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We describe a case of catheter-related bacteremia caused by Mycolicibacterium iranicum in the United States. The case highlights the value of using next-generation sequencing to identify infrequent and emerging pathogens and the challenges associated with choosing appropriate treatments because of limited knowledge of drug resistance mechanisms in those emerging pathogens.

IntroductionMacrophage expressed gene 1 (MPEG1) is highly expressed in macrophages and other phagocytes. The gene encodes a bactericidal pore-forming protein, dubbed Perforin-2. Structural-, animal-, and cell-based studies have established that perforin-2 facilitates the destruction of phagocytosed microbes upon its activation within acidic phagosomes. Relative to wild-type controls, Mpeg1 knockout mice suffer significantly higher mortality rates when challenged with gram-negative or -positive pathogens. Only four variants of MPEG1 have been functionally characterized, each in association with pulmonary infections. Here we report a new MPEG1 non-sense variant in a patient with the a newly described association with persistent polymicrobial infections of the skin and soft tissue.Case DescriptionA young adult female patient was evaluated for recurrent abscesses and cellulitis of the breast and demonstrated a heterozygous, rare variant in MPEG1 p.Tyr430*. Multiple courses of broad-spectrum antimicrobials and surgical incision and drainage failed to resolve the infection. Functional studies revealed that the truncation variant resulted in significantly reduced capacity of the patient’s phagocytes to kill intracellular bacteria. Patient-derived macrophages responded to interferon gamma (IFN-γ) by significantly increasing the expression of MPEG1. IFN-γ treatment supported perforin-2 dependent bactericidal activity and wound healing.ConclusionsThis case expands the phenotype of MPEG1 deficiency to include severe skin and soft tissue infection. We showed that haploinsufficiency of perforin-2 reduced the bactericidal capacity of human phagocytes. Interferon-gamma therapy increases expression of perforin-2, which may compensate for such variants. Thus, treatment with IFN-γ could help prevent infections.

OBJECTIVE To identify the source of a pseudo-outbreak of Mycobacterium gordonae DESIGN Outbreak investigation. SETTING University Hospital in Chicago, Ilinois. PATIENTS Hospital patients with M. gordonae-positive clinical cultures. METHODS An increase in isolation of M. gordonae from clinical cultures was noted immediately following the opening of a newly constructed hospital in January 2012. We reviewed medical records of patients with M. gordonae-positive cultures collected between January and December 2012 and cultured potable water specimens in new and old hospitals quantitatively for mycobacteria. RESULTS Of 30 patients with M. gordonae-positive clinical cultures, 25 (83.3%) were housed in the new hospital; of 35 positive specimens (sputum, bronchoalveolar lavage, gastric aspirate), 32 (91.4%) had potential for water contamination. M. gordonae was more common in water collected from the new vs. the old hospital [147 of 157 (93.6%) vs. 91 of 113 (80.5%), P=.001]. Median concentration of M. gordonae was higher in the samples from the new vs. the old hospital (208 vs. 48 colony-forming units (CFU)/mL; P<.001). Prevalence and concentration of M. gordonae were lower in water samples from ice and water dispensers [13 of 28 (46.4%) and 0 CFU/mL] compared with water samples from patient rooms and common areas [225 of 242 (93%) and 146 CFU/mL, P<.001]. CONCLUSIONS M. gordonae was common in potable water. The pseudo-outbreak of M. gordonae was likely due to increased concentrations of M. gordonae in the potable water supply of the new hospital. A silver ion-impregnated 0.5-μm filter may have been responsible for lower concentrations of M. gordonae identified in ice/water dispenser samples. Hospitals should anticipate that construction activities may amplify the presence of waterborne nontuberculous mycobacterial contaminants.

In a comparison of 3 agar plate methods, we found that a novel chromogenic medium, Remel Spectra™ CRE, had the best overall sensitivity (97.8%) when compared to the CHROMagar™ KPC (76.6%) and a direct ertapenem disk method (83.0%) for the detection of blaKPC-positive Enterobacteriaceae from perirectal swabs., (© 2014.)

Objective: To determine anatomic sites of colonization in patients and to assess environmental contamination with Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae., Design, Setting, and Patients: We conducted a cross-sectional microbiologic survey of 33 patients and their environments at 6 long-term acute care hospitals (LTACHs) in metropolitan Chicago. Swab samples of anatomic sites and inanimate surfaces in patients' rooms and common areas were cultured. bla(KPC) was verified by polymerase chain reaction. Patient charts were reviewed for covariates known to be associated with colonization and environmental contamination., Results: Mean age was 66 years. Median length of stay prior to surveillance was 50 days. Thirty (91%) patients were mechanically ventilated, 32 (97%) were bedbound, and 27 (82%) had fecal incontinence. Of the 24 patients with KPC-producing Enterobacteriaceae recovered from 1 or more anatomic sites, 23 (96%) had KPC-producing Enterobacteriaceae detected at 1 or more skin sites. Skin colonization was more common in patients with positive rectal/stool swab cultures or positive clinical cultures ([Formula: see text]). Rectal/stool swab was the single most sensitive specimen for detecting KPC-producing Enterobacteriaceae colonization (sensitivity, 88%; 95% confidence interval [CI], 68%-97%); addition of inguinal skin swab culture resulted in detection of all colonized patients (sensitivity, 100%; 95% CI, 86%-100%). Only 2 (0.5%) of 371 environmental specimens grew KPC-producing Enterobacteriaceae., Conclusions: Culture of more than 1 anatomic site was required to detect all KPC-producing Enterobacteriaceae-colonized patients. Skin colonization was common, but environmental contamination was rare. These results can guide development of multimodal interventions for control of KPC-producing Enterobacteriaceae in LTACHs.

