Validation of Clinical Risk Models for Clostridioides difficile-Attributable Outcomes.

Clostridioides difficile is the leading health care-associated pathogen, leading to substantial morbidity and mortality; however, there is no widely accepted model to predict C. difficile infection severity. Most currently available models perform poorly or were calibrated to predict outcomes that are not clinically relevant. We sought to validate six of the leading risk models (Age Treatment Leukocyte Albumin Serum Creatinine (ATLAS), C. difficile Disease (CDD), Zar, Hensgens, Shivashankar, and C. difficile Severity Score (CDSS)), guideline severity criteria, and PCR cycle threshold for predicting C. difficile-attributable severe outcomes (inpatient mortality, colectomy/ileostomy, or intensive care due to sepsis). Models were calculated using electronic data available within ±48 h of diagnosis (unavailable laboratory measurements assigned zero points), calibrated using a large retrospective cohort of 3,327 inpatient infections spanning 10 years, and compared using receiver operating characteristic (ROC) and precision-recall curves. ATLAS achieved the highest area under the ROC curve (AuROC) of 0.781, significantly better than the next best performing model (Zar 0.745; 95% confidence interval of AuROC difference 0.0094-0.6222; P = 0.008), and highest area under the precision-recall curve of 0.232. Current IDSA/SHEA severity criteria demonstrated moderate performance (AuROC 0.738) and PCR cycle threshold performed the worst (0.531). The overall predictive value for all models was low, with a maximum positive predictive value of 37.9% (ATLAS cutoff ≥9). No clinical model performed well on external validation, but ATLAS did outperform other models for predicting clinically relevant C. difficile-attributable outcomes at diagnosis. Novel markers should be pursued to augment or replace underperforming clinical-only models.

Human Rabies - Virginia, 2017.

On May 9, 2017, the Virginia Department of Health was notified regarding a patient with suspected rabies. The patient had sustained a dog bite 6 weeks before symptom onset while traveling in India. On May 11, CDC confirmed that the patient was infected with a rabies virus that circulates in dogs in India. Despite aggressive treatment, the patient died, becoming the ninth person exposed to rabies abroad who has died from rabies in the United States since 2008. A total of 250 health care workers were assessed for exposure to the patient, 72 (29%) of whom were advised to initiate postexposure prophylaxis (PEP). The total pharmaceutical cost for PEP (rabies immunoglobulin and rabies vaccine) was approximately $235,000. International travelers should consider a pretravel consultation with travel health specialists; rabies preexposure prophylaxis is warranted for travelers who will be in rabies endemic countries for long durations, in remote areas, or who plan activities that might put them at risk for a rabies exposures.

Intensive Care Unit Wastewater Interventions to Prevent Transmission of Multispecies Klebsiella pneumoniae Carbapenemase-Producing Organisms.

Background: The increasing prevalence of nosocomial carbapenemase-producing Enterobacteriaceae is a concern. However, the role of the environment in multispecies outbreaks remains poorly understood. There is increasing recognition that hospital wastewater plumbing may play a role. Methods: Covers were installed on all hoppers (a "toilet-like" waste disposal system) in adult intensive care units (ICUs) of a university hospital; additionally in the surgical ICU, sink trap heating and vibration devices were also installed. Patient acquisitions of Klebsiella pneumoniae carbapenemase-producing organisms (KPCOs) for patients who were admitted to an intervention unit were compared for 18-month preintervention and intervention periods. Results: Sixty hopper covers and 23 sink trap devices were installed. Fifty-six new multispecies KPCO acquisitions occurred preintervention compared to 30 during the intervention. Decreases for all KPCO acquisitions (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.31-0.81; P = .003) and KPCO-positive clinical cultures (OR, 0.29; 95% CI, 0.17-0.48; P < .001) per admission in patients exposed to an intervention unit were observed. The incidence rate ratio was 0.51-fold (95% CI, 0.43-0.61) lower for all KPCO acquisitions during the intervention. The effect of the sink trap devices alone could not be determined, although the proportion of sink drain cultures positive for KPCO decreased (12/15 [80%] sites sampled preintervention vs 40/840 [5%] sampled during the intervention; P = .001). Conclusions: An intervention targeting wastewater plumbing fixtures, by installation of hopper covers, demonstrated a decrease in patient KPCO acquisitions. Considering wastewater reservoirs in nosocomial transmission of multispecies carbapenemase-producing Enterobacteriaceae may be critical.

