Céline Bourigault

Nosocomial outbreak of carbapenem-resistant Enterobacter cloacae highlighting the interspecies transferability of the blaOXA-48 gene in the gut flora

Sir, The emergence and dissemination of carbapenemases (KPC, VIM, IMP, NDM or OXA-48) among Enterobacteriaceae is a serious concern worldwide as it raises the problem of the lack of therapeutic options linked to frequent co-resistance. In November 2010, French guidelines were published to control the spread of carbapenemase-producing Enterobacteriaceae from patients repatriated and travellers hospitalized in French hospitals. However, we report the in vivo interspecies transferability of the OXA-48 carbapenemase by the investigation and management of a nosocomial outbreak in France. In April 2011, an elderly patient (Patient A) was transferred from Agadir (Morocco) to the internal medicine unit at Nantes University Hospital, France, for the treatment of a hip prosthetic joint infection. Upon admission, contact precautions were immediately adopted. A rectal swab inoculated on CHROMagarTM KPC medium (CHROMagar, Paris, France) revealed the gastrointestinal carriage of Enterobacter cloacae and Escherichia coli, both resistant to ertapenem and positive for blaOXA-48 by PCR. Therefore, a weekly colonization surveillance was performed on all patients hospitalized in the unit, and led to the discovery of OXA-48-producing E. cloacae in 3/54 patients (B, C and D) without recent history of travel. Furthermore, rectal swabs performed for Patients A and B found two OXA-48-producing Klebsiella pneumoniae isolates (Figure 1). The time between admission to the unit and the first positive culture varied between 3 and 16 days for the three secondary patients. However, Patient D, with a first negative screening, was transferred to the intensive care unit, and was detected as a carrier 3 days after re-admission to the internal medicine unit. We cannot exclude the possibility that this patient was colonized during the first stay in the internal medicine unit. OXA-48-producing E. cloacae isolates were detected intermittently in this patient (Figure 1). None of the four carriers developed infection. Active surveillance was continued until the last colonized patient was discharged. All isolates were resistant to ertapenem (range of MICs, 2 to ≥32 mg/L) and exhibited intermediate susceptibility or susceptibility to imipenem (range of MICs, 0.38–6 mg/L) and meropenem (range of MICs, 0.25–0.5 mg/L) according to the EUCAST guidelines 2011. Molecular testing showed that all E. cloacae isolates harboured the blaCTX-M-15 ESBL gene, while both E. coli and K. pneumoniae isolates were susceptible to third-generation cephalosporins and did not present any of the additional b-lactamases searched for (blaTEM, blaSHV apart from blaSHV-1, and blaCTX-M). The E. coli and K. pneumoniae isolates did not yield subcultures when plated on a CHROMagarTM ESBL medium (CHROMagar, Paris, France). Although other authors reported poor growth of E. coli strains, and underlined difficulties in differentiating colonies of E. cloacae and K. pneumoniae, in our experience the CHROMagarTM KPC medium was useful. The OXA-48 producing E. coli isolate from Patient A yielded a few small pink colonies, whereas the OXA-48producing K. pneumoniae isolate showed better growth, with large navy blue colonies easily distinguishable from the steel blue colonies of the OXA-48-producing E. cloacae isolate. All E. cloacae isolates showed indistinguishable PFGE patterns. According to PFGE and multilocus sequence typing (MLST; http://www.pasteur.fr/recherche/genopole/PF8/mlst/ Kpneumoniae.html) analyses, K. pneumoniae isolates were not clonally related [one new sequence type (ST) and one ST152]. The E. coli isolate belonged to ST38 (MLST, http://mlst.ucc.ie/ mlst/dbs/Ecoli). The blaOXA-48 gene was transferred by conjugation 4 to a rifampicin-resistant E. coli J53-2 from the E. cloacae, K. pneumoniae and E. coli isolates, while transfer of the blaCTX-M-15 gene from the E. cloacae isolates failed. Extraction of plasmids revealed that E. cloacae isolates carried two plasmids (60 and 165 kb), whereas E. coli, both K. pneumoniae isolates and all blaOXA-48-positive transconjugants carried a single plasmid that co-migrated with the 60 kb plasmid of E. cloacae isolates. The blaOXA-48 gene was part of the plasmid-borne Tn1999.2 transposon, since an insertion sequence IS1999 interrupted by an IS1R was detected by PCR mapping upstream of the blaOXA-48 gene. 2 This is the first report of a patient colonized with three enterobacterial isolates (E. cloacae, E. coli and K. pneumoniae) harbouring the blaOXA-48 gene. The emergence of this gene has been linked to the spread of a peculiar Tn1999-type transposon, but also to the dissemination of specific clones. Poirel et al. indicated that the same strain of OXA-48-producing E. coli, belonging to ST38, had been imported from Egypt and Turkey into France. In our study, Patient A carried an ST38-type E. coli, but the strain did not display an ESBL phenotype, as previously described. The discovery of the OXA-48 carbapenemase in several enterobacteria of the index case’s gastrointestinal flora rather suggested the possibility of an in vivo transfer of the OXA-48-encoding plasmid. This was confirmed by the isolation of another OXA-48-producing K. pneumoniae isolate in Patient B. In the gut, selection of resistant strains has been associated with a biological fitness cost and often reflects the impact of antimicrobial selection pressure. Previous exposure to fluoroquinolones or antipseudomonal penicillins has been described as a risk factor for acquisition of Research letters

