Multicenter Clinical and Molecular Epidemiological Analysis of Bacteremia Due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE Epicenter of the United States.

Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among Enterobacteriaceae bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (cps), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation. The prevalences of carbapenem resistance among Klebsiella pneumoniae, Enterobacter spp., and Escherichia coli bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were K. pneumoniae and 92% produced K. pneumoniae carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing K. pneumoniae (KPC-Kp). The wzi154 allele, corresponding to cps-2, was present in 93% of KPC-3-Kp, whereas KPC-2-Kp had greater cps diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-Kp had an CAZ-AVI MIC of ≥4/4 µg/ml. There was a median of 47 h from bacteremia onset until active antimicrobial therapy, 38% of patients had septic shock, and 49% died within 30 days. KPC-3-Kp bacteremia (adjusted odds ratio [aOR], 2.58; P = 0.045), cancer (aOR, 3.61, P = 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79; P = 0.03) were independently associated with mortality. Active empirical therapy and combination therapy were not associated with survival. Despite a decade of experience with CRE, patients with CRE bacteremia have protracted delays in appropriate therapies and high mortality rates, highlighting the need for rapid diagnostics and evaluation of new therapeutics.

Multiplex real-time PCR assay for detection and classification of Klebsiella pneumoniae carbapenemase gene (bla KPC) variants.

Carbapenem resistance mediated by plasmid-borne Klebsiella pneumoniae carbapenemases (KPC) is an emerging problem of significant clinical importance in Gram-negative bacteria. Multiple KPC gene variants (bla(KPC)) have been reported, with KPC-2 (bla(KPC-2)) and KPC-3 (bla(KPC-3)) associated with epidemic outbreaks in New York City and various international settings. Here, we describe the development of a multiplex real-time PCR assay using molecular beacons (MB-PCR) for rapid and accurate identification of bla(KPC) variants. The assay consists of six molecular beacons and two oligonucleotide primer pairs, allowing for detection and classification of all currently described bla(KPC) variants (bla(KPC-2) to bla(KPC-11)). The MB-PCR detection limit was 5 to 40 DNA copies per reaction and 4 CFU per reaction using laboratory-prepared samples. The MB-PCR probes were highly specific for each bla(KPC) variant, and cross-reactivity was not observed using DNA isolated from several bacterial species. A total of 457 clinical Gram-negative isolates were successfully characterized by our MB-PCR assay, with bla(KPC-3) and bla(KPC-2) identified as the most common types in the New York/New Jersey metropolitan region. The MB-PCR assay described herein is rapid, sensitive, and specific and should be useful for understanding the ongoing evolution of carbapenem resistance in Gram-negative bacteria. As novel bla(KPC) variants continue to emerge, the MB-PCR assay can be modified in response to epidemiologic developments.

Controlled ovarian stimulation therapy as a potential risk for the development and progression of renal cell carcinomas: A case report and literature review.

Renal Cell Carcinoma (RCC) is the most common type of cancer in the kidney and is mostly asymptomatic. Previous studies have supported the important role of sex hormones in RCC pathophysiology and that targeted hormone receptor therapy, such as estrogen receptor targeting, is a promising treatment strategy. However, to the best of our knowledge, it remains unknown whether hormonal therapy, such as controlled ovarian stimulation for in vitro fertilization, serves a role in the development and progression of RCC. The present report describes a case of RCC developed after a fertility stimulation therapy and provides a summary of the known literature on the role of hormone receptors in the development and progression of RCC. A 35-year-old woman received fertility stimulation treatment with follitropin alfa 900 units, human chorionic gonadotropic hormone 5,000 units, injectable leuprolide 1 mg/0.2 ml and cetrotide 0.25 mg. The patient presented to the hospital with shortness of breath and weight loss. The patient had no known genetic predisposition or family history of malignancies and no exposure to chemicals. The patient never used tobacco, alcohol or recreational drugs. Imaging revealed a 17x19 mm, heterogeneously enhancing, and partially exophytic mass in the right kidney. After partial nephrectomy, the pathological evaluation confirmed the diagnosis of clear cell RCC. To the best of our knowledge, this was the first time that a case of ovarian stimulation therapy was associated with the development of RCC. This case raises concerns about the potential oncogenic effect of controlled ovarian stimulation therapy in RCC promotion, suggesting a need for systematic research to clarify the clinical significance of existing pre-clinical data.