Late post-kidney transplant Strongyloides hyperinfection syndrome.

Disseminated strongyloidiasis is a potentially life-threatening infection in organ transplant recipients that typically occurs within the first 6 months of transplantation. We discuss a patient from the Appalachia region of Virginia who appeared to acquire Strongyloides stercoralis domestically years after kidney transplantation and then develop disseminated strongyloidiasis.

Chromosomal Integration of the Klebsiella pneumoniae Carbapenemase Gene, blaKPC, in Klebsiella Species Is Elusive but Not Rare.

Carbapenemase genes in Enterobacteriaceae are mostly described as being plasmid associated. However, the genetic context of carbapenemase genes is not always confirmed in epidemiological surveys, and the frequency of their chromosomal integration therefore is unknown. A previously sequenced collection of blaKPC-positive Enterobacteriaceae from a single U.S. institution (2007 to 2012; n = 281 isolates from 182 patients) was analyzed to identify chromosomal insertions of Tn4401, the transposon most frequently harboring blaKPC Using a combination of short- and long-read sequencing, we confirmed five independent chromosomal integration events from 6/182 (3%) patients, corresponding to 15/281 (5%) isolates. Three patients had isolates identified by perirectal screening, and three had infections which were all successfully treated. When a single copy of blaKPC was in the chromosome, one or both of the phenotypic carbapenemase tests were negative. All chromosomally integrated blaKPC genes were from Klebsiella spp., predominantly K. pneumoniae clonal group 258 (CG258), even though these represented only a small proportion of the isolates. Integration occurred via IS15-ΔI-mediated transposition of a larger, composite region encompassing Tn4401 at one locus of chromosomal integration, seen in the same strain (K. pneumoniae ST340) in two patients. In summary, we identified five independent chromosomal integrations of blaKPC in a large outbreak, demonstrating that this is not a rare event. blaKPC was more frequently integrated into the chromosome of epidemic CG258 K. pneumoniae lineages (ST11, ST258, and ST340) and was more difficult to detect by routine phenotypic methods in this context. The presence of chromosomally integrated blaKPC within successful, globally disseminated K. pneumoniae strains therefore is likely underestimated.

Enhanced Klebsiella pneumoniae Carbapenemase Expression from a Novel Tn4401 Deletion.

The Klebsiella pneumoniae carbapenemase gene (blaKPC) is typically located within mobile transposon Tn4401 Enhanced KPC expression has been associated with deletions in the putative promoter region upstream of blaKPC Illumina sequences from blaKPC-positive clinical isolates from a single institution were mapped to a Tn4401b reference sequence, which carries no deletions. The novel isoform Tn4401h (188-bp deletion [between istB and blaKPC]) was present in 14% (39/281) of clinical isolates. MICs showed that Escherichia coli strains containing plasmids with Tn4401a and Tn4401h were more resistant to meropenem (≥16 and ≥16, respectively), ertapenem (≥8 and 4, respectively), and cefepime (≥64 and 4, respectively) than E. coli strains with Tn4401b (0.5, ≤0.5, and ≤1, respectively). Quantitative real-time PCR (qRT-PCR) demonstrated that Tn4401a had a 16-fold increase and Tn4401h a 4-fold increase in blaKPC mRNA levels compared to the reference Tn4401b. A lacZ reporter plasmid was used to test the activity of the promoter regions from the different variants, and the results showed that the Tn4401a and Tn4401h promoter sequences generated higher ß-galactosidase activity than the corresponding Tn4401b sequence. Further dissection of the promoter region demonstrated that putative promoter P1 was not functional. The activity of the isolated P2 promoter was greatly enhanced by inclusion of the P1-P2 intervening sequence. These studies indicated that gene expression could be an important consideration in understanding resistance phenotypes predicted by genetic signatures in the context of sequencing-based rapid diagnostics.

Unique characteristics of cryptococcosis identified after death in patients with liver cirrhosis: comparison with concurrent cohort diagnosed antemortem.

