Elias Iosifidis

Bloodstream infections caused by metallo-β-lactamase/Klebsiella pneumoniae carbapenemase-producing K. pneumoniae among intensive care unit patients in Greece: risk factors for infection and impact of type of resistance on outcomes.

OBJECTIVE To determine risk factors for bloodstream infections (BSIs) caused by Klebsiella pneumoniae producing metallo-β-lactamases (MBLs) or K. pneumoniae carbapenemases (KPCs), as well as risk factors for mortality associated with carbapenem-resistant K. pneumoniae, among intensive care unit (ICU) patients. METHODS Two case-control studies were conducted in a patient cohort with K. pneumoniae BSIs in an 8-bed ICU in a Greek hospital from January 1, 2007, through December 31, 2008. In study 1, patients with K. pneumoniae BSIs were allocated among 3 groups according to isolate susceptibility profile: (1) carbapenem-susceptible insolates (control group), (2) MBL-producing isolates, or (3) KPC-producing isolates. The MBL and KPC groups were compared with the control group to identify risk factors for development of K. pneumoniae BSI. In study 2, patients with K. pneumoniae BSIs who died were compared with survivors to identify risk factors for mortality. RESULTS Fifty-nine patients had K. pneumoniae BSIs (22 with carbapenem-susceptible isolates, 18 with MBL-producing isolates, and 19 with KPC-producing isolates). All KPC-producing isolates carried the bla(KPC-2) gene, and 17 of 18 MBL-producing isolates carried bla(VIM-1). Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.13 [95% confidence interval, 1.03-1.25]; [Formula: see text]) was independently associated with KPC-producing K. pneumoniae BSIs. Nine (41%) of 22 control patients, 8 (44%) of 18 MBL group patients, and 13 (68%) of 19 KPC group patients died in the ICU. Nine (41%) of 22 control patients, 10 (56%) of 18 MBL group patients, and 15 (79%) of 19 KPC group patients died in the hospital. Isolation of KPC-producing K. pneumoniae was an independent predictor of ICU death ([Formula: see text]) and in-hospital death ([Formula: see text]) but not infection-attributable death. CONCLUSIONS BSIs due to KPC-producing K. pneumoniae resulted in significantly increased mortality. The accurate and rapid detection of these pathogens is necessary for therapeutic considerations and for the implementation of infection control measures to contain them.

Serum and Cerebrospinal Fluid Levels of Colistin in Pediatric Patients

ABSTRACT Using a liquid chromatography-tandem mass spectrometry method, the serum and cerebrospinal fluid (CSF) concentrations of colistin were determined in patients aged 1 months to 14 years receiving intravenous colistimethate sodium (60,000 to 225,000 IU/kg of body weight/day). Only in one of five courses studied (a 14-year-old receiving 225,000 IU/kg/day) did serum concentrations exceed the 2 μg/ml CLSI/EUCAST breakpoint defining susceptibility to colistin for Pseudomonas and Acinetobacter. CSF colistin concentrations were <0.2 μg/ml but increased in the presence of meningitis (∼0.5 μg/ml or 34 to 67% of serum levels).

Differential Correlation Between Rates of Antimicrobial Drug Consumption and Prevalence of Antimicrobial Resistance in a Tertiary Care Hospital in Greece

