Neurovascular Complications of Iatrogenic Fusarium solani Meningitis.

A multinational outbreak of nosocomial fusarium meningitis occurred among immunocompetent patients who had undergone surgery with epidural anesthesia in Mexico. The pathogen involved had a high predilection for the brain stem and vertebrobasilar arterial system and was associated with high mortality from vessel injury. Effective treatment options remain limited; in vitro susceptibility testing of the organism suggested that it is resistant to all currently approved antifungal medications in the United States. To highlight the severe complications associated with fusarium infection acquired in this manner, we report data, clinical courses, and outcomes from 13 patients in the outbreak who presented with symptoms after a median delay of 39 days.

Evolving landscape of carbapenem-resistant Pseudomonas aeruginosa at a single centre in the USA.

Objectives: The increased identification of carbapenem-resistant Pseudomonas aeruginosa (CR-PA) is an ongoing concern. However, information on the evolving antimicrobial resistance profile and molecular epidemiology of CR-PA over time is scarce. Thus, we conducted a cross-sectional analysis to investigate the phenotypic and genotypic characteristics of CR-PA recovered over different time periods, focusing on the isolates exhibiting a ceftolozane/tazobactam resistance phenotype. Methods: A total of 169 CR-PA isolated from clinical specimens at a single centre in Houston, TX, USA were studied. Among them, 61 isolates collected between 1999 and 2005 were defined as historical strains, and 108 collected between 2017 and 2018 were defined as contemporary strains. Antimicrobial susceptibilities against selected ß-lactams was determined. WGS data were used for the identification of antimicrobial resistance determinants and phylogenetic analysis. Results: Non-susceptibility to ceftolozane/tazobactam and ceftazidime/avibactam increased from 2% (1/59) to 17% (18/108) and from 7% (4/59) to 17% (18/108) from the historical to the contemporary collection, respectively. Carbapenemase genes, which were not identified in the historical collection, were harboured by 4.6% (5/108) of the contemporary strains, and the prevalence of ESBL genes also increased from 3.3% (2/61) to 16% (17/108). Genes encoding acquired ß-lactamases were largely confined to the high-risk clones. Among ceftolozane/tazobactam-resistant isolates, non-susceptibility to ceftazidime/avibactam, imipenem/relebactam and cefiderocol was observed in 94% (15/16), 56% (9/16) and 12.5% (2/16), respectively. Resistance to ceftolozane/tazobactam and imipenem/relebactam was primarily associated with the presence of exogenous ß-lactamases. Conclusions: Acquisition of exogenous carbapenemases and ESBLs may be a worrisome trend in P. aeruginosa.

Clinical Epidemiology and Antimicrobial Resistance Patterns of Infections Due to Salmonella Species in Children, Houston, TX. 2016-2021: A Retrospective Study.

BACKGROUND: Salmonellosis continues to be a major public health issue and high rates of infection are reported among young children. The contemporary clinical epidemiology of pediatric Salmonella spp. infections in the US is not well characterized. METHODS: We performed a retrospective observational study in a large hospital network in Houston, TX. We included all patients 18 years or younger identified as having a positive culture for Salmonella spp. from any body site during the years 2016-2021. The patient's medical record was accessed and detailed demographic, clinical and microbiologic information were collected. RESULTS: We identified a total of 110 pediatric patients with Salmonella spp. infections between 2016 and 2021. The highest frequency (69%) of infections was observed among children 0-5 years old. Bloody diarrhea was most frequently reported for children 0-1 years old. Although the highest number of salmonellosis was among infants smaller than 1 year, the percentage of bacteremia in this age group was the lowest (15%). Serotype Infantis was the most common (21%) and was less likely to cause Salmonella bacteremia. Among the Salmonella spp. isolates that had antimicrobial susceptibility performed 5 showed resistance to one or more antibiotics including 1 extensively drug-resistant S . ser. Typhi originating from Pakistan. CONCLUSION: Our findings suggest distinct clinical characteristics of Salmonella infections in the pediatric population. Consistent identification of isolates to the sub-species level along with serotyping seems critical to identify emerging lineages with increased virulence. Special consideration should be given to empiric treatment for patients who have recently returned from the Indian subcontinent.

Recognizing a MIS-Chievous Cause of Acute Viral Gastroenteritis.

