Smilja Kalenić

Clinical Impact of Antimicrobial Resistance in European Hospitals: Excess Mortality and Length of Hospital Stay Related to Methicillin-Resistant Staphylococcus aureus Bloodstream Infections

ABSTRACT Antimicrobial resistance is threatening the successful management of nosocomial infections worldwide. Despite the therapeutic limitations imposed by methicillin-resistant Staphylococcus aureus (MRSA), its clinical impact is still debated. The objective of this study was to estimate the excess mortality and length of hospital stay (LOS) associated with MRSA bloodstream infections (BSI) in European hospitals. Between July 2007 and June 2008, a multicenter, prospective, parallel matched-cohort study was carried out in 13 tertiary care hospitals in as many European countries. Cohort I consisted of patients with MRSA BSI and cohort II of patients with methicillin-susceptible S. aureus (MSSA) BSI. The patients in both cohorts were matched for LOS prior to the onset of BSI with patients free of the respective BSI. Cohort I consisted of 248 MRSA patients and 453 controls and cohort II of 618 MSSA patients and 1,170 controls. Compared to the controls, MRSA patients had higher 30-day mortality (adjusted odds ratio [aOR] = 4.4) and higher hospital mortality (adjusted hazard ratio [aHR] = 3.5). Their excess LOS was 9.2 days. MSSA patients also had higher 30-day (aOR = 2.4) and hospital (aHR = 3.1) mortality and an excess LOS of 8.6 days. When the outcomes from the two cohorts were compared, an effect attributable to methicillin resistance was found for 30-day mortality (OR = 1.8; P = 0.04), but not for hospital mortality (HR = 1.1; P = 0.63) or LOS (difference = 0.6 days; P = 0.96). Irrespective of methicillin susceptibility, S. aureus BSI has a significant impact on morbidity and mortality. In addition, MRSA BSI leads to a fatal outcome more frequently than MSSA BSI. Infection control efforts in hospitals should aim to contain infections caused by both resistant and susceptible S. aureus.

Burden of antimicrobial resistance in European hospitals: excess mortality and length of hospital stay associated with bloodstream infections due to Escherichia coli resistant to third-generation cephalosporins

OBJECTIVES This study determined excess mortality and length of hospital stay (LOS) attributable to bloodstream infection (BSI) caused by third-generation-cephalosporin-resistant Escherichia coli in Europe. METHODS A prospective parallel matched cohort design was used. Cohort I consisted of patients with third-generation-cephalosporin-resistant E. coli BSI (REC) and cohort II consisted of patients with third-generation-cephalosporin-susceptible E. coli BSI (SEC). Patients in both cohorts were matched for LOS before infection with patients free of the respective BSI. Thirteen European tertiary care centres participated between July 2007 and June 2008. RESULTS Cohort I consisted of 111 REC patients and 204 controls and cohort II consisted of 1110 SEC patients and 2084 controls. REC patients had a higher mortality at 30 days (adjusted odds ratio = 4.6) and a higher hospital mortality (adjusted hazard ratio = 5.7) than their controls. LOS was increased by 8 days. For SEC patients, these figures were adjusted odds ratio = 1.9, adjusted hazard ratio = 2.0 and excess LOS = 3 days. A 2.5 times [95% confidence interval (95% CI) 0.9-6.8] increase in all-cause mortality at 30 days and a 2.9 times (95% CI 1.2-6.9) increase in mortality during entire hospital stay as well as an excess LOS of 5 days (95% CI 0.4-10.2) could be attributed to resistance to third-generation cephalosporins in E. coli BSI. CONCLUSIONS Morbidity and mortality attributable to third-generation-cephalosporin-resistant E. coli BSI is significant. If prevailing resistance trends continue, high societal and economic costs can be expected. Better management of infections caused by resistant E. coli is becoming essential.

