Ashley Querry

Co-production of NDM-1 and OXA-232 by Klebsiella pneumoniae.

To the Editor: New Delhi metallo-β-lactamase 1 (NDM-1) and OXA-48-group β-lactamase have been increasingly reported as carbapenemases responsible for carbapenem resistance in Enterobacteriaceae worldwide (1). However, in the United States, Klebsiella pneumoniae carbapenemase (KPC)–type β-lactamase is the most common carbapenemase among Enterobacteriaceae, especially K. pneumoniae. Isolates producing NDM-1 were first reported in the United States in 2010 (2), followed by several case reports and most recently a hospital outbreak in Colorado (3–6). As for OXA-48-group β-lactamase, 2 cases of infection with OXA-48–producing K. pneumoniae were recently reported from Virginia (7). We report K. pneumoniae co-producing NDM-1 and OXA-232, a variant of OXA-48, and Escherichia coli producing NDM-1 that were isolated from the same patient. A 69-year-old woman was hospitalized in India for subarachnoid hemorrhage in January 2013. Her hospitalization was complicated by unsuccessful coil embolization and subsequent hydrocephalus. A ventriculoperitoneal shunt was inserted, and she was transferred to an acute care hospital in Pittsburgh, Pennsylvania, USA, for further management in February 2013. She underwent reinsertion of the shunt and was discharged to a long-term care facility (LTCF 1). She was readmitted to the same hospital because of fever in March 2013. A urine culture collected at the time of readmission grew carbapenem-resistant K. pneumoniae and extended-spectrum β-lactamase–producing E. coli. Although production of KPC-type β-lactamase was initially suspected in K. pneumoniae, the unusually high level of resistance to amikacin (MIC >32 μg/mL) and gentamicin (MIC >8 μg/mL) increased concern for presence of an NDM-1 producer, which is frequently highly resistant to aminoglycosides because of production of 16S rRNA methyltransferase (8). A modified Hodge test showed a positive result for carbapenemase production, and a metallo-β-lactamase Etest (bioMerieux, Marcy l’Etoile, France) showed a positive result for metallo-β-lactamase production. PCR and sequencing identified NDM-1 and OXA-232, a 5-aa variant of OXA-48 recently reported in K. pneumoniae isolates from India (9). Presence of the gene for 16S rRNA methyltransferase (armA) was also confirmed by PCR and sequencing and accounted for the high-level aminoglycoside resistance. The isolate belonged to sequence type (ST) 14, as determined by multilocus sequence typing, and has been reported to be common among NDM-1–producing K. pneumoniae in Europe (10). The patient was discharged to LTCF 1 but was readmitted because of recurrent fever. A urine culture collected at this admission grew carbapenem-resistant K. pneumoniae and carbapenem-resistant E. coli. This E. coli isolate belonged to ST95 and was positive for the NDM-1 gene but negative for the OXA-48 group and armA genes. The original extended-spectrum β-lactamase–producing E. coli isolate belonged to ST3865, which is distinct from ST95. Therefore, it is likely that the patient was already colonized by NDM-1–producing E. coli ST95 at the time of the first admission, but this colonization was not detected in a clinical culture at that time. All K. pneumoniae and E. coli isolates remained susceptible to fosfomycin and colistin. The patient did not receive any antimicrobial drug therapy specific for these isolates because she was deemed to be only colonized with them in the urine. Enhanced contact precautions were also implemented at the time of PCR confirmation of the NDM-1 gene. These precautions included all components of contact precautions (handwashing, gowns, gloves, disinfected/dedicated equipment), and dedicated personnel monitored compliance with these measures around the clock. The patient was eventually discharged to another long-term care facility (LTCF 2) in April 2013. A point surveillance testing for NDM-1–producing Enterobacteriaceae by using rectal swab specimens was conducted for all inpatients at the acute-care hospital and for all residents of the unit at LTCF 2. Testing did not identify any other patients colonized with NDM-1–producing Enterobacteriaceae. In transformation and conjugation experiments, transformants carrying the OXA-232 gene were obtained from K. pneumoniae, but those carrying the NDM-1 gene could not be obtained by either method, suggesting that the 2 genes were not located on the same plasmid. For E. coli, transformants and transconjugants carrying the NDM-1 gene were obtained, which indicated that this gene was located on a self-conjugative plasmid. Detection of NDM-1– or OXA-48-group–producing Enterobacteriaceae, in particular K. pneumoniae, poses a diagnostic challenge in regions to which KPC-producing K. pneumoniae is endemic. In our case, recognition of resistance to multiple aminoglycosides by an automated instrument, which was confirmed to be high level by the disk diffusion method (i.e., no inhibition zone), prompted early detection and implementation of appropriate infection prevention measures. Production of 16S rRNA methyltransferase by KPC-producing K. pneumoniae is extremely rare, and no cases have been identified in the United States. Therefore, we propose that high-level resistance to amikacin and gentamicin can serve as a clue for suspecting potential NDM-1–producing isolates in clinical diagnostic laboratories. Conversely, Enterobacteriaceae producing OXA-48-group carbapenemase, including variants such as OXA-232, do not have characteristic susceptibility patterns and may easily not be recognized in areas with a high background prevalence of KPC-producing organisms. Therefore, organisms producing OXA-48 or their variants might have already spread in the United States.