Characteristics of cirrhosis-associated cryptococcosis first diagnosed after death are not fully known. In a multicenter study, data generated as standard of care was systematically collected in 113 consecutive patients with cirrhosis and cryptococcosis followed for 80 patient-years. The diagnosis of cryptococcosis was first established after death in 15.9% (18/113) of the patients. Compared to cases diagnosed while alive, these patients had higher MELD score (33 vs. 22, P = .029) and higher rate of cryptococcemia (75.0% vs. 41.9%, P = .027). Cases diagnosed after death, in comparison to those diagnosed during life were more likely to present with shock (OR 3.42, 95% CI 1.18-9.90, P = .023), require mechanical ventilation at admission (OR 8.5, 95% CI 2.74-26.38, P = .001), less likely to undergo testing for serum cryptococcal antigen (OR 0.07, 95% CI 0.02-0.21, P < .001) and have positive antigen when the test was performed (OR 0.07, 95% CI 0.01-0.60, P = .016). In a subset of cirrhotic patients with advanced liver disease cryptococcosis was first recognized after death. These patients had the characteristics of presenting with fulminant fungemia, were less likely to have positive serum cryptococcal antigen and posed a diagnostic challenge for care providers.

Influence of Minimum Inhibitory Concentration in Clinical Outcomes of Enterococcus faecium Bacteremia Treated With Daptomycin: Is it Time to Change the Breakpoint?

BACKGROUND: Daptomycin has become a front-line antibiotic for multidrug-resistant Enterococcus faecium bloodstream infections (BSIs). We previously showed that E. faecium strains with daptomycin minimum inhibitory concentrations (MICs) in the higher end of susceptibility frequently harbor mutations associated with daptomycin resistance. We postulate that patients with E. faecium BSIs exhibiting daptomycin MICs of 3-4 µg/mL treated with daptomycin are more likely to have worse clinical outcomes than those exhibiting daptomycin MICs ≤2 µg/mL. METHODS: We conducted a multicenter retrospective cohort study that included adult patients with E. faecium BSI for whom initial isolates, follow-up blood culture data, and daptomycin administration data were available. A central laboratory performed standardized daptomycin MIC testing for all isolates. The primary outcome was microbiologic failure, defined as clearance of bacteremia ≥4 days after the index blood culture. The secondary outcome was all-cause in-hospital mortality. RESULTS: A total of 62 patients were included. Thirty-one patients were infected with isolates that exhibited daptomycin MICs of 3-4 µg/mL. Overall, 34 patients had microbiologic failure and 25 died during hospitalization. In a multivariate logistic regression model, daptomycin MICs of 3-4 µg/mL (odds ratio [OR], 4.7 [1.37-16.12]; P = .014) and immunosuppression (OR, 5.32 [1.20-23.54]; P = .028) were significantly associated with microbiologic failure. Initial daptomycin dose of ≥8 mg/kg was not significantly associated with evaluated outcomes. CONCLUSIONS: Daptomycin MICs of 3-4 µg/mL in the initial E. faecium blood isolate predicted microbiological failure of daptomycin therapy, suggesting that modification in the daptomycin breakpoint for enterococci should be considered.

Nested Russian Doll-Like Genetic Mobility Drives Rapid Dissemination of the Carbapenem Resistance Gene blaKPC.

The recent widespread emergence of carbapenem resistance in Enterobacteriaceae is a major public health concern, as carbapenems are a therapy of last resort against this family of common bacterial pathogens. Resistance genes can mobilize via various mechanisms, including conjugation and transposition; however, the importance of this mobility in short-term evolution, such as within nosocomial outbreaks, is unknown. Using a combination of short- and long-read whole-genome sequencing of 281 blaKPC-positive Enterobacteriaceae isolates from a single hospital over 5 years, we demonstrate rapid dissemination of this carbapenem resistance gene to multiple species, strains, and plasmids. Mobility of blaKPC occurs at multiple nested genetic levels, with transmission of blaKPC strains between individuals, frequent transfer of blaKPC plasmids between strains/species, and frequent transposition of blaKPC transposon Tn4401 between plasmids. We also identify a common insertion site for Tn4401 within various Tn2-like elements, suggesting that homologous recombination between Tn2-like elements has enhanced the spread of Tn4401 between different plasmid vectors. Furthermore, while short-read sequencing has known limitations for plasmid assembly, various studies have attempted to overcome this by the use of reference-based methods. We also demonstrate that, as a consequence of the genetic mobility observed in this study, plasmid structures can be extremely dynamic, and therefore these reference-based methods, as well as traditional partial typing methods, can produce very misleading conclusions. Overall, our findings demonstrate that nonclonal resistance gene dissemination can be extremely rapid, presenting significant challenges for public health surveillance and achieving effective control of antibiotic resistance.

