Fatal borealpox in an immunosuppressed patient treated with antivirals and vaccinia immunoglobulin - Alaska, 2023.

BACKGROUND: Borealpox virus (BRPV, formerly known as Alaskapox virus) is a zoonotic member of the Orthopoxvirus genus first identified in a person in 2015. In the six patients with infection previously observed BRPV involved mild, self-limiting illness. We report the first fatal BRPV infection in an immunosuppressed patient. METHODS: A man aged 69 years from Alaska's Kenai Peninsula was receiving anti-CD20 therapy for chronic lymphocytic leukemia. He presented to care for a tender, red papule in his right axilla with increasing induration and pain. The patient failed to respond to multiple prescribed antibiotic regimens and was hospitalized 65 days postsymptom onset for progression of presumed infectious cellulitis. BRPV was eventually detected through orthopoxvirus real-time polymerase chain reaction testing of mucosal swabs. He received combination antiviral therapy, including 21 days of intravenous tecovirimat, intravenous vaccinia immunoglobulin, and oral brincidofovir. Serial serology was conducted on specimens obtained posttreatment initiation. FINDINGS: The patient's condition initially improved with plaque recession, reduced erythema, and epithelization around the axillary lesion beginning one-week post-therapy. He later exhibited delayed wound healing, malnutrition, acute renal failure, and respiratory failure. He died 138 days postsymptom onset. Serologic testing revealed no evidence the patient generated a humoral immune response. No secondary cases were detected. CONCLUSION: This report demonstrates that BRPV can cause overwhelming disseminated infection in certain immunocompromised patients. Based on the patient's initial response, early BRPV identification and antiviral therapies might have been beneficial. These therapies, in combination with optimized immune function, should be considered for patients at risk for manifestations of BRPV.

Identification of a Novel Mycoplasma Species in a Patient With Septic Arthritis of the Hip and Seal Finger.

An Alaska Native hunter developed fever, swollen finger, and septic hips after harvesting seals. Evaluation of hip tissue by 16S rRNA gene polymerase chain reaction and sequencing revealed a putative novel mycoplasma species. We report the identification of this organism and describe the first known case of disseminated seal finger mycoplasmosis.

An inconspicuous identification: Isolation and identification of a novel Pichia species presenting as fungemia following cardiac surgery.

Fungemia is common in critically ill patient populations, and is associated with a high rate of mortality, especially when caused by nonalbicans Candida species. Herein, we describe a fatal case of fungemia following cardiothoracic surgery in which the organism, initially identified as Candida inconspicua, represents a novel species: Pichia alaskaensis.

Transfusion-transmitted anaplasmosis from leukoreduced red blood cells.

BACKGROUND: Human granulocytic anaplasmosis (HGA) is a tick-borne rickettsial infectious disease. To date four cases of transfusion-transmitted anaplasmosis (TTA) have been described in the literature, and only one from leukoreduced red blood cells (RBCs). CASE REPORT: A 64-year-old patient with acute gastrointestinal blood loss was admitted to the hospital and received 5 units of prestorage leukoreduced RBCs. He was stabilized and discharged. He developed headache, fever, and chills 2 days after discharge and was readmitted. On Day 5 of his second admission polymorphonuclear leukocytes containing morulae consistent with HGA were reported in the peripheral smear. RESULTS: Samples from the recipient tested positive by polymerase chain reaction (PCR) for Anaplasma phagocytophilum, the causative agent of HGA and a segment from one of the five donors tested positive by both serology and PCR. CONCLUSION: Leukoreduction theoretically reduces the risk of TTA but does not interdict all infections. TTA requires consideration in recipients of RBC transfusion with unexplained fever.

Congenital toxoplasmosis presenting with fetal atrial flutter after maternal ingestion of infected moose meat.

Consumption of undercooked game meat during pregnancy is considered a risk factor for congenital toxoplasmosis, but cases definitively linking ingestion of infected meat to clinical disease are lacking. We report a confirmed case of congenital toxoplasmosis identified because of atrial flutter in the fetus and linked to maternal consumption of Toxoplasma gondii PCR-positive moose meat.

Prediction of treatment failure using 2010 World Health Organization Guidelines is associated with high misclassification rates and drug resistance among HIV-infected Cambodian children.

BACKGROUND: Antiretroviral therapy (ART) in resource-limited settings (RLSs) is monitored clinically and immunologically, according to World Health Organization (WHO) or national guidelines. Revised WHO pediatric guidelines were published in 2010, but their ability to accurately identify virological failure is unclear. METHODS: We evaluated performance of WHO 2010 guidelines and compared them with WHO 2006 and Cambodia 2011 guidelines among children on ≥6 months of first-line ART at Angkor Hospital for Children between January 2005 and September 2010. We determined sensitivity, specificity, positive and negative predictive values, and accuracy using bootstrap resampling to account for multiple tests per child. Human immunodeficiency virus (HIV) resistance was compared between those correctly and incorrectly identified by each guideline. RESULTS: Among 457 children with 1079 viral loads (VLs), 20% had >400 copies/mL. For children with WHO stage 1/2 HIV, misclassification as failure (met CD4 failure criteria, but VL undetectable) was 64% for WHO 2006 guidelines, 33% for WHO 2010 guidelines, and 81% for Cambodia 2011 guidelines; misclassification as success (did not meet CD4 failure, but VL detectable) was 11%, 12%, and 12%, respectively. For children with WHO stage 3/4 HIV, misclassification as failure was 35% for WHO 2006 guidelines, 40% for WHO 2010 guidelines, and 43% for Cambodia 2011 guidelines; misclassification as success was 13%, 24%, and 21%, respectively. Compared with WHO 2006 guidelines, WHO 2010 guidelines significantly increased the risk of misclassification as success in stage 3/4 HIV (P < .05). The WHO 2010 guidelines failed to identify 98% of children with extensive reverse-transcriptase resistance. CONCLUSIONS: In our cohort, lack of virological monitoring would result in unacceptable treatment failure misclassification, leading to premature ART switch and resistance accumulation. Affordable virological monitoring suitable for use in RLSs is desperately needed.

