E.G. Smyth

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.

The impact of blood culture reporting and clinical liaison on the empiric treatment of bacteraemia.

AIMS: To assess the impact of blood culture results and early clinical liaison on the treatment of patients with bacteraemia. METHODS: 123 patients with significant positive blood cultures were followed over a nine month period in a 620 bed teaching hospital. The impact of early blood culture reporting and clinical liaison on the cost and appropriateness of treatment was assessed. RESULTS: Empiric treatment was started before the Gram stain result in 107 (87%) patients. Treatment was altered on the basis of the Gram stain result in 39 (36%) of these patients, and on culture and sensitivity results in 53 (50%). The spectrum of antibiotic treatment was narrowed in 58 (54%) of these; 20 (19%) on Gram stain result alone. This resulted in a 42% reduction in daily antibiotic costs in patients who had received empiric treatment. Empiric treatment did not follow the hospital antibiotic policy in 49 (46%) of the patients treated. In patients where empiric treatment was not in accordance with hospital policy, 21 (44%) had an isolate resistant to the empiric treatment used; while in patients who received agents in accordance with hospital policy only one (1.7%) had a resistant isolate (p < 0.05). Patients who died (11 (9%)) were less likely to have received empiric treatment in accordance with the antibiotic policy, although this did not reach statistical significance (p = 0.1). CONCLUSION: Early reporting of Gram stain results from blood cultures, combined with early clinical liaison, results in more rational and cost effective treatment.

The effect of rapid screening for methicillin-resistant Staphylococcus aureus (MRSA) on the identification and earlier isolation of MRSA-positive patients.

OBJECTIVES (1) To determine whether rapid screening with polymerase chain reaction (PCR) assays leads to the earlier isolation of patients at risk for methicillin-resistant Staphylococcus aureus (MRSA) colonization, (2) to assess compliance with routine MRSA screening protocols, (3) to confirm the diagnostic accuracy of the Xpert MRSA real-time PCR assay (Cepheid) by comparison with culture, and (4) to compare turnaround times for PCR assay results with those for culture results. DESIGN Before-and-after study conducted in a 700-bed acute tertiary care referral hospital. Study periods were (1) a 5-week period before PCR testing began, (2) a 10-week period when the PCR assay was used, and (3) a 5-week period after PCR testing was discontinued. RESULTS Among 489 at-risk patients, MRSA was isolated from 20 (33%) of 60 patients during period 1, 77 (22%) of 349 patients during period 2, and 18 (23%) of 80 patients during period 3. Twenty-two (27%) of 82 at-risk patients were not screened during period 1, compared with 40 (10%) of 389 at-risk patients not screened during period 2 (P < .001). More MRSA-positive patients were preemptively isolated during periods 1 and 3 compared with period 2 (34 [24%] of 140 vs 28 [8%] of 389; P < .001); however, more MRSA-positive patients were isolated after notification of MRSA-positive results during period 2 (47 [13%] of 349) compared with periods 1 and 3 (2 [1%] of 140; P < .001). The sensitivity, specificity, positive predictive value, and negative predictive value of the PCR assay were 95%, 97%, 82%, and 99%, respectively. The mean turnaround time from receipt of specimens in the laboratory to PCR assay result was 2.6 hours. CONCLUSIONS Rapid screening with the Xpert MRSA PCR assay facilitated compliance with screening policies and the earlier isolation of MRSA-positive patients. Discrepant results confirm that PCR testing should be used as a screening tool rather than as a diagnostic tool.