P171: Promoting European infection control / hospital hygiene core competencies (EIC/HHCC): a comparative analysis with related disciplines

Training Infection Control in Europe (TRICE) in 2010 identified significant differences within European Countries (EC) in the existence of Infection Control /Hospital Hygiene (IC/HH) courses and their compliance with the Improving Patient Safety in Europe (IPSE, 2008) recommended Core Competencies. The need to improve official recognition of “IC/HH degrees” for healthcare professionals also emerged. TRICE further developed, agreed EIC/HHCC with two tiers, published by ECDC in March 2013 as a Technical Document.

Surveillance of microbial resistance in European Intensive Care Units: a first report from the Care-ICU programme for improved infection control

PurposeTo report initial results from a European ICU surveillance programme focussing on antibiotic consumption, microbial resistance and infection control.MethodsThirty-five ICUs participated during 2005. Microbial resistance, antibiotic consumption and infection control stewardship measures were entered locally into a web-application. Results were validated locally, aggregated by project leaders and fed back to support local audit and benchmarking.ResultsMedian (range) antibiotic consumption was 1,254 (range 348–4,992) DDD per 1,000 occupied bed days. The proportion of MRSA was median 11.6% (range 0–100), for ESBL phenotype of E. coli and K. pneumoniae 3.9% (0–80) and 14.3% (0–77.8) respectively, and for carbapenem-resistant P. aeruginosa 22.5% (0–100). Screening on admission for alert pathogens was commonly omitted, and there was a lack of single rooms for isolation.ConclusionsThe surveillance programme demonstrated wide variation in antibiotic consumption, microbial resistance and infection control measures. The programme may, by providing rapid access to aggregated results, promote local and regional audit and benchmarking of antibiotic use and infection control practices.

Helicobacter pylori Eradication Therapy Success Regarding Different Treatment Period Based on Clarithromycin or Metronidazole Triple-Therapy Regimens

Background: The study compares the eradication success of standard first‐line triple therapies of different durations (7, 10, and 14 days).

Are there regional variations in the diagnosis surveillance, and control of methicillin-resistant Staphylococcus aureus?

OBJECTIVE To assess the way healthcare facilities (HCFs) diagnose, survey, and control methicillin-resistant Staphylococcus aureus (MRSA). DESIGN Questionnaire. SETTING Ninety HCFs in 30 countries. RESULTS Evaluation of susceptibility testing methods showed that 8 laboratories (9%) used oxacillin disks with antimicrobial content different from the one recommended, 12 (13%) did not determine MRSA susceptibility to vancomycin, and 4 (4.5%) reported instances of isolation of vancomycin-resistant S. aureus but neither confirmed this resistance nor alerted public health authorities. A MRSA control program was reported by 55 (61.1%) of the HCFs. The following isolation precautions were routinely used: hospitalization in a private room (34.4%), wearing of gloves (62.2%), wearing of gowns (44.4%), hand washing by healthcare workers (53.3%), use of an isolation sign on the patients door (43%), or all four. When the characteristics of HCFs with low incidence rates (< 0.4 per 1,000 patient-days) were compared with those of HCFs with high incidence rates (> or = 0.4 per 1,000 patient-days), having a higher mean number of beds per infection control nurse was the only factor significantly associated with HCFs with high incidence rates (834 vs 318 beds; P = .02). CONCLUSION Our results emphasize the urgent need to strengthen the microbiologic and epidemiologic capacities of HCFs worldwide to prevent MRSA transmission and to prepare them to address the possible emergence of vancomycin-resistant S. aureus.

NDM-1-producing Klebsiella pneumoniae, Croatia.