Risk factors for mortality in patients with mediastinitis after cardiac surgery.

BACKGROUND Patients with mediastinitis after cardiac surgery have higher morbidity and mortality. AIMS Describe the characteristics of patients with mediastinitis, determine the mortality within one month, and assess the risk factors associated with mortality. METHODS Retrospective cohort study including all adult patients with mediastinitis during the 2002-2006 period at the Nantes University Hospital. Multivariate analysis by logistic regression and Kaplan-Meier curve of survey were done. RESULTS Nearly 5574 patients were operated during the study period, with a mediastinitis incidence rate of 0.7%, 28 patients (72%) had coronary artery bypass graft. The mortality rate increased from de 12.8% during hospital stay to 20.5% within one year. Only two deaths were associated with mediastinitis. The occurrence of a co-infection was the only independent risk factor associated with mortality (OR 13, P<0.04). The instantaneous risk of death was increased by 7 in patient with co-infection, particularly mechanical ventilator-associated pneumonia (CR 1,97). CONCLUSION Mortality varied according to the duration of surveillance, and mediastinitis was not the major cause of death. Mechanical ventilator-associated pneumonia after mediastinitis increases the mortality and needs specific prevention.

Prevention of healthcare-associated infections in neonates: room for improvement

Summary Infants in neonatal intensive care units (NICUs) are highly susceptible to infection due to the immaturity of their immune systems. Healthcare-associated infections (HCAIs) are associated with prolonged hospital stay, and represent a significant risk factor for neurological development problems and death. Improving HCAI control is a priority for NICUs. Many factors contribute to the occurrence of HCAIs in neonates such as poor hand hygiene, low nurse–infant ratios, environmental contamination and unnecessary use of antibiotics. Prevention is based on improving neonatal management, avoiding unnecessary use of central venous catheters, restricting use of antibiotics and H2 blockers, and introducing antifungal prophylaxis if necessary. Quality improvement interventions to reduce HCAIs in neonates seem to be the cornerstone of infection control.

Matching Bacteriological and Medico-Administrative Databases Is Efficient for a Computer-Enhanced Surveillance of Surgical Site Infections: Retrospective Analysis of 4,400 Surgical Procedures in a French University Hospital

OBJECTIVE Our goal was to estimate the performance statistics of an electronic surveillance system for surgical site infections (SSIs), generally applicable in French hospitals. METHODS Three detection algorithms using 2 different data sources were tested retrospectively on 9 types of surgical procedures performed between January 2010 and December 2011 in the University Hospital of Nantes. The first algorithm was based on administrative codes, the second was based on bacteriological data, and the third used both data sources. For each algorithm, sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated. The reference method was the hospitals routine surveillance: a comprehensive review of the computerized medical charts of the patients who underwent one of the targeted procedures during the study period. SETTING A 3,000-bed teaching hospital in western France. POPULATION We analyzed 4,400 targeted surgical procedures. RESULTS Sensitivity results varied significantly between the three algorithms, from 25% (95% confidence interval, 17-33) when using only administrative codes to 87% (80%-93%) with the bacteriological data and 90% (85%-96%) with the combined algorithm. Fewer variations were observed for specificity (91%-98%), PPV (21%-25%), and NPV (98% to nearly 100%). Overall, performance statistics were higher for deep SSIs than for superficial infections. CONCLUSIONS A reliable computer-enhanced SSI surveillance can easily be implemented in French hospitals using common data sources. This should allow infection control professionals to spend more time on prevention and education duties. However, a multicenter study should be conducted to assess the generalizability of this method.