Predictors of immune reconstitution syndrome in organ transplant recipients with cryptococcosis: implications for the management of immunosuppression.

BACKGROUND: Risk factors including how changes in immunosuppression influence the occurrence of immune reconstitution syndrome (IRS) in solid organ transplant (SOT) recipients with cryptococcosis have not been fully defined. METHODS: SOT recipients with cryptococcosis were identified and followed for 12 months. IRS was defined based on previously proposed criteria. RESULTS: Of 89 SOT recipients, 13 (14%) developed IRS. Central nervous system (CNS) disease (adjusted odds ratio [AOR], 6.23; P = .03) and discontinuation of calcineurin inhibitor (AOR, 5.11; P = .02) were independently associated with IRS. Only 2.6% (1/13) of the patients without these risk factors developed IRS compared with 18.8% (6/32) with 1 risk factor, and 50% (6/12) with both risk factors (χ(2) for trend, P = .0001). Among patients with CNS disease, those with neuroimaging abnormalities (P = .03) were more likely to develop IRS, irrespective of serum or CSF cryptococcal antigen titers and fungemia. Graft rejection after cryptococcosis was observed in 15.4% (2/13) of the patients with IRS compared with 2.6% (2/76) of those without IRS (P = .07). CONCLUSIONS: We determined variables that pose a risk for IRS and have shown that discontinuation of calcineurin inhibitors was independently associated with 5-fold increased risk of IRS in transplant recipients with cryptococcosis.

Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae at a single institution: insights into endemicity from whole-genome sequencing.

The global emergence of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) multilocus sequence type ST258 is widely recognized. Less is known about the molecular and epidemiological details of non-ST258 K. pneumoniae in the setting of an outbreak mediated by an endemic plasmid. We describe the interplay of blaKPC plasmids and K. pneumoniae strains and their relationship to the location of acquisition in a U.S. health care institution. Whole-genome sequencing (WGS) analysis was applied to KPC-Kp clinical isolates collected from a single institution over 5 years following the introduction of blaKPC in August 2007, as well as two plasmid transformants. KPC-Kp from 37 patients yielded 16 distinct sequence types (STs). Two novel conjugative blaKPC plasmids (pKPC_UVA01 and pKPC_UVA02), carried by the hospital index case, accounted for the presence of blaKPC in 21/37 (57%) subsequent cases. Thirteen (35%) isolates represented an emergent lineage, ST941, which contained pKPC_UVA01 in 5/13 (38%) and pKPC_UVA02 in 6/13 (46%) cases. Seven (19%) isolates were the epidemic KPC-Kp strain, ST258, mostly imported from elsewhere and not carrying pKPC_UVA01 or pKPC_UVA02. Using WGS-based analysis of clinical isolates and plasmid transformants, we demonstrate the unexpected dispersal of blaKPC to many non-ST258 lineages in a hospital through spread of at least two novel blaKPC plasmids. In contrast, ST258 KPC-Kp was imported into the institution on numerous occasions, with other blaKPC plasmid vectors and without sustained transmission. Instead, a newly recognized KPC-Kp strain, ST941, became associated with both novel blaKPC plasmids and spread locally, making it a future candidate for clinical persistence and dissemination.

Enhanced pathogenicity of biofilm-negative Staphylococcus epidermidis isolated from platelet preparations.

BACKGROUND: The platelet (PLT) storage environment triggers the formation of surface-attached aggregates known as biofilms by the common PLT contaminant Staphylococcus epidermidis. The biofilm matrix is largely composed of polysaccharide intercellular adhesin (PIA) mediated by the icaADBC operon. However, PIA-negative S. epidermidis has been reported to form biofilms in PLT concentrates (PCs). Since biofilm formation is associated with increased virulence, this study was aimed at determining if PIA-negative S. epidermidis grown in PCs presents enhanced virulence using the nematode Caenorhabditis elegans as a host model for bacterial pathogenesis. STUDY DESIGN AND METHODS: Biofilm-positive S. epidermidis ATCC 35984 and 9142, which carry the icaADBC operon, and biofilm-negative S. epidermidis ATCC 12228 and 9142 ΔicaA were grown in regular media and in PCs and biofilm formation was quantified using a crystal violet assay. The virulence of these strains after passage through PCs was tested using nematode killing assays. Nematode survival was calculated using the Kaplan-Meier method and statistical differences were determined by log-rank analysis. RESULTS: All S. epidermidis strains were able to form biofilms in PCs. Although persistence of a biofilm-positive phenotype in the biofilm-negative strains grown in PCs was not observed after passage in regular medium, the virulence of all strains was significantly increased as demonstrated by shortened life spans of the nematodes in C. elegans killing assays. CONCLUSION: Our findings highlight the potential of an increased risk of nosocomial infections caused by S. epidermidis in transfusion recipients since PC storage conditions promote biofilm formation, and possibly pathogenicity, of strains traditionally known to be attenuated for virulence.