Historically, children evaluated for vomiting and diarrhea secondary to viral enteritis have symptoms lasting 2-4 days and respond to supportive care, including oral rehydration and anti-emetics if required. Recently, within a 14-day timespan, we encountered three children with severe diarrhea who rapidly became dehydrated and went into hypotensive shock. Although SARS-CoV-2 molecular tests were negative by nasopharyngeal swab, all were later found to have MIS-C. This small case series underscores features reported in previous larger studies and emphasizes the rapid clinical evolution of this condition. We highlight the importance of early recognition of cardinal laboratory findings characteristic of MIS-C (i.e., lymphopenia, markedly elevated acute phase reactants, and hypoalbuminemia). We also show serologic evidence that the pathophysiological mechanism of SARS-CoV-2 related diarrhea may differ from other causes of dehydrating vomiting and diarrhea, with no serologic evidence of villus cell injury.

Lymphatic Dissemination and Axillary Web Syndrome in Primary Cutaneous Tuberculosis Secondary to Needlestick Injury.

Cutaneous tuberculosis secondary to skin inoculation of Mycobacterium tuberculosis is uncommon but it can occur in the health care settings. Herein, we report an unusual case of primary cutaneous tuberculosis of the thumb following a needlestick injury. The infection progressed with a necrotic granuloma, lymphatic dysfunction as visualized by near-infrared fluorescence lymphatic imaging, and the development of an axillary web syndrome.

Successful implementation of the CDC recommendations during the care of 2 patients with Candida auris in in-patient rehabilitation and intensive care settings.

Candida auris presents a unique challenge to practitioners and infection control teams worldwide because of its virulence, alarming resistance profile, environmental fitness, and risk of nosocomial transmission. We describe 2 cases of Candida auris infection managed with the CDC recommendations with no evidence of in-hospital transmission.

Screening donors for COVID-19 convalescent plasma.

BACKGROUND: Convalescent plasma is used as a treatment for COVID-19. Only limited data describe the efforts to recruit COVID-19 convalescent plasma (CCP) donors. We describe our experience engaging persons recovered from COVID-19 to donate CCP. STUDY DESIGN AND METHODS: We performed a retrospective analysis of the CCP recruitment for an 11-hospital health system in Houston, Texas. We sought CCP donations from: a) "volunteers" responding to advertisements in social media, press releases, and websites and b) "referred" individuals directed to the program or identified from hospitalization records. We determined the proportions of donor candidates who passed initial telephone health screening, who qualified after diagnostic testing, who presented to the regional CCP donation center, and who completed CCP donation. RESULTS: There were 900 CCP donor candidates, including 363 volunteers and 537 referred donors. Of 360 contacted volunteers, 186 (5.7%) were excluded by interview; 133 were referred for additional diagnostic screening, 97 completed donor antibody and antigen testing, and 87 were qualified for CCP donation, resulting in 35 CCP donations (9.7% of initial telephone contacts). Among 533 referred donors, 448 (84.1%) were excluded by interview, 71 were referred for additional screening, 48 completed donor antibody and antigen testing, and 40 were qualified for CCP donation, resulting in one CCP donation (0.2% of initial telephone contacts). CONCLUSION: In this community, screening of a high number of candidates yielded a limited number of CCP donations. These observations have important implications for CCP donor recruitment and community pandemic planning.

Simultaneous Infection with Enterobacteriaceae and Pseudomonas aeruginosa Harboring Multiple Carbapenemases in a Returning Traveler Colonized with Candida auris.

We report our clinical experience treating a critically ill patient with polymicrobial infections due to multidrug-resistant Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa in a 56-year-old woman who received health care in India and was also colonized by Candida auris A precision medicine approach using whole-genome sequencing revealed a multiplicity of mobile elements associated with NDM-1, NDM-5, and OXA-181 and, supplemented with susceptibility testing, guided the selection of rational antimicrobial therapy.

Long-Term Compassionate Use of Cefiderocol To Treat Chronic Osteomyelitis Caused by Extensively Drug-Resistant Pseudomonas aeruginosa and Extended-Spectrum-ß-Lactamase-Producing Klebsiella pneumoniae in a Pediatric Patient.

We report a 15 year-old Nigerian adolescent male with chronic osteomyelitis caused by an extensively drug-resistant (XDR) Pseudomonas aeruginosa strain of sequence type 773 (ST773) carrying blaNDM-1 and an extended spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae strain. The patient developed neurological side effects in the form of circumoral paresthesia with polymyxin B and asymptomatic elevation of transaminases with aztreonam (used in combination with ceftazidime-avibactam). Cefiderocol treatment for 14 weeks plus bone implantation resulted in apparent cure and avoided amputation.

What the Clinical Microbiologist Should Know About Pharmacokinetics/Pharmacodynamics in the Era of Emerging Multidrug Resistance: Focusing on ß-Lactam/ß-Lactamase Inhibitor Combinations.