Initial airway management skills of senior residents: simulation training compared with traditional training.

BACKGROUND: Scenario-based training (SBT) with a computerized patient simulator (CPS) is effective in teaching physicians to manage high-risk, low-frequency events that are typical of critical care medicine. This study compares the initial airway management skills of a group of senior internal medicine residents trained using SBT with CPS during their first year of postgraduate training (PGY) with a group of senior internal medicine residents trained using the traditional experiential method. METHODS: This was a prospective, controlled trial that compared two groups of PGY3 internal medicine residents at an urban teaching hospital. One group (n = 32) received training in initial airway management skills using SBT with CPS in their PGY1 (ie, the simulation-trained [ST] group). The second group (n = 30) received traditional residency training (ie, the traditionally trained [TT] group). Each group was then tested during PGY3 in initial airway management skills using a standardized respiratory arrest scenario. RESULTS: The ST group performed significantly better than the TT group in 8 of the 11 steps of the respiratory arrest scenario. Notable differences were found in the ability to attach a bag-valve mask (BVM) to high-flow oxygen (ST group, 69%; TT group, 17%; p < 0.001), correct insertion of oral airway (ST group, 88%; TT group, 20%; p < 0.001), and achieving an effective BVM seal (ST group, 97%; TT group, 20%; p < 0.001). CONCLUSIONS: Traditional training consisting of 2 years of clinical experience was not sufficient to achieve proficiency in initial airway management skills, mostly due to inadequate equipment usage. This suggests that SBT with CPS is more effective in training medical residents than the traditional experiential method.

Achieving housestaff competence in emergency airway management using scenario based simulation training: comparison of attending vs housestaff trainers.

STUDY OBJECTIVES: To evaluate a teaching protocol comparing a critical care attending to a housestaff team in training medical interns in initial airway management skills using a computer-controlled patient simulator (CPS) and scenario-based simulation training (SST). DESIGN: Prospective, randomized, controlled, unblinded trial. SETTING: Internal medicine residency training program in an urban teaching hospital. PARTICIPANTS: Forty-nine starting internal medicine interns in July 2003, all of whom had been certified in advanced cardiac life support in June 2003. INTERVENTIONS: All interns were tested and scored with a CPS while responding to a standardized respiratory arrest scenario. Random allocation to either training by a single experienced teaching attending or by a housestaff team occurred immediately following testing. All interns were retested using the same scenario 6 weeks following the initial training, and their clinical performance of airway management was scored during actual patient events throughout the year. MEASUREMENTS: Initial airway management was divided into specific scorable steps. For each intern, individual step scores and total scores were recorded before and after training. For 10 consecutive months following training, intern airway management scores were recorded for actual patient airway events. RESULTS: All starting medical interns demonstrated poor initial airway management skills. SST was effective in improving these skills, both on retesting with the patient simulator and in actual patient situations. Interns trained by a housestaff team performed as well as interns trained by the attending. CONCLUSIONS: SST is effective in training medical interns, and the results are equivalent whether the training is provided by an experienced teaching attending or by a housestaff training team.

Group G streptococcal myositis in a patient with myeloproliferative neoplasm.

While many cases of streptococcal infection are due to Lancefield groups A and B, there has been a rise in reported cases of infections due to group G streptococcus. We present a case of an individual with a hematologic malignancy who developed myositis secondary to group G streptococcus, with no clearly identifiable source of infection. The patient was managed with antibiotic therapy rather than surgical intervention due to high surgical risk related to severe thrombocytopenia. Targeted antibiotics initiated early in the course of disease may prevent the need for surgical intervention. Early diagnosis and treatment are critical to avoid the high morbidity and mortality of life-threatening infections caused by group G streptococcus.