Outbreak of Skin Infections Due to Panton-Valentine Leukocidin-Positive Methicillin-Susceptible Staphylococcus aureus in a French Prison in 2010-2011.

Background. An outbreak of PVL-positive MSSA skin and soft tissue-infections (SSTIs) was suspected in May 2010 when recurrent SSTI was diagnosed in an inmate of a large prison in Nantes, France. Methods and findings. Retrospective and prospective investigations were performed. Microbiological characterisation was by DNA microarray testing (S. aureus genotyping - Identibac, Alere). We identified 14 inmates meeting our clinical and microbiological case definition for PVL-MSSA SSTI between March 2010 and April 2011. The SSTIs developed in tattooed areas in 4 patients and in areas shaved daily with a mechanical razor in 4 other patients. All case isolates exhibited a similar SmaI pulsed-field gel electrophoresis pattern. Microarray analysis showed that all 14 isolates harboured genes encoding PVL and enterotoxins (A, H, K, and Q) and belonged to clonal complex 1 (CC1). Individual and collective hygiene measures, education delivered to inmates and prison employees, and antibiotic treatment of SSTIs were successful in controlling the outbreak. No new cases were identified after April 2011. Routine screening for PVL-positive MSSA carriage was not feasible. Conclusions. Our data suggest that tattooing and shaving with mechanical razors may constitute risk factors for SSTIs among previously colonised inmates and contribute to the PVL-MSSA outbreak in the prison. Allowing inmates access to professional tattooists and to the hygiene and safety conditions available to people in the community would help to prevent tattoo-related infections.

Outbreak caused by Proteus mirabilis isolates producing weakly expressed TEM-derived extended-spectrum β-lactamase in spinal cord injury patients with recurrent bacteriuria.

Abstract We performed a retrospective extended-spectrum β-lactamase (ESBL) molecular characterization of Proteus mirabilis isolates recovered from urine of spinal cord injury patients. A incorrectly detected TEM-24-producing clone and a new weakly expressed TEM-derived ESBL were discovered. In such patients, ESBL detection in daily practice should be improved by systematic use of a synergy test in strains of P. mirabilis resistant to penicillins.

Duodenoscopy: an amplifier of cross-transmission during a carbapenemase-producing Enterobacteriaceae outbreak in a gastroenterology pathway

Carbapenemase-producing Klebsiella pneumoniae (OXA-48 CPE) were identified in five patients who underwent an endoscopy with the same duodenoscope in October 2015. The endoscope was the only epidemiological link between these cases. A transient contamination of the duodenoscope following a failure in the disinfection process may have been the cause of transmission.

Clostridium difficile infections: analysis of recurrence in an area with low prevalence of 027 strain

I wish to comment on the opinion piece by Dancer et al. about centralization of microbiology laboratories, the thrust of which is that this necessarily threatens quality but does not save any money. While any such exercise can go wrong, I do not see much evidence for either of these positions, and having recently been through a similar exercise that has led to outsourcing of laboratory services from my employing organization to another provider, I feel qualified to comment. The real drivers of pathology consolidation in the National Health Service are that laboratory pathology has become more capital-intensive, while the employment costs of laboratory staff have risen, against a background of fiscal calamity and tariff deflation. Different disciplines are at different stages on that journey, but in microbiology the moves towards molecular testing and robotic processing contributes to an inexorable pressure to centralize. One day, everything might be done by perfectly accurate, self-QCing, idiot-proof near-patient tests (and we may have escaped our £1.5 trillion national debt), but at the present time the economic argument favours fewer, larger laboratories. Of course, the principles of good healthcare do not always align perfectly with the principles of good business. The downside of consolidation is as described by Dancer et al.; microbiologists cannot attend both the bench and the bedside so easily, the service is less flexible to local needs, and waiting-for-transport and in-transit times become significant components of the sample-to-report turnaround time. You either have a ‘hot-lab’, which is inefficient and difficult to manage, or you do not, which delays rapid turnaround tests such as cerebrospinal fluid microscopy. However, the upside is real. In our model, the combined workload now justifies extended weekend working and a night shift (which facilitates a move from batch to continuous processing), there is standardization across a wide geographical area and economies of scale mean that the service, as a whole, is saving money over and above the costs of investment in new technology. Furthermore, many of the cited disadvantages can be overcome provided there is a common information technology system and a commitment to good transport links before centralization.