable patients when catheter removal is not a feasible option, tigecycline appear to be a good option.

Antimicrobial resistance in Europe and its potential impact on empirical therapy.

The problem of microbial drug resistance is a major public health concern, due to its global dimension and alarming magnitude, although the epidemiology of resistance can exhibit remarkable geographical variability and rapid temporal evolution. The major resistance issues overall are those related to methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), Enterobacteriaceae producing extended-spectrum beta-lactamases, and multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Europe is not free from any of these issues, although their impact may be significantly different in different countries. MRSA rates are high in several European countries, but seem to have levelled off in some settings. Diffusion of VRE is still irregular. The most alarming resistance trends are those observed for Enterobacteriaceae and the Gram-negative non-fermenters, with a generalized increase in rates of resistance to the most important anti-Gram-negative agents (beta-lactams and fluoroquinolones) and the circulation of strains showing multidrug resistance phenotypes.

Treatment and control of severe infections caused by multiresistant Pseudomonas aeruginosa.

Pseudomonas aeruginosa is one of the leading causes of nosocomial infections. Severe infections, such as pneumonia or bacteraemia, are associated with high mortality rates and are often difficult to treat, as the repertoire of useful anti-pseudomonal agents is limited (some beta-lactams, fluoroquinolones and aminoglycosides, and the polymyxins as last-resort drugs); moreover, P. aeruginosa exhibits remarkable ability to acquire resistance to these agents. Acquired resistance arises by mutation or acquisition of exogenous resistance determinants and can be mediated by several mechanisms (degrading enzymes, reduced permeability, active efflux and target modification). Overall, resistance rates are on the increase, and may be different in different settings, so that surveillance of P. aeruginosa susceptibility is essential for the definition of empirical regimens. Multidrug resistance is frequent, and clinical isolates resistant to virtually all anti-pseudomonal agents are increasingly being reported. Monotherapy is usually recommended for uncomplicated urinary tract infections, while combination therapy is normally recommended for severe infections, such as bacteraemia and pneumonia, although, at least in some cases, the advantage of combination therapy remains a matter of debate. Antimicrobial use is a risk factor for P. aeruginosa resistance, especially with some agents (fluoroquinolones and carbapenems), and interventions based on antimicrobial rotation and restriction of certain agents can be useful to control the spread of resistance. Similar measures, together with the prudent use of antibiotics and compliance with infection control measures, are essential to preserve the efficacy of the currently available anti-pseudomonal agents, in view of the dearth, in the near future, of new options against multidrug-resistant P. aeruginosa strains.

Dynamics of a nosocomial outbreak of multidrug-resistant Pseudomonas aeruginosa producing the PER-1 extended-spectrum beta-lactamase.

From November 1998 to August 1999, a large outbreak occurred in the general intensive care unit of the Ospedale di Circolo in Varese (Italy), caused by Pseudomonas aeruginosa producing the PER-1 extended-spectrum beta-lactamase. A total of 108 clinical isolates of P. aeruginosa resistant to broad-spectrum cephalosporins were recovered from 18 patients. Epidemic isolates were characterized by synergy between clavulanic acid and ceftazidime, cefepime, and aztreonam. Isoelectric focusing of crude bacterial extracts detected two nitrocefin-positive bands with pI values of 8.0 and 5.3. PCR amplification and characterization of the amplicons by restriction analysis and direct sequencing indicated that the epidemic isolates carried a bla(PER-1) determinant. The outbreak was of clonal origin as shown by pulsed-field gel electrophoresis analysis. This technique also indicated that the epidemic strain was not related to three other PER-1-positive isolates obtained at the same hospital in 1997. Typing by enterobacterial repetitive intergenic consensus-PCR showed that minor genetic variations occurred during the outbreak. The epidemic strain was characterized by a multiple-drug-resistance phenotype that remained unchanged over the outbreak, including extended-spectrum cephalosporins, monobactams, aminoglycosides, and fluoroquinolones. Isolation of infected patients and appropriate carbapenem therapy were successful in ending the outbreak. Our report indicates that the bla(PER-1) resistance determinant may become an emerging therapeutic problem in Europe.

PER-1 extended-spectrum beta-lactamase production in an Alcaligenes faecalis clinical isolate resistant to expanded-spectrum cephalosporins and monobactams from a hospital in Northern Italy.

An Alicaligenes faecalis (FL-424/98) resistant to expanded-spectrum cephalosporins and aztreonam was isolated from the urine of an inpatient at the Intensive Care Unit of the Varese Hospital (Northern Italy) after antimicrobial chemotherapy with cefazolin, vancomycin, and amikacin. Clavulanic acid restored the activity of expanded-spectrum cephalosporins, suggesting the production of an extended-spectrum beta-lactamase (ESbetaL). A crude extract of FL-424/98 showed the presence of two beta-lactamase activities focusing at pH 5.3 and 7.6, respectively. The ESbetaL activity, purified by means of three chromatographic steps, was found to correspond to the pI 5.3 enzyme. Determination of kinetic parameters confirmed that the enzyme efficiently hydrolyzed expanded-spectrum cephalosporins and aztreonam. A colony-blot hybridization revealed the presence of blaPER-related sequences in FL-424/98, and sequencing confirmed the identity of this determinant with blaPER-1, previously detected in Pseudomonas aeruginosa, Acinetobacter, and Salmonella clinical isolates from Turkey. Finding of blaPER-1 in a species that can be part of the resident human microbiota raises the possibility that it could be an efficient shuttle for spreading of this resistance gene among other opportunistic pathogens that are normally members of the resident microbiota. Kinetic parameters determined for the PER-1 enzyme with some cephalosporin substrates were somewhat different from those previously reported.