Cefiderocol Resistance in Acinetobacter baumannii: Roles of ß-Lactamases, Siderophore Receptors, and Penicillin Binding Protein 3.

Cefiderocol is a siderophore cephalosporin active against many multidrug-resistant (MDR) Gram-negative pathogens. We examined the resistance mechanisms in 12 Acinetobacter baumannii strains with cefiderocol MICs ranging from ≤0.03 to >32 µg/ml. Cefiderocol resistance could not be explained by ß-lactamase activity. Cefiderocol resistance was associated with reduced expression of the siderophore receptor gene pirA Mutations involving PBP3 may have contributed to resistance in one strain. Additional studies are needed to assess the role of other siderophore receptors.

In Vitro and In Vivo Activity of Amoxicillin-Clavulanate Combined with Ceftibuten or Cefpodoxime Against Extended-Spectrum ß-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae.

Infections due to extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales are an increasingly common problem. For many of these infections, no oral treatment options are available. The activity of amoxicillin-clavulanate combined with ceftibuten or cefpodoxime was evaluated against a group of Escherichia coli and Klebsiella pneumoniae clinical isolates possessing a variety of CTX-M- and SHV-type ESBLs; some possessed blaTEM1 as well. In time-kill studies, the combination of subinhibitory concentrations of amoxicillin-clavulanate with ceftibuten was bactericidal and synergistic for all strains with an amoxicillin-clavulanate MIC ≤32 µg/mL, regardless of the type of ESBL and the cephalosporin minimal inhibitory concentration (MIC). The combination with cefpodoxime was also bactericidal and synergistic against all but one of these strains. These combinations were further tested against two strains of K. pneumoniae and one E. coli in a sepsis model using Galleria mellonella larvae. The combination of amoxicillin-clavulanate with ceftibuten demonstrated a synergistic survival benefit against all three strains. The combination with cefpodoxime also improved survival against the two K. pneumoniae strains, but not the E. coli strain. These findings support combining amoxicillin-clavulanate with ceftibuten, and possibly cefpodoxime, for the treatment of infections due to ESBL producers and suggest that having an amoxicillin-clavulanate MIC of 32 µg/mL or less may predict activity at clinically achievable concentrations. Clinical studies are warranted to further evaluate this therapeutic approach.

Trends in central-line-associated bloodstream infections and catheter-associated urinary tract infections in a large acute-care hospital system in New York City, 2016-2019.

BACKGROUND: Central-line bloodstream infections (CLABSIs) and catheter-associated urinary tract infections (CAUTIs) negatively impact clinical outcomes and hospital reimbursement. In this report, 4 year trends involving 11 hospitals in New York City were examined. METHODS: Data from the National Healthcare Safety Network (NHSN) were extracted for 11 acute-care hospitals belonging to the NYC Health + Hospital system from 2016 through 2019. Trends in device infections per 1,000 patient days, device utilization ratios, and standardized infection ratios (SIRs) were examined for the 11 hospitals and for the entire system. RESULTS: Over the 4-year period, there were progressive declines in central-line days, infections per 1,000 central-line days, and device utilization ratios for the system. The average annual SIRs for the system also declined: 1.40 in 2016, 1.09 in 2017, 1.04 in 2018, and 0.82 in 2019. Case-mix indices correlated with SIRs for CLABSIs. Level 1 trauma centers had higher SIRs and a disproportionately greater number of CLABSIs in patients located in NHSN-defined surgical intensive care units. Similar trends with CAUTIs were noted, with progressive declines in catheter days, infections per 1,000 patient days, device utilization ratios, and SIRs (1.42 in 2016, 0.93 in 2017, 1.18 in 2018, and 0.78 in 2019) over the 4-year period. CONCLUSIONS: Across an 11-hospital system, continuing efforts to reduce device utilization and infection rates resulted in declining SIRs for CLABSIs and CAUTIs. Hospitals with higher case-mix indices, and particularly level 1 trauma centers, had significantly higher central-line infection rates and SIRs.

Trends in Healthcare Facility-Onset Clostridioides difficile Infection and the Impact of Testing Schemes in an Acute Care Hospital System in New York City, 2016-2019.