Comparative activity of carbapenem testing: the COMPACT study

OBJECTIVES Doripenem is a new carbapenem recently introduced into Europe. The COMParative Activity of Carbapenem Testing (COMPACT) study compared the susceptibility of common Gram-negative bacilli causing serious infections in hospitalized patients with doripenem, imipenem and meropenem. METHODS Gram-negative isolates (4498 total: 2171 Pseudomonas species; 1910 Enterobacteriaceae; and 417 other Gram-negative bacilli) were collected from 80 centres in 16 countries in Europe, the Middle East and Africa during 2008-09. The MICs of doripenem, imipenem and meropenem were determined using Etest methodology and broth microdilution. Susceptibility was interpreted according to CLSI, EUCAST and FDA breakpoints. RESULTS The MIC(90)s of doripenem, imipenem and meropenem for all isolates were 8, ≥64 and 32 mg/L, respectively. Doripenem had the lowest MIC(90) for Pseudomonas species at 16 mg/L, with imipenem and meropenem values of ≥64 mg/L. Enterobacteriaceae were highly susceptible to all three carbapenems, with MIC(90)s of doripenem, imipenem and meropenem of 0.06, 0.5 and 0.12 mg/L, respectively. Other Gram-negative isolates, predominantly Acinetobacter baumannii, were resistant to all three carbapenems (MIC(90) ≥64 mg/L). Susceptibility to doripenem was observed in 14.9% of isolates resistant to imipenem and/or meropenem. CONCLUSIONS Doripenem showed excellent activity against Gram-negative isolates; generally it was more active than imipenem and at least as good as meropenem. Against Pseudomonas species, doripenem was more active than both imipenem and meropenem, with doripenem susceptibility observed for some imipenem- and/or meropenem-resistant isolates.

Emergence of MRSA in positive blood cultures from patients with febrile neutropenia—a cause for concern

Goals of workFebrile neutropenia (FN) causes considerable morbidity in patients on cytotoxic chemotherapy. Recently, there has been a trend towards fewer Gram-negative and more Gram-positive infections with increasing antibiotic resistance. To assess these patterns, data from a supra-regional cancer centre in Ireland were reviewed.Patients and methodsA 5-year review of all positive blood cultures in patients undergoing anti-cancer chemotherapy was carried out.Main resultsEight hundred and ninety-four patients were reviewed. The mean incidence of FN was 64.2 cases per year. Eight hundred and forty-six blood culture specimens were taken and 173 (20.4%) were culture positive. The isolated organisms were Gram positive (71.1%), Gram negative (27.8%) and fungal (1.1%). Of the Gram-positive organisms, 75.6% were staphylococci. Of these, 67.8% were coagulase-negative staphylococci and 30.1% were Staphylococci aureus. Amongst the S. aureus, 89.3% were methicillin-resistant (MRSA). Vancomycin-resistant enterococci were not identified as a cause of positive blood cultures.ConclusionsAmongst patients with cancer who develop FN in our hospital, Gram-positive bacteria account for the largest proportion. The high proportion of MRSA as a cause of positive blood cultures is of concern.

Community and hospital acquired Staphylococcus aureus septicaemia: 115 cases from a Dublin teaching hospital

Despite advances in diagnostic techniques and antimicrobials, septicaemia due to Staphylococcus aureus remains a common clinical problem with a significant mortality. We retrospectively compared community and hospital acquired cases of S. aureus septicaemia occurring in our 600 bed teaching hospital over a 30 month period. Of 110 episodes 32 (29%) were community acquired and 78 (71%) hospital acquired. A likely primary source was identified in 14 (44%) of community acquired cases and in 73 (94%) of hospital acquired cases. A secondary focus of infection was more common in community acquired cases (17, 53%) than hospital acquired cases (5, 6%). Mortality was significantly higher in community acquired cases (22% vs. 6%). An association was also found between the presence of endocarditis and increased mortality, although this did not reach significance. We also compared hospital acquired septicaemia due to methicillin sensitive and methicillin resistant S. aureus found a significantly higher mortality in the methicillin resistant group (22% vs. 3%, P < 0.05). S. aureus septicaemia remains an important cause of morbidity and mortality, particularly when associated with secondary foci of infection. This study also emphasises the importance of control of methicillin resistant strains in hospital.