Challenges in the management of infections due to carbapenem-resistant Enterobacteriaceae.

Carbapenem-resistant Enterobacteriaceae (CRE) infections are increasing and are associated with considerable morbidity and mortality. Members of the Emerging Infections Network treating CRE encountered difficulties in obtaining laboratory results and struggled with limited treatment options. In addition, many treated patients experienced an alarming degree of drug toxicity from CRE therapies.

Molecular epidemiology of Staphylococcus aureus in post-earthquake northern Haiti.

BACKGROUND: Knowledge of nasal carriage is important in predicting staphylococcal infection, and no information exists regarding the endemicity of Staphylococcus aureus in Haiti. METHODS: We performed a cross-sectional analysis of S. aureus nasal screening in an acute care, a subacute rehabilitation, and a community setting, with a brief medical and epidemiological history. PCR-positive S. aureus screening nasal cultures underwent molecular analysis for spa type, SCCmec type, and virulence genes (Panton-Valentine leukocidin (PVL), toxic shock syndrome toxin (TSST), and arginine catabolic mobile element (ACME)), and were evaluated for antibiotic susceptibility using commercial tests. RESULTS: Overall carriage rates of 8.4% methicillin-susceptible S. aureus (MSSA) and 2.8% methicillin-resistant S. aureus (MRSA) were identified, with a high rate of tetracycline resistance. TSST and PVL genes were identified in MSSA. MRSA isolates contained no virulence markers. Unique MSSA phenotypes (i.e., linezolid-resistant, vancomycin-sensitive/daptomycin non-susceptible) were identified, as were two PVL-positive ST152 MSSA colonization isolates, previously geographically limited to Africa. CONCLUSIONS: We found a low S. aureus carriage rate with complete vancomycin susceptibility and high tetracycline resistance, which has important public health implications with regard to treatment. Additionally, the finding of PVL-positive MSSA isolates, including the expansion of a previously described limited 'divergent' clone, ST152, warrants further evaluation.

Finegoldia magna (formerly Peptostreptococcus magnus): an overlooked etiology for toxic shock syndrome?

Finegoldia magna is an anaerobic Gram positive coccus, previously classified as Peptostreoptococcus magnus. It is normal flora of the gastrointestinal and genitourinary tract, and can be isolated from skin and the oral cavity and is often regarded as a contaminant in cultures. As the most frequently isolated anaerobic coccus, it is implicated in a range of mono- and polymicrobial infections, including skin and skin structure, bone and joint (native and prosthetic joints), infective endocarditis (native and prosthetic valves), necrotizing pneumonia, mediastinitis and meningitis. Recently, whole genome sequencing furthered the understanding of the pathogenicity of this organism by elucidating both chromosomally encoded and mobile plasmid mediated virulence factors. Although no cases of toxic shock syndrome have been attributed to F. magna, we present a case of a fatal monomicrobial F. magna bacteremia and hypothesize that superantigen activity, mediated via Protein L binding the variable domain of the κ light chains of IgG, resulted in the syndrome observed in our patient. Additionally, we suspect the overall significance of this pathogen is underestimated and with more sensitive detection methods, this organism will be identified more frequently in clinical cultures and associated with true infection.

Molecular characterization of an early invasive Staphylococcus epidermidis prosthetic joint infection.

Historically regarded as a skin commensal, Staphylococcus epidermidis has been increasingly implicated in invasive foreign body infections such as catheter-related bloodstream infections, indwelling device infections, and prosthetic joint infections. We report a case of an aggressive, difficult-to-eradicate, invasive prosthetic hip infection occurring early after hardware implant and associated with a high-grade bacteremia and assess its salient molecular characteristics. The clinical and molecular characteristics of this isolate mirror the pathogenesis and persistence commonly seen with invasive methicillin-resistant S. aureus and may be attributed to the combination of resistance genes (SCCmec type IV), putative virulence factors (arcA and opp3a), cytolytic peptide production (α-type phenol-soluble modulins), and biofilm adhesion, interaction, and maturation (bhp, aap, and ß-type phenol-soluble modulins).