Falsely elevated vancomycin-concentration values from enzyme immunoassay leading to treatment failure.

PURPOSE: A case of vancomycin enzyme immunoassay (EIA) interference confirmed by high-performance liquid chromatography (HPLC) is described. SUMMARY: Therapeutic drug monitoring is standard of practice in vancomycin dosing and monitoring in order to maximize the pharmacodynamic effects and minimize toxicity. After a 52-year-old woman received 5 doses of vancomycin, serum concentrations continued to rise for several days in the absence of ongoing vancomycin administration. Despite persistently elevated vancomycin concentrations, the patient clinically deteriorated and required treatment with an alternative agent. Subsequently, serum concentrations were processed via HPLC and analyzed for percent protein binding. Confirmatory analysis revealed substantially lower concentrations by HPLC than were obtained by EIA and an abnormal elevation in protein binding. After discharge from the index admission, the patient returned 11 months later and had a dectectable vancomycin concentration by EIA prior to receipt of vancomycin. HPLC analysis confirmed the true concentration was undetectable. Though the exact interfering substance was not identified, the above discrepancy in concentrations between the two assay methods indicates the presence of assay interference, and adds to the available literature suggesting similar occurrences. This case is particularly troubling given that the level of interference was not such that it would lead a clinician to immediately suspect interference, and the patient experienced treatment failure. CONCLUSION: Falsely elevated values for serum vancomycin concentration, measured by EIA, contributed to treatment failure in a patient. The substance presumably responsible for EIA interferences was not identified.

Method to the madness: Impact of method of contact on intervention acceptance rates for antimicrobial stewardship interventions.

We retrospectively evaluated antimicrobial stewardship program (ASP) interventions over a 63-month period. We compared acceptance rates for those interventions communicated telephonically versus those communicated with a temporary note left in the electronic medical record. Telephonic communication produced superior acceptance rates overall and when analyzed by intervention type and provider.

Impact of an antimicrobial stewardship program on outcomes in patients with community-acquired pneumonia admitted to a tertiary community hospital.

PURPOSE: Results of a study evaluating the impact of an antimicrobial stewardship program (ASP) on clinical outcomes in patients hospitalized for community-acquired pneumonia (CAP) are reported. METHODS: A retrospective records review was conducted at a 400-bed hospital to identify patients admitted over 3 years with CAP documented as a primary or secondary diagnosis. Clinical and medication-use outcomes during a 1-year baseline period and in the first and second years after ASP implementation (post-ASP years 1 and 2) were analyzed. A local CAP guideline was implemented around the beginning of post-ASP year 2. RESULTS: The mean hospital length of stay declined from 7.24 days in the baseline period to 5.71 days in post-ASP year 1 (p = 0.011) and 5.52 days in post-ASP year 2 (p = 0.008). Mean inpatient antimicrobial days of therapy (DOT) declined from 5.68 days in the baseline period to 5.08 days (p = 0.045) and 4.99 days (p = 0.030) in post-ASP years 1 and 2, respectively. Mean DOT per 100 total days of antimicrobial therapy declined from 9.69 days in the baseline period to 8.85 days in post-ASP year 1 (p = 0.019) and 8.38 days in post-ASP year 2 (p = 0.001). CONCLUSION: ASP implementation was associated with specific clinical benefits in patients with CAP, including decreased length of stay, decreased durations of antimicrobial therapy, and a shift in utilization to a primary regimen shown to produce superior clinical outcomes.

Extensive drug resistance in HIV-infected Cambodian children who are undetected as failing first-line antiretroviral therapy by WHO 2010 guidelines.

Antiretroviral therapy in resource-limited settings is monitored clinically and immunologically according to WHO guidelines. Frequent misclassification of virologic failure is reported, mostly in adults, leading to early therapy switch or late failure diagnosis. Pediatric treatment monitoring and resistance data upon first-line failure are limited, particularly when the 2010-WHO pediatric guidelines are used without routine viral load monitoring. We previously reported high treatment failure misclassification rates by pediatric 2010 guidelines in Cambodian children on first-line therapy. Here we determine the extent and patterns of resistance, with yearly viral load and 6-monthly CD4. Drug resistance mutations were determined using the IAS-USA 2011 list. Predicted resistance interpretation was determined with Stanford Database tools. Fifty-one children with available genotypes met inclusion criteria. All but one (subtype B) were CRF01_AE. The most common regimen was stavudine, lamivudine, and nevirapine (96%), taken for a median of 2.2 years. Resistance was seen in 98%; 96% to nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs); 51% with ≥4 mutations. The most common NRTI mutations were 184V/I and 67N and the most common NNRTI mutations were 181C/Y/I/V and 190A/S. A total of 22% had multiresistant mutations and 18% had predicted high-level resistance to subsequent therapy options didanosine, abacavir, etravirine, and tenofovir. In 98% of Cambodian children misclassified as nonfailing first-line therapy by 2010 guidelines, 51% had extensive drug resistance to current and 18% to subsequent antiretroviral therapy. Affordable routine viral load monitoring allowing for early and more accurate treatment failure diagnosis is desperately needed in resource-limited settings.