Objective: To determine whether transfer from a long-term care facility (LTCF) is a risk factor for colonization with Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae upon acute care hospital admission., Design: Microbiologic survey and nested case-control study., Setting: Four hospitals in a metropolitan area (Chicago) with an early KPC epidemic., Patients: Hospitalized adults., Methods: Patients transferred from LTCFs were matched 1∶1 to patients admitted from the community by age (± 10 years), admitting clinical service, and admission date (± 2 weeks). Rectal swab specimens were collected within 3 days after admission and tested for KPC-producing Enterobacteriaceae. Demographic and clinical information was extracted from medical records., Results: One hundred eighty patients from LTCFs were matched to 180 community patients. KPC-producing Enterobacteriaceae colonization was detected in 15 (8.3%) of the LTCF patients and 0 (0%) of the community patients ([Formula: see text]). Prevalence of carriage differed by LTCF subtype: 2 of 135 (1.5%) patients from skilled nursing facilities without ventilator care (SNFs) were colonized upon admission, compared to 9 of 33 (27.3%) patients from skilled nursing facilities with ventilator care (VSNFs) and 4 of 12 (33.3%) patients from long-term acute care hospitals (LTACHs; [Formula: see text]). In a multivariable logistic regression model adjusted for a propensity score that predicted LTCF subtype, patients admitted from VSNFs or LTACHs had 7.0-fold greater odds of colonization (ie, odds ratio; 95% confidence interval, 1.3-42; [Formula: see text]) with KPC-producing Enterobacteriaceae than patients from an SNF., Conclusions: Patients admitted to acute care hospitals from high-acuity LTCFs (ie, VSNFs and LTACHs) were more likely to be colonized with KPC-producing Enterobacteriaceae than were patients admitted from the community. Identification of healthcare facilities with a high prevalence of colonized patients presents an opportunity for focused interventions that may aid regional control efforts.

Purpose of Review: Antimicrobial resistance and a paucity of new antimicrobial agents are ongoing challenges. This review focuses on the major epidemiologic trends and novel treatments, when available, for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus, Clostridium difficile, and multidrug-resistant Gram-negative bacilli in the United States during 2010-2011., Recent Findings: MRSA bloodstream infection rates have declined, primarily due to interventions aimed at decreasing vascular catheter infections. The proportion of MRSA due to the community-associated strain USA300 continues to increase. Recent studies of active surveillance and contact isolation for MRSA prevention provide conflicting views of efficacy. Two novel treatments for recurrent C. difficile infection, monoclonal antibodies and fidaxomicin, show promising results. Antimicrobial resistance among Gram-negative bacilli has become widespread; extended-spectrum beta-lactamases are now commonly found among Escherichia coli causing community-acquired infections in the United States. Klebsiella pneumoniae carbapenemases have spread beyond the northeast, and the New Delhi metallo-beta-lactamase has been reported in multiple countries within a few years of its discovery., Summary: Antimicrobial resistance, particularly among Gram-negative bacilli, continues to increase at a rapid rate. Given the frequent transfer of patients between outpatient and acute care settings, as well as between different geographic regions, coordinated infection control interventions are warranted.

We have shown previously that increased extracellular osmolality stimulates expression and promoter activity of the type A natriuretic peptide receptor (NPR-A) gene in rat inner medullary collecting duct (IMCD) cells through a mechanism that involves activation of p38 mitogen-activated protein kinase (MAPK). The serum and glucocorticoid inducible kinase (Sgk) is thought to participate in the regulation of sodium handling in distal tubular segments. We sought to determine whether this kinase might be involved in the osmotic stimulation of NPR-A gene promoter activity. Exposure of cultured IMCD cells to an additional 75 mmol/L NaCl in culture media (final osmolality 475 mosm/kg) resulted in an approximately 4-fold increase in Sgk1 protein levels after 7 hours. The Sgk1 induction was almost completely inhibited by the p38 MAPK inhibitor SB203580, indicating that NaCl activates Sgk1 through the p38 MAPK pathway. Transient transfection of a mouse Sgk1 expression vector along with a -1590 NPR-A luciferase reporter resulted in an approximately 3-fold increment in reporter activity, which was significantly reduced by cotransfection with a kinase-dead Sgk1 mutant. The NaCl-dependent induction was partially blocked (approximately 40% inhibition) by cotransfection of the kinase-dead Sgk1 mutant. Neither Sgk1 nor the kinase-dead mutant had any effect on endothelial nitric oxide synthase (eNOS) promoter activity, and the Sgk1 mutant and 8-bromo-cyclic guanosine monophosphate were, to some degree, additive in reducing osmotically stimulated NPR-A promoter activity. Collectively, these data imply that Sgk1 operates over an eNOS-independent, p38 MAPK-dependent pathway in mediating osmotic induction of the NPR-A gene promoter.

Implications: Two cases of placement of a catheter in the dorsum of a hand into an artery mistaken to be a vein are described. Diagnosis and treatment of such mishaps are discussed.