BACKGROUND: Healthcare facility-onset Clostridioides difficile infection is associated with adverse clinical outcomes and hospital reimbursement. A four-year review involving eleven hospitals of the NYC Health + Hospital system was undertaken. METHODS: From 2016-2019, infection rates and standardized infection ratios (SIRs) were gathered from National Healthcare Safety Network. The C. difficile testing scheme at each facility was recorded. RESULTS: For the eleven hospitals, declines in rates of C. difficile infection and SIRs were documented. However, this decline was driven by two hospitals that had high rates of infection in 2016; for the remaining nine hospitals, rates of infection and SIRs were at a plateau. Most hospitals used a testing scheme that fell into the nucleic acid amplification test (NAAT) category for SIR risk adjustment. Hospitals that used the algorithm glutamate dehydrogenase (GDH) and toxin A/B immunoassay (EIA) followed by NAAT for discrepant results had significantly lower rates of C. difficile infection but similar SIRs. CONCLUSIONS: For most hospitals in this system, rates of C. difficile remained level. Within the NAAT test categories, SIRs may not correlate with infection rates. Given the controversies regarding testing and calculation of SIRs, alternatives to C. difficile infection should be sought as a hospital quality measurement.

Tocilizumab therapy for COVID-19: A comparison of subcutaneous and intravenous therapies.

BACKGROUND: The release of pro-inflammatory cytokines, resulting in cytokine storm syndrome, contributes to the morbidity and mortality associated with COVID-19 disease. This study aimed to compare the effects of intravenous (IV) and subcutaneous (SC) tocilizumab, an IL-6 receptor antagonist, on respiratory parameters and clinical outcome in patients with COVID 19. METHODS: We performed a retrospective cohort study of hospitalized patients with COVID-19 treated with either IV or SC tocilizumab from March 26, 2020, to May 18, 2020. Respiratory parameters seven days after receiving tocilizumab therapy were compared to baseline measurements. All patients were assessed until discharged from the hospital. RESULTS: Tocilizumab was administered to 125 patients: 65 received IV, and 60 received SC therapy. At day seven, 52% of the IV group patients demonstrated improvement in respiratory parameters, compared to 28% in the SC group (P = 0.01). Mortality rates at days seven and 28 were 15% and 37%, respectively, in the IV group and 17% and 50%, respectively, in the SC group (PNS). The in-hospital mortality rate was 38% for the IV group versus 57% for the SC group (P = 0.04). More than 90% of patients in each group received corticosteroids; however, significantly more patients received convalescent plasma in the IV group. CONCLUSIONS: At the doses used in this study, IV tocilizumab is preferred over SC therapy to treat cytokine storm syndrome due to COVID-19.

Percutaneous Emergence of Gnathostoma spinigerum Following Praziquantel Treatment.

A Bangladeshi patient with prior travel to Saudi Arabia was hospitalized in the United States for a presumptive liver abscess. Praziquantel was administered following a positive Schistosoma antibody test. Ten days later, a subadult worm migrated to the skin surface and was identified morphologically as Gnathostoma spinigerum. This case highlights the challenges of gnathostomiasis diagnosis, raising questions on potential serologic cross-reactivity and the possible role of praziquantel in stimulating outward migration of Gnathostoma larvae/subadults.

Robotic prostatectomy leading to a delayed MRSA infected lymphocele: a case report and review of the literature.

Prostate cancer is the second leading cancer-related cause of death in the USA with the majority presenting as localized disease. In the last decade minimally invasive, robotic-assisted laparascopic, radical prostatectomy has become the most favored treatment choice. A complication that has been observed in 27% of patients is the formation of an asymptomatic lymphocele. It is a very rare complication for these to become infected, and when they do 80% have occurred 2-12 months post-procedure. In this case report the patient presented with fever and leukocytosis of unknown origin and was found to have a methicillin-resistant Staphylococcus aureus (MRSA) infected lymphocele over 2 years after a radical prostatectomy. The infected fluid collection was drained percutaneously and the patient was treated with a 4-week course of intravenous ceftaroline with complete resolution of symptoms.