To the Editor: The novel metallo-β-lactamase named New Delhi metallo-β-lactamase (NDM-1) was identified from Klebsiella pneumoniae and Escherichia coli isolates in Sweden from a patient previously hospitalized in India (1). NDM-1 is spreading rapidly worldwide to nonclonally related isolates, many of which are directly or indirectly tracked to the Indian subcontinent (2). A carbapenem-resistant K. pneumoniae strain, KLZA, was isolated in May 2009 from the culture of a blood sample from of a 40-year-old man on the day after his admission to a surgical intensive care unit of the Clinical Hospital Center in Zagreb, Croatia. The patient had been transferred after 5 days of hospitalization in Bosnia and Herzegovina following a car accident. The clinical history mentioned antimicrobial drug treatment that did not include carbapenems (gentamicin, metronidazole, and ceftriaxone) and no link to the Indian subcontinent. Antimicrobial drug susceptibility testing was performed by Vitek2 (bioMerieux, Marcy-l’Etoile, France) and broth microdilution and interpreted according to the latest documents from the European Committee on Antimicrobial Susceptibility Testing (www.eucast.org/clinical_breakpoints/, version 1.1). The strain proved resistant to imipenem and meropenem, to all broad-spectrum cephalosporins, and to aminoglycosides and susceptible to ciprofloxacin and tigecycline (Table). We checked for blaVIM, blaIMP, blaSPM, blaGIM, blaSIM, and blaNDM resistance genes by using PCR. A PCR product was obtained only with the NDM primers, after being purified (QIAquick PCR Purification Kit, QIAGEN, Hilden, Germany), its sequence showed 100% identity with blaNDM-1. Table MIC of the KLZA strain of Klebsiella pneumoniae and its transconjugant and recipient Strain genotyping was performed by multilocus sequence typing to determine the sequence type (ST) of the isolate and to establish a comparison with previously reported NDM-1–producing isolates. Allelic numbers were obtained on the basis of sequences of 7 housekeeping genes at www.pasteur.fr/recherche/genopole/PF8/mlst/Kpneumoniae.html. Multilocus sequence typing identified K. pneumoniae KLZA as an ST25 strain, which significantly differs from the ST14 type found in the index NDM-1–producing strain and from other isolates originating from India (1) and then in other countries. ST25 K. pneumoniae was also found in K. pneumoniae isolates in Geneva (3). Other K. pneumoniae STs harboring NDM-1 were ST15, ST16, and ST147 (4–7). Resistance was transferred by conjugation to E. coli J53, with selection based on growth on agar in the presence of ceftazidime (10 mg/L) and azide (100 mg/L). The conjugant T1 showed resistance to β-lactams, including all carbapenems, as well as decreased susceptibility to ciprofloxacin. The KLZA strain and its transconjugant harbored other determinant of resistance, namely blaCTX-M-15, blaCMY-16, and qnrA6. Plasmid incompatibility groups, determined by a PCR-based replicon typing method, belonged to the incA/C replicon type. This report of an NDM-1–producing K. pneumoniae in Croatia adds to those of other cases in patients from patients hospitalized in the Balkan area. The patient in this report had no apparent link to the Indian subcontinent. In a survey conducted by the European Centre for Disease Prevention and Control to gather information about the spread of NDM-1–producing Enterobacteriaceae in Europe and reporting cases from 13 countries during 2008–2010, five of the 55 persons with known travel histories had traveled to the Balkan region during the month before diagnosis of their infection: 2 to Kosovo and 1 each to Serbia, Montenegro, and Bosnia and Herzegovina. All had received hospital care in Balkan countries because of an illness or accident that occurred during the journey (7). Two of the latter cases (4,8) and a case from Germany (9) were subsequently published. No patient had any apparent link to the Indian subcontinent. Although the way NDM-1 isolates might have been imported to western Europe not only from the Indian subcontinent but also from Balkan countries (10) has been highlighted, awareness of western Europe as a possible area of endemicity remains limited. The aforementioned report from Germany, although recognizing that the patient had been repatriated after hospitalization in Serbia, declared “no evidence about contact with people from regions where NDM-enterobacteria are endemic” (9). This limited awareness shows the threat of neglecting to screen patients who are transferred from countries thought not to be at risk for NDM-1. Furthermore, it means that specimen are not sent to the local reference laboratories and recognized as positive for NDM-1, thus permitting wide dissemination of NDM-1–producing enterobacteria in the community (4). The accumulating evidence of NDM-1 from the Balkan area could suggest a possible multifocal spread of this enzyme, with the Balkans as a possible second area of endemicity, in addition to the Indian subcontinent, and prompts for widespread epidemiologic surveillance.

