Maria Adriana Cataldo

Continuous versus intermittent infusion of vancomycin for the treatment of Gram-positive infections: systematic review and meta-analysis

OBJECTIVES To summarize available evidence on the effect of continuous infusion (CoI) of vancomycin compared with intermittent infusion (InI) in adult patients with Gram-positive infections. METHODS MEDLINE, EMBASE and Cochrane databases were searched. Randomized clinical trials (RCTs) and observational studies that comparatively assessed CoI and InI of vancomycin in terms of mortality, clinical cure, toxicity rates and serum drug exposure [trough concentration (C(min)) for InI and steady-state concentration (C(ss)) for CoI; area under the curve at 24 h (AUC(24)) for both] were included. Meta-analysis was conducted combining and analysing the relative risk (RR) and computing a summary RR of the effects with 95% confidence interval (CI). The standardized mean difference was calculated for continuous outcomes. The I(2) test was calculated to assess heterogeneity across studies. RESULTS One RCT and five observational studies were included in the analysis. Compared with InI, CoI of vancomycin was associated with a significantly lower risk of nephrotoxicity (RR 0.6, 95% CI 0.4-0.9, P = 0.02; I(2)= 0). Overall mortality was not different between the two groups (RR 1.03, 95% CI 0.7-1.6, P = 0.9; I(2)= 0). CONCLUSIONS Our meta-analysis suggests that administration of vancomycin for the treatment of Gram-positive infections by CoI is associated with a significantly lower risk of nephrotoxicity when compared with InI of the drug. RCTs are needed to define the impact on mortality rate and on the pharmacodynamic activity in terms of AUC/MIC ratio.

Rapid screening tests for meticillin-resistant Staphylococcus aureus at hospital admission: systematic review and meta-analysis

Detection and eradication of meticillin-resistant Staphylococcus aureus (MRSA) represents a public health priority worldwide. Our aim was to do a systematic review and meta-analysis of randomised, non-randomised, and observational studies to summarise the available evidence on the effect of MRSA detection by rapid screening tests on hospital-acquired MRSA infections and acquisition rate. Eligible studies were retrieved from Medline, EmBase, Science Citation Index, and the Cochrane database. We judged as eligible those studies that compared hospitals and wards in which active screening for the detection of MRSA carriers was done at hospital admission by use of a rapid molecular test to those in which active screening was done with culture alone or not at all. To account for statistical heterogeneity between studies, random-effects models were used. Ten studies (nine interventional studies and one unblinded, cluster-randomised, crossover trial) were reviewed. Meta-analysis was done for studies reporting data on the same outcome. Primary outcomes included MRSA acquisition rate per 1000 patient-days (four studies); incidence of MRSA bloodstream infections per 1000 patient-days (three studies); and incidence of MRSA surgical-site infections per 100 surgical procedures (five studies). Compared with culture screening, use of rapid screening tests was not associated with a significant decrease in MRSA acquisition rate (risk ratio 0.87, 95% CI 0.61-1.24). Between wards applying rapid screening tests and those not applying screening, we noted a significantly decreased risk for MRSA bloodstream infections (0.54, 95% CI 0.41-0.71), but not for MRSA surgical-site infections (0.69, 95% CI 0.46-1.01). We conclude that active screening for MRSA is more important than the type of test used. Since important and costly decisions, such as mandatory legislation for MRSA universal screening, are under consideration in many countries worldwide, policy makers should be aware of the limits and the heterogeneity of the available evidence.

Vancomycin-resistant enterococci (VRE): transmission and control

Transmission of vancomycin-resistant enterococci (VRE) can occur through direct contact with colonised or infected patients or through indirect contact via the hands of health-care workers (HCWs), or via contaminated patient care equipment or environmental surfaces. Antibiotic exposure plays an important role in the transmission dynamic of VRE. Until now, the control measures aimed at reducing the incidence of VRE colonisation and infection in hospitals have included: education of HCWs with implementation of hand-washing practices and compliance; wide and targeted surveillance cultures; isolation of VRE-positive patients; pre-emptive isolation of high-risk patients; and restriction of antibiotic use. However, despite these, VRE is still endemic in many hospitals. The causes of this could be non-compliance with infection control interventions, overuse of antibiotics, and insensitive microbiological methods for detecting VRE in stool. A scoring system using point values has been demonstrated to be useful in reducing rates of nosocomial VRE colonisation. Future prospective comparative studies of infection control approaches in different epidemiological situations might be useful.