Hepatotoxicity Associated with Use of the Weight Loss Supplement Garcinia cambogia: A Case Report and Review of the Literature.

The use of herbal and dietary supplements for weight loss is becoming increasingly common as obesity is becoming major health problem in the United States. Despite the popularity of these natural supplements, there are no guidelines for their therapeutic doses and their safety is always a concern. Garcinia cambogia extract with its active ingredient "hydroxycitric acid" is a component of many weight loss regimens. It suppresses fatty acid biosynthesis and decreases appetite. However, its prolonged use in weight maintenance is unknown. Here we describe a case of acute hepatitis after the use of Garcinia cambogia for weight loss.

Gastric siderosis: An under-recognized and rare clinical entity.

The increased deposition of iron in gastric mucosa is known as gastric siderosis. It is believed that the only regulated step of the iron metabolism cycle occurs during absorption in the small intestine. Once this system becomes overwhelmed due to either local or widespread iron levels, then iron can be absorbed very quickly by a passive concentration-dependent mechanism. This excess iron is initially stored in the liver but later can be found in the pancreas, heart and joints. Excess iron is not expected to deposit in the gastric mucosa. This gastric deposition has been found in association with hemochromatosis, oral iron medications, alcohol abuse, blood transfusions, hepatic cirrhosis and spontaneous portacaval shunt with esophageal varices. The precise mechanism of this iron deposition in gastric epithelial and stromal cells is still not well understood; thus, identification of iron in gastric mucosa raises many questions. On histology, the pattern of deposition is variable, and recognition of the pattern is often useful to choose the appropriate workup for the patient and to diagnose and possibly treat the cause of iron overload. In this article, we have described a well-referenced review of this rare clinical entity with different histological patterns, diagnostic tests and the clinical significance of the different patterns of iron deposition.

Metastatic colonic adenocarcinoma in breast: report of two cases and review of the literature.

Metastatic adenocarcinoma to the breast from an extramammary site is extremely rare. In the literature, the most current estimate is that extramammary metastases account for only 0.43% of all breast malignancies and that, of these extramammary sites, colon cancer metastases form a very small subset. Most commonly seen metastasis in breast is from a contralateral breast carcinoma, followed by metastasis from hematopoietic neoplasms, malignant melanoma, sarcoma, lung, prostate, and ovary and gastric neoplasms. Here we present two rare cases, in which colonic adenocarcinomas were found to metastasize to the breast. In both cases, core biopsies were obtained from the suspicious areas identified on mammogram. Histopathology revealed neoplastic proliferation of atypical glandular components within benign breast parenchyma which were morphologically consistent with metastatic adenocarcinoma. By immunohistochemical staining, it was confirmed that the neoplastic components were immunoreactive to colonic markers and nonreactive to breast markers, thus further supporting the morphologic findings. It is extremely important to make this distinction between primary breast cancer and a metastatic process, in order to provide the most effective and appropriate treatment for the patient and to avoid any harmful or unnecessary surgical procedures.

Jorge Lobo's disease: a case of keloidal blastomycosis (lobomycosis) in a nonendemic area.

Lobomycosis or lacaziosis is a chronic subcutaneous fungal infection, caused by the fungus Lacazia loboi, which is phylogenetically related to Coccidioides, Blastomyces, Histoplasma, and Paracoccidioides. The disease was first recognized in 1931 by Jorge Lobo, who found the disease to be a keloidal blastomycosis and named it Jorge Lobo's disease. This case was perplexing initially as this fungal infection is very uncommon in the USA. However, with the ever-increasing frequency of international travel, many more cases of lobomycosis have been diagnosed in areas of nonendemicity, such as the USA, Europe, and South Africa. The clinical histories of such imported fungal infections often illustrate their long latency periods. In lobomycosis, the onset of the disease is usually insidious and often difficult to document. We describe a case of a New York resident who presented with multiple skin nodules over both his arms and forearms, and was subsequently diagnosed with Jorge Lobo's disease. The case, diagnosis, histopathologic findings, complication, and management of this rare clinical disease are discussed.