Genomic Epidemiology of an Endoscope-Associated Outbreak of Klebsiella pneumoniae Carbapenemase (KPC)-Producing K. pneumoniae.

Increased incidence of infections due to Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) was noted among patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) at a single hospital. An epidemiologic investigation identified KPC-Kp and non-KPC-producing, extended-spectrum β-lactamase (ESBL)-producing Kp in cultures from 2 endoscopes. Genotyping was performed on patient and endoscope isolates to characterize the microbial genomics of the outbreak. Genetic similarity of 51 Kp isolates from 37 patients and 3 endoscopes was assessed by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Five patient and 2 endoscope isolates underwent whole genome sequencing (WGS). Two KPC-encoding plasmids were characterized by single molecule, real-time sequencing. Plasmid diversity was assessed by endonuclease digestion. Genomic and epidemiologic data were used in conjunction to investigate the outbreak source. Two clusters of Kp patient isolates were genetically related to endoscope isolates by PFGE. A subset of patient isolates were collected post-ERCP, suggesting ERCP endoscopes as a possible source. A phylogeny of 7 Kp genomes from patient and endoscope isolates supported ERCP as a potential source of transmission. Differences in gene content defined 5 ST258 subclades and identified 2 of the subclades as outbreak-associated. A novel KPC-encoding plasmid, pKp28 helped define and track one endoscope-associated ST258 subclade. WGS demonstrated high genetic relatedness of patient and ERCP endoscope isolates suggesting ERCP-associated transmission of ST258 KPC-Kp. Gene and plasmid content discriminated the outbreak from endemic ST258 populations and assisted with the molecular epidemiologic investigation of an extended KPC-Kp outbreak.

Clinical Appraisal of Fosfomycin in the Era of Antimicrobial Resistance

ABSTRACT Fosfomycin is recommended as one of the first-line agents for treatment of urinary tract infections (UTIs) in the latest guidelines endorsed by the Infectious Diseases Society of America (IDSA) and the European Society for Clinical Microbiology and Infectious Diseases (ESCMID). We evaluated the use of fosfomycin among inpatients at a tertiary care hospital between 2009 and 2013. UTI cases were defined using physician diagnosis and the National Healthcare Safety Network (NHSN) surveillance definitions. The number of patients treated with fosfomycin increased from none in 2009 to 391 in 2013. Among 537 patients who received fosfomycin for any indication during this period, UTI was the most common indication (74%), followed by asymptomatic bacteriuria (10%). All except 19 patients received a single dose of fosfomycin. Escherichia coli was the most common organism involved (52%). For 119 patients with UTIs, after exclusion of those with negative urine culture results, negative urinalysis results, receipt of additional agents, or indeterminate clinical outcomes, the clinical success rate at 48 h was 74.8%. Of 89 patients who met the criteria for NHSN-defined UTIs, 89.9% had successful outcomes. Recurrent infections occurred in 4.3% of cases, and mild adverse events were observed in 2.0%. All 100 randomly selected extended-spectrum β-lactamase (ESBL)-producing E. coli clinical isolates from this period were susceptible to fosfomycin. In conclusion, the use of fosfomycin has increased substantially since implementation of the updated guidelines at this hospital. Fosfomycin was used mainly for the treatment of physician-diagnosed UTIs, and the clinical outcomes were generally favorable. Fosfomycin maintained activity against E. coli despite the increased use of the agent.