Biofilm-forming skin microflora bacteria are resistant to the bactericidal action of disinfectants used during blood donation.

BACKGROUND: A one-step skin disinfection method containing 2% chlorhexidine-gluconate (CHG) and 70% isopropyl alcohol (IPA) is currently used by blood suppliers worldwide. Reports of bacterially contaminated platelet concentrates (PCs) indicate that skin disinfection is not fully effective. Approximately 20% of skin microflora exist as surface-attached aggregates (biofilms), known for displaying increased resistance to disinfectants. This study was aimed at determining whether skin microflora biofilm-positive Staphylococcus epidermidis and Staphylococcus capitis are resistant to CHG and/or IPA. STUDY DESIGN AND METHODS: Free-floating cells and mono or dual (1 : 1 ratio) biofilms of S. epidermidis and S. capitis were exposed to CHG, IPA, or CHG/IPA for 30 seconds, simulating skin disinfection practices. Residual viable cells were quantified by colony counting. Morphology of disinfectant-treated S. epidermidis biofilms was examined by scanning electron microscopy. Treated S. epidermidis and S. capitis biofilms were inoculated into PCs and bacterial concentrations were determined on Days 0 and 5 of storage. RESULTS: Treatment of staphylococcal biofilm cells with all disinfectants caused cell damage and significant reduction in viability, with CHG/IPA being the most effective. However, biofilms were significantly more resistant to treatment than free-floating cells. Disinfectant-treated S. epidermidis proliferated better in PCs than S. capitis, especially when grown as monospecies biofilms. CONCLUSION: Although CHG/IPA is effective in reducing the viability of S. epidermidis and S. capitis biofilms, these organisms are not completely eliminated. Furthermore, disinfectant-treated staphylococcal biofilms multiply well in PCs. These results demonstrate that the biofilm-forming capability of the skin microflora reduces the bactericidal efficiency of blood donor skin disinfectants.

Brain angiogenesis inhibitor 1 (BAI1) is a pattern recognition receptor that mediates macrophage binding and engulfment of Gram-negative bacteria.

Bacterial recognition by host cells is essential for initiation of infection and the host response. Bacteria interact with host cells via multiple pattern recognition receptors that recognize microbial products or pathogen-associated molecular patterns. In response to this interaction, host cell signaling cascades are activated that lead to inflammatory responses and/or phagocytic clearance of attached bacteria. Brain angiogenesis inhibitor 1 (BAI1) is a receptor that recognizes apoptotic cells through its conserved type I thrombospondin repeats and triggers their engulfment through an ELMO1/Dock/Rac1 signaling module. Because thrombospondin repeats in other proteins have been shown to bind bacterial surface components, we hypothesized that BAI1 may also mediate the recognition and clearance of pathogenic bacteria. We found that preincubation of bacteria with recombinant soluble BAI1 ectodomain or knockdown of endogenous BAI1 in primary macrophages significantly reduced binding and internalization of the Gram-negative pathogen Salmonella typhimurium. Conversely, overexpression of BAI1 enhanced attachment and engulfment of Salmonella in macrophages and in heterologous nonphagocytic cells. Bacterial uptake is triggered by the BAI1-mediated activation of Rac through an ELMO/Dock-dependent mechanism, and inhibition of the BAI1/ELMO1 interaction prevents both Rac activation and bacterial uptake. Moreover, inhibition of ELMO1 or Rac function significantly impairs the proinflammatory response to infection. Finally, we show that BAI1 interacts with a variety of Gram-negative, but not Gram-positive, bacteria through recognition of their surface lipopolysaccharide. Together these findings identify BAI1 as a pattern recognition receptor that mediates nonopsonic phagocytosis of Gram-negative bacteria by macrophages and directly affects the host response to infection.