Antibiotic Usage and Risk of Colonization and Infection with Antibiotic-Resistant Bacteria: a Hospital Population-Based Study

ABSTRACT Accurate assessment of risk factors for nosocomial acquisition of colonization by antibiotic-resistant bacteria (ARB) is often confounded by scarce data on antibiotic use. A 12-month, nested, multicenter cohort study was conducted. Target ARB were methicillin (meticillin)-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and ciprofloxacin-resistant Pseudomonas aeruginosa (CR-PA). Nares and rectal swabs were obtained before and after starting antibiotics. Pulsed-field gel electrophoresis was done to define genetic relatedness of the strains. Primary outcomes were (i) the mean time, in days, for acquisition of target ARB colonization in patients previously not colonized; (ii) the rate of acquisition per 1,000 antibiotic-days according to different classes of antibiotics; (iii) the rate of infection caused by the same bacteria as those previously isolated in screening samples; and (iv) the risk factors for ARB acquisition. In total, 6,245 swabs from 864 inpatients were processed. The rate of acquisition was 3%, 2%, and 1% for MRSA, VRE, and CR-PA, respectively. The rate of acquisition of ARB per 1,000 antibiotic-days was 14 for carbapenems, 9 for glycopeptides, and 6 for broad-spectrum cephalosporins and quinolones. The highest rates of acquisition were observed for carbapenems in dialyzed and diabetic patients. Four risk factors were independently associated with acquisition of target ARB: use of carbapenems, age of >70 years, hospitalization for >16 days, and human immunodeficiency virus infection. During the 30-day follow-up, 4 among 42 patients newly colonized by ARB (9%) suffered from an infection due to the same bacteria as those isolated in a previous screening sample. Colonizing and infecting strains from single patients were genotypically identical. Identifying ARB colonization early during antibiotic therapy could target a high-risk hospitalized population that may benefit from intervention to decrease the risk of subsequent nosocomial infections.

Prosthetic joint infection: Recent developments in diagnosis and management

Over the past years there has been a significant increase in the number of joint prosthesis replacements worldwide. The most serious complication of joint prosthesis is infection with an incidence of 1.5-2.5% for primary interventions and up to 20% for revision procedures. The mortality rate ranges between 1% and nearly 3%. The economic cost of this complication is up to

Infection control and prevention measures to reduce the spread of vancomycin-resistant enterococci in hospitalized patients: a systematic review and meta-analysis

50,000 per patient and

In Vivo Emergence of Tigecycline Resistance in Multidrug-Resistant Klebsiella pneumoniae and Escherichia coli

250,000 million per year. A major issue in the management of prosthetic joint infection (PJI) is the relative difficulty in making a diagnosis so to cause a significant effect on the prognosis. Goals of the treatment are to eradicate infection, prevent its recurrence and preserve mechanical joint function. In this review we focus on the value of traditional and newer diagnostic tests and we discuss management and preventive strategies. European networks are needed to define the best diagnostic and treatment strategies in order to reduce future challenge posed by PJIs.