As a class, ß-lactamase inhibitors have proved successful in extending the clinical utility of ß-lactam antibiotics by circumventing ß-lactamase-mediated resistance. However, the rapid evolution of these ß-lactamases calls for a critical reevaluation of the relationships between susceptibility, drug exposures, and bacterial response. The existing paradigm for in vitro susceptibility testing and development of ß-lactam/ß-lactamase inhibitor combinations may not optimally facilitate clinical use. Thus, alternative approaches for pairing these combinations and evaluating in vitro susceptibility are needed to provide better guidance to clinicians.

Extensively Drug-Resistant Pseudomonas aeruginosa ST309 Harboring Tandem Guiana Extended Spectrum ß-Lactamase Enzymes: A Newly Emerging Threat in the United States.

BACKGROUND: Treatment of serious infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa remains a challenge, despite the introduction of novel therapeutics. In this study, we report 2 extensively drug-resistant clinical isolates of sequence type (ST) 309 P aeruginosa resistant to all ß-lactams, including the novel combinations ceftolozane/tazobactam, ceftazidime/avibactam, and meropenem/vaborbactam. METHODS: Isolates were sequenced using both short-read (Illumina) and long-read technology to identify resistance determinants, polymorphisms (compared with P aeruginosa PAO1), and reconstruct a phylogenetic tree. A pair of ß-lactamases, Guiana extended spectrum ß-lactamase (GES)-19 and GES-26, were cloned and expressed in a laboratory strain of Escherichia coli to examine their relative impact on resistance. Using cell lysates from E coli expressing the GES genes individually and in tandem, we determined relative rates of hydrolysis for nitrocefin and ceftazidime. RESULTS: Two ST309 P aeruginosa clinical isolates were found to harbor the extended spectrum ß-lactamases GES-19 and GES-26 clustered in tandem on a chromosomal class 1 integron. The presence of both enzymes in E coli was associated with significantly elevated minimum inhibitory concentrations to aztreonam, cefepime, meropenem, ceftazidime/avibactam, and ceftolozane/tazobactam, compared with those expressed individually. The combination of ceftazidime/avibactam plus aztreonam was active in vitro and used to achieve cure in one patient. Phylogenetic analysis revealed ST309 P aeruginosa are closely related to MDR strains from Mexico also carrying tandem GES. CONCLUSIONS: The presence of tandem GES-19 and GES-26 is associated with resistance to all ß-lactams, including ceftolozane/tazobactam. Phylogenetic analysis suggests that ST309 P aeruginosa may be an emerging threat in the United States.

A case of Brucella aortitis associated with development of thoracic aortic aneurysm and aortobronchial fistula.

OBJECTIVES: The purpose of this case report is to document the occurrence of granulomatous aortitis complicated by formation of a saccular aneurysm and aortobronchial fistula due to Brucella infection. METHODS: A 65-year-old man with a history of feral swine hunting presented with hemoptysis and was found to have a saccular thoracic aortic aneurysm and associated aortobronchial fistula. The aneurysm underwent operative repair with closure of the aortobronchial fistula. RESULTS: Histopathological examination of the aneurysm wall revealed evidence of granulomatous aortitis. Cultures of the blood and aortic wall tissue were positive for Brucella suis. CONCLUSIONS: Although rare, Brucella infection should be considered in the differential diagnosis of aortic aneurysm with granulomatous aortitis.

In Vitro Evaluation of BacT/Alert FA Blood Culture Bottles and T2Candida Assay for Detection of Candida in the Presence of Antifungals.

The T2Candida assay is a novel, non-culture-based assay for the diagnosis of candidemia directly from whole blood. The impact of antifungals on the performance of the T2Candida assay and blood culture bottles has not been well described. In this study, the performance of the T2Candida assay was compared to that of blood culture in detecting Candida spp. in spiked blood cultures with or without the presence of antifungals. Clinical bloodstream isolates of Candida spp. were inoculated into human whole blood at low (1 to 5 cells/ml) and high (10 to 50 cells/ml) concentrations with or without the presence of caspofungin and fluconazole. Time to detection (TTD) was assessed for prepared samples using BacT/Alert FA aerobic blood culture bottles or the T2Candida assay. In the absence of antifungals, T2Candida assay sensitivity was comparable to that of blood culture at both the low inoculum and the high inoculum (95% versus 97.5% and 100% versus 100%, respectively) and the assay had an average TTD that was significantly shorter (5.1 h versus 27.2 to 30 h, respectively). Neither caspofungin nor fluconazole was observed to impact the sensitivity or TTD of the T2Candida assay, while fluconazole reduced the overall blood culture sensitivity by 7.5% to 12.5% (at the low inoculum and high inoculum, respectively) and significantly increased the TTD of Candida albicans, C. tropicalis, and C. parapsilosis by 14.8 to 67 h. Neither caspofungin nor fluconazole impacted the performance of the T2Candida assay in vitro, and the assay may be useful for the diagnosis of candidemia in patients receiving antifungal therapy.