Modeling relaxed policies for discontinuation of methicillin-resistant Staphylococcus aureus contact precautions.

OBJECTIVE: To evaluate the economic costs of reducing the University of Virginia Hospital's present "3-negative" policy, which continues methicillin-resistant Staphylococcus aureus (MRSA) contact precautions until patients receive 3 consecutive negative test results, to either 2 or 1 negative. DESIGN: Cost-effective analysis. SETTINGS: The University of Virginia Hospital. PATIENTS: The study included data from 41,216 patients from 2015 to 2019. METHODS: We developed a model for MRSA transmission in the University of Virginia Hospital, accounting for both environmental contamination and interactions between patients and providers, which were derived from electronic health record (EHR) data. The model was fit to MRSA incidence over the study period under the current 3-negative clearance policy. A counterfactual simulation was used to estimate outcomes and costs for 2- and 1-negative policies compared with the current 3-negative policy. RESULTS: Our findings suggest that 2-negative and 1-negative policies would have led to 6 (95% CI, -30 to 44; P < .001) and 17 (95% CI, -23 to 59; -10.1% to 25.8%; P < .001) more MRSA cases, respectively, at the hospital over the study period. Overall, the 1-negative policy has statistically significantly lower costs ($628,452; 95% CI, $513,592-$752,148) annually (P < .001) in US dollars, inflation-adjusted for 2023) than the 2-negative policy ($687,946; 95% CI, $562,522-$812,662) and 3-negative ($702,823; 95% CI, $577,277-$846,605). CONCLUSIONS: A single negative MRSA nares PCR test may provide sufficient evidence to discontinue MRSA contact precautions, and it may be the most cost-effective option.

Transmission of hepatitis B virus from an orthopedic surgeon with a high viral load.

BACKGROUND: During the evaluation of a needle-stick injury, an orthopedic surgeon was found to be unknowingly infected with hepatitis B virus (HBV) (viral load >17.9 million IU/mL). He had previously completed two 3-dose series of hepatitis B vaccine without achieving a protective level of surface antibody. We investigated whether any surgical patients had acquired HBV infection while under his care. METHODS: A retrospective cohort study of all patients who underwent surgery by the surgeon was conducted. Patients were notified of their potential exposure and need for testing, and samples with positive HBV loads underwent DNA sequencing. Characteristics of the surgical procedures for the cohort were evaluated. RESULTS: A total of 232 (70.7%) of potentially exposed patients consented to testing; 2 were found to have acute infection and 6 had possible transmission (evidence of past exposure without risk factors). Genome sequence analysis of HBV DNA from the infected surgeon and patients with acute infection revealed genetically related virus (>99.9% nucleotide identity). Only age was found to be statistically different between those with confirmed or possible HBV transmission and those who remained susceptible to HBV. CONCLUSIONS: We documented HBV transmission during orthopedic surgery to 2 patients from a surgeon with HBV. This investigation highlights the importance of evaluating individuals who do not respond to 2 series of HBV vaccination, the increased risk of HBV transmission from providers with high viral loads, and the need to evaluate the clinical practice of providers with HBV and implement appropriate procedure-based practice restrictions.

Modified Hodge test versus indirect carbapenemase test: prospective evaluation of a phenotypic assay for detection of Klebsiella pneumoniae carbapenemase (KPC) in Enterobacteriaceae.

The currently recommended phenotypic test for the detection of carbapenemase-producing members of the family Enterobacteriaceae is the modified Hodge test (MHT). However, the MHT lacks specificity. Here we demonstrate an alternative phenotypic test, the indirect carbapenemase test, for the detection of blaKPC-producing isolates that has specificity superior to that of the MHT for non-Klebsiella Enterobacteriaceae.

First clinical cases of OXA-48-producing carbapenem-resistant Klebsiella pneumoniae in the United States: the "menace" arrives in the new world.

OXA-48 has emerged as a major carbapenemase associated with the Enterobacteriaceae in Europe, North Africa, and Asia. We report the first two clinical cases of OXA-48-type carbapenemase-producing Enterobacteriaceae in the United States from patients recently hospitalized in Saudi Arabia and India. Each is more carbapenem resistant than nearly all previously reported OXA-48-type-producing Enterobacteriaceae.