OBJECTIVE To investigate whether there is a correlation between the rates of antimicrobial drug consumption in hospital departments and the prevalence of antimicrobial resistance among clinically important bacteria recovered in the hospital. DESIGN Retrospective study. SETTING Tertiary care hospital in Greece. METHODS Data on antimicrobial consumption (from January 2001 through December 2004) were expressed as defined daily doses per 100 bed-days. The prevalence of antimicrobial resistance among isolates of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterococcus faecium recovered during the same time period were calculated by the microbiology department. We then performed the following analyses: (1) a comparison of the consumption rates for different antimicrobial groups in individual hospital departments, (2) a comparison of the prevalence of resistance to different antimicrobials, and (3) a correlation analysis of antimicrobial consumption rates and the prevalence of antimicrobial resistance. RESULTS The rates of antimicrobial consumption and the prevalence of resistance varied substantially among the hospitals departments. The annual rate of consumption for carbapenems correlated with the rate of consumption for glycopeptides and third-generation cephalosporins (P < .05). Among P. aeruginosa isolates, the prevalence of imipenem resistance correlated with the prevalence of resistance to amikacin, ciprofloxacin, and ceftazidime (P < .05). The rate of carbapenem consumption correlated with the prevalence of imipenem resistance among P. aeruginosa and A. baumannii isolates (P < .05). The rate of aminoglycoside consumption correlated with the prevalence of amikacin resistance among P. aeruginosa, K. pneumoniae, and E. coli isolates (P < .05). However, the rate of consumption for fluoroquinolones and glycopeptides had no correlation with the prevalence of ciprofloxacin resistance among gram-negative bacteria or vancomycin resistance among E. faecium isolates. CONCLUSIONS These data are suggestive of a differential relationship between antimicrobial consumption and the prevalence of antimicrobial resistance among various species and for various antimicrobial agents. These findings may help to optimize antimicrobial prescription policies in the hospital, especially in departments that have both high rates of antimicrobial consumption and a high prevalence of antimicrobial resistance.

Use of linezolid in pediatrics: a critical review.

BACKGROUND Linezolid, an oxazolidinone antibacterial agent, is available for intravenous/oral administration, with activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and penicillin-resistant Streptococcus pneumoniae (PRSP). These pathogens are important causes of hospital- and community-associated infections in children. METHODS PubMed was searched for all English language articles on patients younger than 18 years of age treated with linezolid, and an analysis of these articles was performed. RESULTS From the 133 articles retrieved, a total of 30 were studied (18 case reports, nine case series, and three clinical trials) based on the inclusion criteria preset for this review. In these articles, a total of 597 children received linezolid. MRSA was the most common pathogen, followed by VRE, PRSP, other bacteria and less common mycobacterial species. Linezolid was reported to be safe and effective for the treatment of pneumonia and endocarditis, as well as skin and soft tissue, central nervous system and osteoarticular infections. CONCLUSIONS Linezolid is promising as a safe and efficacious agent for the treatment of infections due to mainly resistant Gram-positive organisms in children who are unable to tolerate conventional agents or after treatment failure.

Vancomycin-resistant Enterococcus outbreak in a neonatal intensive care unit: Epidemiology, molecular analysis and risk factors

BACKGROUND Vancomycin-resistant Enterococcus faecium (VRE) may cause outbreaks in neonatal intensive care units (NICU). We describe a biphasic VRE outbreak and identify risk factors for VRE acquisition. METHODS After the occurrence of 2 cases of VRE infections in a 44-bed NICU, a bundle of interventions was implemented that included active surveillance cultures for VRE, enhanced infection control measures, and audits on antimicrobial use, from June to December 2008. Analysis was performed using polymerase chain reaction and pulse-field gel electrophoresis techniques. A case-control study was conducted to identify risk factors. RESULTS Among 253 neonates screened, 101 (39.9%) were found to be colonized with VRE. During the first 9 weeks of the study period, 59 new cases were detected. Molecular analysis showed 1 predominant clone. During weeks 10-12, no new cases of VRE colonization were detected; however, at week 13, just when the outbreak appeared to be over, a second wave occurred, with 42 new cases and multiple clones detected. Multivariate analysis identified administration of antimicrobial therapy for late-onset neonatal sepsis and hospitalization during the first month of this outbreak as significant risk factors for VRE colonization. CONCLUSION Both a high prevalence of VRE colonization and antimicrobial use promoted the transmission of VRE during this biphasic outbreak. Adherence to infection control measures and antimicrobial stewardship policies are of utmost importance.

Outcome of urinary tract infections caused by extended spectrum β-lactamase-producing Enterobacteriaceae in children.

The outcome of patients with urinary tract infections caused by extended spectrum &bgr;-lactamases (ESBL)-producing bacteria (cases) was compared with that of matched controls with urinary tract infections caused by non-extended spectrum &bgr;-lactamases-producing isolates. Significantly, more case patients received inappropriate empiric therapy than controls. Nevertheless, clinical and microbiologic outcomes as well as formation of renal scars did not differ between the 2 groups.