Clinical Outcomes in Patients With Gram-Negative Infections Treated With Optimized Dosing Cefepime Over Various Minimum Inhibitory Concentrations.

BACKGROUND: The Clinical and Laboratory Standards Institute (CLSI) revised cefepime interpretive criteria, introducing the susceptible dose-dependent category for Enterobacteriaceae with a minimum inhibitory concentration (MIC) of 4 to 8 µg/mL in 2014. Limited clinical data support these new categories. This study compares outcomes of patients treated with standard and high-dose cefepime across various MICs. METHODS: We retrospectively reviewed cases of pneumonia or bacteremia caused by gram-negative organisms treated with adequate doses of cefepime for ≥48 hours. Outcomes were compared for MICs of ≤2 (low), 4 (medium), and 8 µg/mL (high). The primary end point was clinical failure, the secondary end point was microbiological failure. RESULTS: Ninety cases met the inclusion criteria: 46, 25, and 19 patients with low, medium, or high MIC, respectively. Multivariate logistic regression revealed that the medium (odds ratio [OR]: 9.13, P < .01) and high (OR: 6.79, P = .01) MIC groups had increased clinical failure. CONCLUSION: Cefepime therapy, even at CLSI-recommended doses, had an increased risk of clinical failure for gram-negative pathogens with MICs of 4 or 8 µg/mL. This finding suggests that higher dosing regimens (2 g every 8 hours or 1 g every 6 hours) may be necessary to treat serious gram-negative infections with elevated MICs.

Multicenter Evaluation of Ceftolozane/Tazobactam for Serious Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa.

A multicenter, retrospective study of patients infected with carbapenem-resistant Pseudomonas aeruginosa who were treated with ceftolozane/tazobactam was performed. Among 35 patients, pneumonia was the most common indication and treatment was successful in 26 (74%). Treatment failure was observed in all cases where isolates demonstrated ceftolozane-tazobactam minimum inhibitory concentrations ≥8 µg/mL.

Ceftaroline-Resistant, Daptomycin-Tolerant, and Heterogeneous Vancomycin-Intermediate Methicillin-Resistant Staphylococcus aureus Causing Infective Endocarditis.

We report a case of infective endocarditis (IE) caused by ceftaroline-resistant, daptomycin-tolerant, and heterogeneous vancomycin-intermediate methicillin-resistant S. aureus (MRSA). Resistance to ceftaroline emerged in the absence of drug exposure, and the E447K substitution in the active site of PBP2a previously associated with ceftaroline resistance was identified. Additionally, we present evidence of patient-to-patient transmission of the strain within the same unit. This case illustrates the difficulties in treating MRSA IE in the setting of a multidrug-resistant phenotype.

Association of pellicle growth morphological characteristics and clinical presentation of Mycobacterium tuberculosis isolates.

Trehalose 6,6'dimycolate (TDM) is a glycolipid found in nearly pure form on the surface of virulent Mycobacterium tuberculosis (MTB). This manuscript investigated the production of TDM, growth rate and colony morphology of multiple strains of MTB, each of which had been isolated from both pulmonary (sputum) and extrapulmonary sites of multiple patients. Since sputum contains MTB primarily from cavities and extrapulmonary biopsies are typically granulomas, this provided an opportunity to compare the behavior of single strains of MTB that had been isolated from cavities and granulomas. The results demonstrated that MTB isolated from pulmonary sites produced more TDM (3.23 ± 1.75 µg TDM/mg MTB), grew more rapidly as thin spreading pellicles, demonstrated early cording, and climbed culture well walls. In contrast, extrapulmonary isolates produced less TDM (1.42 ± 0.58 µg TDM/mg MTB) (p < 0.001) and grew as discrete patches with little tendency to spread or climb. Both Beijing pulmonary isolates and the non-Beijing pulmonary isolates produced significantly more TDM (1.64 ± 0.46 µg TDM/mg MTB) and grew faster than the Beijing and non-Beijing extrapulmonary isolates (1.14 ± 0.63 µg TDM/mg MTB) (p < 0.001 and p < 0.005 respectively). These results indicate that MTB from pulmonary sites (cavities) grows faster and produces more TDM than strains isolated from extrapulmonary sites (granulomas). This report suggests a critical role for TDM in cavitary TB.