Epidemiology and genetic characteristics of extended-spectrum β-lactamase-producing Gram-negative bacteria causing urinary tract infections in long-term care facilities

OBJECTIVES Vancomycin-resistant enterococci (VRE) represent a major problem in healthcare settings worldwide. It is still unclear which is the most effective infection control and prevention (ICP) measure to reduce the spread of hospital-acquired VRE. METHODS Cochrane databases, MEDLINE, EMBASE and CINAHL were searched until June 2012 to find studies comparing wards/hospitals where ICP measures to prevent VRE transmission were investigated. In the absence of heterogeneity, a fixed-effects model was used to estimate the pooled risk ratio (RR). Study quality was assessed according to Cochrane Effective Practice and Organisation of Care (EPOC) criteria. RESULTS The search strategy retrieved 549 studies and 9 studies (1 randomized clinical trial, 3 controlled clinical trials and 5 interrupted time series) with 30, 949 participants were included. The overall study quality was low. Implementation of hand hygiene was associated with a 47% decrease in the VRE acquisition rate (pooled RR 0.53, 95% CI 0.39-0.73, I(2) 26%) while contact precautions did not significantly reduce the VRE acquisition rate (pooled RR 1.08, 95% CI 0.63-1.83, I(2) 0%). Due to the low number of studies, meta-analysis was not applied for surveillance screening, environmental cleaning and antibiotic formulary interventions. No studies were available on the effectiveness of isolation and cohorting of patients and staff. CONCLUSIONS Available evidence on the ICP measures to reduce VRE spread in adult hospitalized patients is poor. This systematic review suggests a significant role for the implementation of hand hygiene. Further studies with appropriate study design are urgently needed to define ICP measures able to reduce the acquisition of VRE among hospitalized patients.

Effect of highly active antiretroviral therapy on the incidence of bacterial pneumonia in HIV-infected subjects

ABSTRACT Although resistance to tigecycline has been reported in surveillance studies, very few reports have described the emergence of resistance in vivo. We report two cases of patients with infections due to SHV-12-producing Klebsiella pneumoniae and K. pneumoniae carbapenemase-3 (KPC-3)-producing Escherichia coli, which developed tigecycline resistance in vivo after treatment. The reported limited experience underlines the risk of occurrence of a tigecycline MIC increase under treatment pressure.

Prediction models to identify hospitalized patients at risk of being colonized or infected with multidrug-resistant Acinetobacter baumannii calcoaceticus complex

OBJECTIVES To assess risk factors for acquiring extended-spectrum β-lactamase-producing Gram-negative bacteria (ESBL+ GN) causing urinary tract infections (UTIs) in long-term care facilities (LTCFs). METHODS A prospective case-case-control study was carried out. In the first study, cases were defined as patients harbouring ESBL+ GN, while, in the second study, cases were defined as patients harbouring ESBL-negative (ESBL-) GN. Controls were selected by simple random sampling from patients without GN infection. ESBL determinants were characterized by hybridization, and confirmed by PCR and sequencing. RESULTS The study involved 297 LTCF patients (99 with ESBL+ GN UTI, 99 with ESBL- GN UTI and 99 without GN infection). ESBL+ GN UTIs were due to Escherichia coli (64%), Proteus mirabilis (25%) and Klebsiella pneumoniae (11%). The CTX-M-type enzymes were the most prevalent (73% of isolates), whereas TEM- and SHV-type ESBLs and AmpC-type enzymes were less prevalent (10%, 2% and 15% of isolates, respectively). Patients with ESBL+ GN UTI were more likely to have a permanent urinary catheter (OR 15, 95% CI 6.9-30.5) and to have received antimicrobial therapy in the previous 30 days (OR 4, 95% CI 1.2-10.9). After adjusting for type, dosage and duration of antibiotic, exposure to ≥7 days of quinolones and third-generation cephalosporins was associated with the highest risk of ESBL+ GN UTI development (OR 7, 95% CI 1.2-40). Independent risk factors for acquiring ESBL- GN UTIs were previous surgical procedures (OR 2, 95% CI 1.1-4) and the presence of a urinary catheter (OR 8, 95% CI 4-16). No specific antibiotics remained a significant risk for ESBL- GN UTI after adjusting for demographic and clinical risk factors. CONCLUSIONS Exposure to ≥7 days of quinolones and third-generation cephalosporins significantly increases the risk of ESBL+ GN UTI. Interventions aimed at improving compliance with antimicrobial stewardship principles should be further developed and implemented in LTCFs.