Advances in Antibacterial Therapy Against Emerging Bacterial Pathogens

During the last decade, both gram-positive and gram-negative bacteria that are resistant to most or all available antibacterial classes have become increasingly prevalent nosocomial pathogens, particularly among immunocompromised patients and those hospitalized in intensive care units. Among gram-positive bacteria, increasing concerns are posed for health care- and community-associated methicillin-resistant Staphylococcus aureus (MRSA), S aureus with reduced susceptibility to vancomycin, and vancomycin-resistant enterococci (VRE). A spectrum of newer antibacterial agents has been developed for the treatment of multi-resistant gram-positive bacteria, such as linezolid, tigecycline, daptomycin, and novel glycopeptides. Gram-negative bacteria have also developed multidrug resistance (MDR), which in the Enterobacteriacae is commonly due to the production of extended-spectrum beta-lactamases and carbapenemases of VIM, IMP, or KPC types. Currently, non-fermenting bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii are commonly resistant to all available antibiotics, including the newer agents. Colistin retains activity against most P aeruginosa and A baumannii, but its clinical use remains questionable, while newer carbapenems and tigecycline have limited additional advantages. Rational use of newer antibacterial agents coupled with enhanced infection control measures may be able to sufficiently control MDR organisms as to allow hematological patients to recover from serious infectious complications.

Frequency, clinical characteristics, and genotype distribution of rotavirus gastroenteritis in Greece (2007–2008)†‡

Rotavirus is the leading cause of acute gastroenteritis among young children worldwide. A prospective multi‐center study was conducted (2007–2008) in five Pediatric Hospitals to determine the prevalence, the clinical characteristics, and genotype distribution of rotavirus infection in Greece. Faecal samples were examined for the presence of group A rotavirus antigen by immunochromatography. Rotavirus strains were subjected to G and P genotyping by reverse‐transcriptase polymerase chain reaction (PCR) and sequencing. A total of 393 children (216 boys) of median age 23 months, participated in the study. Rotavirus was the cause of acute gastroenteritis in 166 children, 42.3% (CI 95%, 37.4–47.1%) of non‐hospitalized and 47.8% (CI 95%, 41.7–53.9%) of hospitalized patients. Rotavirus gastroenteritis occurred between December and April in 78.6% of the cases. Most children with RVG (77.8%) were between 3 months and 3 years old. The mean value of Clark severity score was 12.9 ± 5.1 for RVG and 10.5 ± 4.9 for non‐RVG (P < 0.01). Genotypes were determined in 117 strains and their distribution was as following: G1P[8], 49%; G2P[4], 31%; G4P[8], 10%; G9P[8], 9%; and G8P[14], 1%. In conclusion, rotavirus is a frequent cause of acute gastroenteritis in Greece. The genotypes circulating are similar with those of other European countries. J. Med. Virol. 83:165–169, 2011.

Daptomycin use in a neonate: serum level monitoring and outcome.

We present a case of successfully treated persistent bacteremia due to Gram-positive bacteria with daptomycin in a preterm neonate. Daptomycin was given at higher doses (6 mg/kg/dose) and shorter intervals (every 12 hours) than those recommended for adults with no adverse events. Peak and trough serum concentrations of daptomycin were 27.3 and 11.6 μg/mL [DOSAGE ERROR CORRECTED] at day 4 as well as 22.9 and 7.9 μg/mL [DOSAGE ERROR CORRECTED]at day 11 after initiation of treatment, respectively.

Molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae in Greece

Hospital infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) constitute a worldwide problem associated with high rates of treatment failure and mortality. In Greece, CRKP have emerged in 2002 due to VIM carbapenemase production and later due to KPC, NDM and OXA-48-like carbapenemases that have become endemic. The molecular epidemiology of CRKP strains is dynamic, as antibiotic consumption and worldwide traveling are strongly associated with global spread of CRKP isolates. Lately, porin defects, such as disruption of OmpK35 and production of OmpK36 variant, have also contributed to carbapenem resistance. In the coming years, the high prevalence of CRKP will require intense infection control measures, while novel molecular patterns may appear. To our knowledge, this is the first review analyzing the molecular epidemiology of CRKP strains in Greece.