Colistin is increasingly used as an antibiotic of last resort for the treatment of carbapenem-resistant Gram-negative infections. The plasmid-borne colistin resistance gene mcr-1 was initially identified in animal and clinical samples from China and subsequently reported worldwide, including in the United States. Of particular concern is the spread of mcr-1 into carbapenem-resistant bacteria, thereby creating strains that approach pan-resistance. While several reports of mcr-1 have involved carbapenem-resistant strains, no such isolates have been described in the United States. Here, we report the isolation and identification of an Escherichia coli strain harboring both mcr-1 and carbapenemase gene blaNDM-5 from a urine sample in a patient without recent travel outside the United States. The isolate exhibited resistance to both colistin and carbapenems, but was susceptible to amikacin, aztreonam, gentamicin, nitrofurantoin, tigecycline, and trimethoprim-sulfamethoxazole. The mcr-1- and blaNDM-5-harboring plasmids were completely sequenced and shown to be highly similar to plasmids previously reported from China. The strain in this report was first isolated in August 2014, highlighting an earlier presence of mcr-1 within the United States than previously recognized.
HIV-infected individuals are at increased risk for all forms of extrapulmonary tuberculosis, including tuberculous meningitis. This risk is increased at more advanced levels of immunosuppression. The time interval between onset of symptoms and presentation to medical care may vary widely, and consequently individuals may present with acute or chronic meningitis. The clinical presentation of tuberculous meningitis in HIV-infected individuals is more likely to include an altered level of consciousness, cranial imaging is more likely to show cerebral infarctions, and the yield of culture of cerebrospinal fluid may also be greater. Given that delayed initiation of therapy is a strong predictor of mortality in cases of tuberculous meningitis, clinicians must consider tuberculosis in the differential diagnosis of the HIV-infected individual with acute or chronic lymphocytic meningitis. Additional treatment considerations for HIV-infected individuals include the timing of initiation of antiretroviral therapy, the potential for drug–drug interactions, and the role of adjunctive corticosteroid therapy.
Additional studies are needed to evaluate the role of targeted surveillance measures for NTM disease in high-risk patients, particularly lung transplant recipients, and to characterize the mechanisms of disease acquisition.
SUMMARY
Necrotizing fasciitis is a life-threatening infection requiring urgent surgical and medical therapy. Our objective was to estimate the mortality burden of necrotizing fasciitis in the United States, and to identify time trends in the incidence rate of necrotizing fasciitis-related mortality. We obtained data from the National Center for Health Statistics, which receives information from death certificates from all states, including demographic information and cause of death. The U.S. Multiple Cause of Death Files were searched from 2003 through 2013 for a listing of NF (ICD10 code M72.6) as either the underlying or contributing cause of death. We identified a total of 9,871 necrotizing fasciitis-related deaths in the U.S. between 2003 and 2013 (Figure 1), corresponding to a crude mortality rate of 4.8 deaths per 1,000,000 person-years, without a significant time trend. Compared to white individuals, the incidence rate of necrotizing fasciitis-associated death was greater among black, Hispanic, and American Indian individuals, and lower among Asian individuals. Streptococcal infection was most commonly identified in cases where a pathogen was reported. Diabetes mellitus and obesity were more commonly observed among necrotizing fasciitis-related deaths compared with deaths due to other causes. Racial differences in the incidence of necrotizing fasciitis-related deaths merits further investigation.
The emergence of chronic MABC infections among immunocompromised populations and their inherent and acquired resistance to effective antibiotic therapy have created clinical challenges in advancing patients for transplant surgery and treating those with disease. There is an urgent need for new treatment regimens, and the repurposing of existing antibiotics provides a rapid strategy to advance a laboratory finding to patient care. Our recent discoveries that dual β-lactams, specifically the combination of ceftazidime with ceftaroline or ceftazidime with imipenem, have significant in vitro MIC values and kill curve activities and are effective against infected THP-1 human macrophages provide optimism for a dual β-lactam treatment strategy against MABC infections. The unexpected synergistic activities reported in this study create a new path of discovery to repurpose the large family of β-lactam drugs.
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