Impact of ampicillin and cefuroxime on bacterial colonization and infection in patients on a neonatal intensive care unit

The impact of ampicillin and cefuroxime on the bacterial flora of neonates was examined in a neonatal intensive care unit (NICU). For the first period of study (January-September 1989), ampicillin plus gentamicin were used as empirical therapy of infection. During this time, 92.6% of all Gram-negative bacilli (GNB) were resistant to ampicillin and 56.6% to cefuroxime. These percentages decreased significantly (P < 0.05) to 60.0% and 16.2% respectively, over the next period of study (October 1989-October 1990) when cefuroxime+gentamicin were used. A decrease in the number of cases of GNB from bacteraemia and meningitis was also significant (from 21.2% to 11.2%), and this correlated with a decline in the occurrence of Klebsiella pneumoniae. However, the number of enterococcal isolates and cases of enterococcal bacteraemia increased. These observations underline the important effect of ampicillin and cefuroxime in modulating the bacterial flora and its antibiotic resistance in patients on a NICU.

A variant of the Southern German clone of methicillin-resistant Staphylococcus aureus is predominant in Croatia

The aim of the present study was to investigate the antibiotic susceptibility patterns and molecular epidemiology of clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered in 24 hospitals in 20 cities in Croatia from October to December 2004. A total of 1815 consecutive S. aureus isolates were recovered, 248 of which were MRSA. The MRSA isolates were analysed using spa typing, multilocus sequence typing and SCCmec typing. Furthermore, the presence of Panton-Valentine leukocidin (PVL) genes was determined as a genetic marker for community-associated MRSA. The MRSA prevalence was 14%. Ninety-six per cent of the MRSA isolates were resistant to ciprofloxacin, 95% to clindamycin and azithromycin, 94% to gentamicin, and 93% to erythromycin. The majority of the MRSA isolates (78%) was associated with the ST111-MRSA-I clone. In addition, various other endemic MRSA clones were observed, such as the ST247-MRSA-I (4%), the ST45-MRSA-IV (2%), the ST5-MRSA-I (2%), the ST239-MRSA-III (2%), the ST5-MRSA-II (1%), the ST8-MRSA-IV (1%) and the ST5-MRSA-IV (<1%) clones. Furthermore, we observed one PVL-negative ST80-MRSA-IV isolate. Four PVL-positive MRSA isolates were found, associated with ST8-MRSA-IV, ST80-MRSA-IV and ST80-MRSA-I. The ST111-MRSA-I clone was predominant in Croatia. Future surveillance studies of MRSA are important to elucidate whether changes in the clonal distribution of MRSA will occur, and if the minor endemic MRSA clones observed in the present study will replace the ST111-MRSA-I clone on a large scale.

Coronal Microleakage of Two Root-end Filling Materials Using a Polymicrobial Marker

The purpose of this study was to evaluate polymicrobial coronal leakage of mineral trioxide aggregate (MTA) and amalgam. There were 108 single-rooted teeth randomly divided into 3 groups of 32 teeth each and positive and negative control groups of 6 teeth and obturated with gutta percha and either Diaket (3M/ESPE, Seefeld, Germany), AH Plus (Dentsply, De Trey, Konstanz, Germany), or Ketac Endo (3M/ESPE). These groups were further divided into 2 subgroups of 16 teeth in which root ends were resected and obturated with either MTA or zinc-free amalgam. The samples have been incorporated in a dual-chamber leakage model with a polymicrobial marker of five facultative anaerobes on the coronal part. Leakage was observing during a period of 90 days. The least leakage was found in a combination of Diaket and MTA (76.9 +/-14.8 days) followed by AH Plus and MTA (66.1 +/- 18.7), Diaket and amalgam (60.0 +/- 23.1), AH Plus and amalgam (56.9 +/- 22.1), and Ketac Endo and MTA (42.1 +/- 17.8), whereas the greatest leakage was observed in the Ketac Endo and amalgam group (40.0 +/- 17.24). Samples filled with MTA showed significantly better sealing than samples filled with amalgam (p < 0.05).