Risk Factors for Surgical Site Infections Following Neurosurgical Spinal Fusion Operations: A Case Control Study

OBJECTIVE To determine risk factors for the development of surgical site infections (SSIs) in neurosurgery patients undergoing spinal fusion. DESIGN Retrospective case-control study. SETTING Large, academic, quaternary care center. PATIENTS The study population included all neurosurgery patients who underwent spinal fusion between August 1, 2009, and August 31, 2013. Cases were defined as patients in the study cohort who developed an SSI. Controls were patients in the study cohort who did not develop an SSI. METHODS To achieve 80% power with an ability to detect an odds ratio (OR) of 2, we performed an unmatched case-control study with equal numbers of cases and controls. RESULTS During the study period, 5,473 spinal fusion procedures were performed by neurosurgeons in our hospital. With 161 SSIs recorded during the study period, the incidence of SSIs associated with these procedures was 2.94%. While anterior surgical approach was found to be a protective factor (OR, 0.20; 95% confidence interval [CI], 0.08-0.52), duration of procedure (OR, 1.58; 95% CI, 1.29-1.93), American Society of Anesthesiologists score of 3 or 4 (OR, 1.79; 95% CI, 1.00-3.18), and hospitalization within the prior 30 days (OR, 5.8; 95% CI, 1.37-24.57) were found in multivariate analysis to be independent predictors of SSI following spinal fusion. Prior methicillin-resistant Staphylococcus aureus (MRSA) nares colonization was highly associated with odds 20 times higher of SSI following spinal fusion (OR, 20.30; 95% CI, 4.64-8.78). CONCLUSIONS In additional to nonmodifiable risk factors, prior colonization with MRSA is a modifiable risk factor very strongly associated with development of SSI following spinal fusion. Infect Control Hosp Epidemiol 2017;38:348-352.

Draft Genome Sequences of Four Hospital-Associated Pseudomonas putida Isolates

ABSTRACT We present here the draft genome sequences of four Pseudomonas putida isolates belonging to a single clone suspected for nosocomial transmission between patients and a bronchoscope in a tertiary hospital. The four genome sequences belong to a single lineage but contain differences in their mobile genetic elements.

Reducing Surgical Infections and Implant Costs via a Novel Paradigm of Enhanced Physician Awareness

BACKGROUND Studies have demonstrated that physicians are often unaware of prescription drug, laboratory, diagnostic, and surgical supply costs. OBJECTIVE To investigate the effects of increased physician awareness on infection incidence and surgical device cost containment. METHODS Within our institution, physicians were informed of individual, independently adjudicated, craniotomy and ventricular shunt infection incidence and rankings among peers, after which a protocol aimed at reducing skin bacterial burden was implemented for craniotomies. Physicians were also made aware of the costs for shunts and dural substitutes as well as available alternatives. RESULTS The combined craniotomy and ventricular shunt infection incidence significantly decreased by 37.5% from 3.2% over May 2011 to April 2015 (132 infections/4137 procedures) to 2.1% over May 2015 to April 2016 (26 infections/1250 procedures; P = .041). The average annual cost savings was

Implementation of an infection prevention bundle and increased physician awareness improves surgical outcomes and reduces costs associated with spine surgery

234 175 from preventing postoperative craniotomy infections and

Times Up! Manually Working to Remove Patients from Methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant Enterococcus faecium (VRE) Isolation Precautions

121 125 from preventing postoperative ventricular shunt infections. Total supply costs of ventricular shunts significantly decreased by 26% from

Legionella Colonization Prevention in Ice Machines

2345 per procedure in fiscal year 2015 to

Dirty Lines and False Alarms: Blood Culture Contamination in the Emergency Department

1747 per procedure in fiscal year 2016 (P < .001). Total supply cost of dural grafts significantly decreased by 54% from