Two cases of fungal keratitis caused by Metarhizium anisopliae

We present two cases of keratitis due to Metarhizium anisopliae in geographically separated areas of the United States. The isolates were microscopically similar but morphologically different and were identified by ribosomal DNA sequencing. Both isolates had low minimum inhibitory concentration (MIC) values to caspofungin and micafungin, but high MIC values to amphotericin B. The morphologic and antifungal susceptibility differences between the two isolates indicate possible polyphylogeny of the group. Keywords: Metarhizium, Fungal keratitis, Keratomycosis, Antifungal susceptibilit

Carbapenemase-producing organisms: a global scourge

The dramatic increase in the prevalence and clinical impact of infections caused by bacteria producing carbapenemases is a global health concern. Carbapenemase production is especially problematic when encountered in members of the family Enterobacteriaceae. Due to their ability to readily spread and colonize patients in healthcare environments, preventing the transmission of these organisms is a major public health initiative and coordinated international effort are needed. Central to the treatment and control of carbapenemase-producing organisms (CPOs) are phenotypic (growth-/biochemical-dependent) and nucleic acid–based carbapenemase detection tests that identify carbapenemase activity directly or their associated molecular determinants. Importantly, bacterial isolates harboring carbapenemases are often resistant to multiple antibiotic classes, resulting in limited therapy options. Emerging agents, novel antibiotic combinations and treatment regimens offer promise for management of these infections. This review highlights our current understanding of CPOs with emphasis on their epidemiology, detection, treatment, and control

Are we there yet? Laboratory preparedness for emerging infectious diseases

The West African Ebola virus epidemic of 2013–2016 was the most widespread epidemic of this disease in history; it is estimated that this occurrence contributed to more than 11000 deaths. During the epidemic, healthcare workers (HCW)8 (including laboratorians) were mobilized to care for individuals with suspected or confirmed Ebola virus disease (EVD). However, at the height of the epidemic, guidance on appropriate safety measures for laboratory workers manipulating specimens from EVD patients was sparse. This highlighted the need for data and guidelines for laboratories testing specimens not only for patients with EVD, but for any emerging infectious disease. During the Ebola epidemic, questions were raised about the roles and responsibilities of laboratories in responding to highly infectious diseases, and the burden of ongoing readiness for rare events. As the outbreak decelerates, laboratorians must regroup, gather data, and prepare for future outbreaks. We have asked 4 experts in this field to share their thoughts on contemporary challenges in laboratory preparedness for emerging infectious disease

Characteristics and Antibiotic Use Associated With Short-Term Risk of Clostridium difficile Infection Among Hospitalized Patients

Objectives—Polymerase chain reaction (PCR) has been shown to have an excellent sensitivity and specificity for the detection of Clostridium difficile infection (CDI). Little is known about risk factors for CDI within 14 days of an initial negative test. We sought to determine the characteristics among hospitalized patients associated with risk of short-term acquisition of CDI. Methods—A case-control study was conducted. Cases were patients who converted from PCR negative to positive within 14 days. Each case was matched with three controls. Conditional logistic regression was used to estimate the association between patient characteristics and CDI. Results—Of the 30 patients in our study who had a positive PCR within 14 days of a first negative PCR (cases), 15 (50%) occurred within 7 days of the initial test. Cases had a higher proportion of intravenous vancomycin use in the previous 8 weeks (odds ratio [OR], 3.38; 95% confidence interval [CI], 1.34-8.49) and were less likely to have recent antiviral agent use (OR, 0.30; 95% CI, 0.11-0.83) compared with controls. Conclusions—In hospitalized patients, treatment with intravenous vancomycin within the prior 8 weeks of a first negative PCR test for C difficile is a risk factor for short-term risk for hospital-acquired CDI. Repeat testing guidelines for C difficile PCR should take into consideration patients who may be at high risk for short-term acquisition of CDI

Intestine-specific deletion of microsomal triglyceride transfer protein increases mortality in aged mice

BACKGROUND:Mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO) exhibit a complete block in chylomicron assembly together with lipid malabsorption. Young (8-10 week) Mttp-IKO mice have improved survival when subjected to a murine model of Pseudomonas aeruginosa-induced sepsis. However, 80% of deaths in sepsis occur in patients over age 65. The purpose of this study was to determine whether age impacts outcome in Mttp-IKO mice subjected to sepsis. METHODS:Aged (20-24 months) Mttp-IKO mice and WT mice underwent intratracheal injection with P. aeruginosa. Mice were either sacrificed 24 hours post-operatively for mechanistic studies or followed seven days for survival. RESULTS:In contrast to young septic Mttp-IKO mice, aged septic Mttp-IKO mice had a significantly higher mortality than aged septic WT mice (80% vs. 39%, p = 0.005). Aged septic Mttp-IKO mice exhibited increased gut epithelial apoptosis, increased jejunal Bax/Bcl-2 and Bax/Bcl-XL ratios yet simultaneously demonstrated increased crypt proliferation and villus length. Aged septic Mttp-IKO mice also manifested increased pulmonary myeloperoxidase levels, suggesting increased neutrophil infiltration, as well as decreased systemic TNFα compared to aged septic WT mice. CONCLUSIONS:Blocking intestinal chylomicron secretion alters mortality following sepsis in an age-dependent manner. Increases in gut apoptosis and pulmonary neutrophil infiltration, and decreased systemic TNFα represent potential mechanisms for why intestine-specific Mttp deletion is beneficial in young septic mice but harmful in aged mice as each of these parameters are altered differently in young and aged septic WT and Mttp-IKO mice

Microfluidic Amperometric Sensor for Analysis of Nitric Oxide in Whole Blood

Standard photolithographic techniques and a nitric oxide (NO) selective xerogel polymer were utilized to fabricate an amperometric NO microfluidic sensor with low background noise and the ability to analyze NO levels in small sample volumes (~250 μL). The sensor exhibited excellent analytical performance in phosphate buffered saline, including a NO sensitivity of 1.4 pA nM−1, a limit of detection (LOD) of 840 pM, and selectivity over nitrite, ascorbic acid, acetaminophen, uric acid, hydrogen sulfide, ammonium, ammonia, and both protonated and deprotonated peroxynitrite (selectivity coefficients of −5.3, −4.2, −4.0, −5.0, −6.0, −5.8, −3.8, −1.5, and −4.0 respectively). To demonstrate the utility of the microfluidic NO sensor for biomedical analysis, the device was used to monitor changes in blood NO levels during the onset of sepsis in a murine pneumonia model

Human Papillomavirus and Cervical Cancer

Of the many types of human papillomavirus (HPV), more than 30 infect the genital tract. The association between certain oncogenic (high-risk) strains of HPV and cervical cancer is well established. Although HPV is essential to the transformation of cervical epithelial cells, it is not sufficient, and a variety of cofactors and molecular events influence whether cervical cancer will develop. Early detection and treatment of precancerous lesions can prevent progression to cervical cancer. Identification of precancerous lesions has been primarily by cytologic screening of cervical cells. Cellular abnormalities, however, may be missed or may not be sufficiently distinct, and a portion of patients with borderline or mildly dyskaryotic cytomorphology will have higher-grade disease identified by subsequent colposcopy and biopsy. Sensitive and specific molecular techniques that detect HPV DNA and distinguish high-risk HPV types from low-risk HPV types have been introduced as an adjunct to cytology. Earlier detection of high-risk HPV types may improve triage, treatment, and follow-up in infected patients. Currently, the clearest role for HPV DNA testing is to improve diagnostic accuracy and limit unnecessary colposcopy in patients with borderline or mildly abnormal cytologic test results