Candida infection of the central nervous system following neurosurgery: a 12-year review

BackgroundCandida infection of the central nervous system (CNS) following neurosurgery is relatively unusual but is associated with significant morbidity and mortality. We present our experience with this infection in adults and discuss clinical characteristics, treatment options, and outcome.MethodsAll episodes of Candida isolated from the central nervous system were identified by searching our laboratory database. Review of the cases was performed by means of a retrospective chart review.ResultsEleven episodes of Candida CSF infection following neurosurgery were identified over a 12-year period. Candida albicans was the predominant species isolated (n = 8, 73%). All infections were associated with foreign intracranial material, nine with external ventricular drains (82%), one with a ventriculoperitoneal shunt, one with a lumbar drain, and one with Gliadel wafers (1,3-bis [2-chloroethyl]-1-nitrosurea). Fluconazole or liposomal amphotericin B were the most common anti-fungal agents used. The mortality rate identified in our series was 27%.ConclusionsCandida infection following neurosurgery remains a relatively rare occurrence but one that causes significant mortality. These are complex infections, the management of which benefits from a close liaison between the clinical microbiologist and neurosurgeon. Prompt initiation of antifungal agents and removal of infected devices offers the best hope of a cure.

Infection due to C. difficile ribotype 078: first report of cases in the Republic of Ireland

Clostridium difficile is an important healthcare-associated pathogen. Hypervirulent strains such as those belonging to ribotype 027 have been widely reported in recent years. A second strain associated with hypervirulence is ribotype 078 and the prevalence of Clostridium difficile infection (CDI) due to this ribotype appears to be increasing. This report describes an outbreak, in which 15cases of CDI due to ribotype 078 were detected in an Irish hospital and from a nursing home in the hospitals catchment area. C. difficile ribotype 078 accounted for 15% of total isolates submitted for ribotyping. The average age of patients with CDI due to ribotype 078 was 76 years. Forty-six percent of patients experienced recurrence of symptoms within eight weeks of diagnosis and CDI was felt to have directly contributed to five of the eight deaths. Use of enhanced DNA fingerprinting identified clusters within the 15 cases and suggested hitherto unrecognised links between some patients with CDI. Such approaches offer the promise to delineate common sources and transmission routes for C. difficile.

Evaluation of screening risk and nonrisk patients for methicillin-resistant Staphylococcus aureus on admission in an acute care hospital

BACKGROUND Screening for methicillin-resistant Staphylocccus aureus (MRSA) is advocated as part of control measures, but screening all patients on admission to hospital may not be cost-effective. OBJECTIVE Our objective was to evaluate the additional yield of screening all patients on admission compared with only patients with risk factors and to assess cost aspects. METHODS A prospective, nonrandomized observational study of screening nonrisk patients ≤72 hours of admission compared with only screening patients with risk factors over 3 years in a tertiary referral hospital was conducted. We also assessed the costs of screening both groups. RESULTS A total of 48 of 892 (5%) patients was MRSA positive; 28 of 314 (9%) during year 1, 12 of 257 (5%) during year 2, and 8 of 321 (2%) during year 3. There were significantly fewer MRSA-positive patients among nonrisk compared with MRSA-risk patients: 4 of 340 (1%) versus 44 of 552 (8%), P ≤ .0001, respectively. However, screening nonrisk patients increased the number of screening samples by 62% with a proportionate increase in the costs of screening. A backward stepwise logistic regression model identified age > 70 years, diagnosis of chronic pulmonary disease, previous MRSA infection, and admission to hospital during the previous 18 months as the most important independent predictors to discriminate between MRSA-positive and MRSA-negative patients on admission (94.3% accuracy, P < .001). CONCLUSION Screening patients without risk factors increased the number of screenings and costs but resulted in few additional cases being detected. In a hospital where MRSA is endemic, targeted screening of at-risk patients on admission remains the most efficient strategy for the early identification of MRSA-positive patients.