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ImportancePregnant women are at increased risk of severe COVID-19, but the contribution of viral RNA load, the presence of infectious virus, and mucosal antibody responses remain understudied.ObjectiveTo evaluate the association of COVID-19 outcomes following confirmed infection with vaccination status, mucosal antibody responses, infectious virus recovery and viral RNA levels in pregnant compared with non-pregnant women.DesignA retrospective observational cohort study of remnant clinical specimens from SARS-CoV-2 infected patients between October 2020-May 2022.SettingFive acute care hospitals within the Johns Hopkins Health System (JHHS) in the Baltimore, MD-Washington, DC area.ParticipantsParticipants included confirmed SARS-CoV-2 infected pregnant women and matched non-pregnant women (matching criteria included age, race/ethnicity, and vaccination status).ExposureSARS-CoV-2 infection, with documentation of SARS-CoV-2 mRNA vaccination.Main Outcome(s)The primary dependent measures were clinical COVID-19 outcomes, infectious virus recovery, viral RNA levels, and mucosal anti-spike (S) IgG titers from upper respiratory tract samples. Clinical outcomes were compared using odds ratios (OR), and measures of virus and antibody were compared using either Fisher’s exact test, two-way ANOVA, or regression analyses. Results were stratified according to pregnancy, vaccination status, maternal age, trimester of pregnancy, and infecting SARS-CoV-2 variant.Results(s)A total of 452 individuals (117 pregnant and 335 non-pregnant) were included in the study, with both vaccinated and unvaccinated individuals represented. Pregnant women were at increased risk of hospitalization (OR = 4.2; CI = 2.0-8.6), ICU admittance, (OR = 4.5; CI = 1.2-14.2), and of being placed on supplemental oxygen therapy (OR = 3.1; CI =1.3-6.9). An age-associated decrease in anti-S IgG titer and corresponding increase in viral RNA levels (P< 0.001) was observed in vaccinated pregnant, but not non-pregnant, women. Individuals in their 3rdtrimester had higher anti-S IgG titers and lower viral RNA levels (P< 0.05) than those in their 1stor 2ndtrimesters. Pregnant individuals experiencing breakthrough infections due to the omicron variant had reduced anti-S IgG compared to non-pregnant women (P< 0.05).Conclusions and RelevanceIn this cohort study, vaccination status, maternal age, trimester of pregnancy, and infecting SARS-CoV-2 variant were each identified as drivers of differences in mucosal anti-S IgG responses in pregnant compared with non-pregnant women. Observed increased severity of COVID-19 and reduced mucosal antibody responses particularly among pregnant participants infected with the Omicron variant suggest that maintaining high levels of SARS-CoV-2 immunity may be important for protection of this at-risk population.Key PointsQuestionIs greater COVID-19 disease severity during pregnancy associated with either reduced mucosal antibody responses to SARS-CoV-2 or increased viral RNA levels?FindingIn a retrospective cohort of pregnant and non-pregnant women with confirmed SARS-CoV-2 infection, we observed that (1) disease severity, including ICU admission, was greater among pregnant than non-pregnant women; (2) vaccination was associated with reduced recovery of infectious virus in non-pregnant women but not in pregnant women; (3) increased nasopharyngeal viral RNA levels were associated with reduced mucosal IgG antibody responses in pregnant women; and (4) greater maternal age was associated with reduced mucosal IgG responses and increased viral RNA levels, especially among women infected with the Omicron variant.MeaningThe findings of this study provide novel evidence that, during pregnancy, lower mucosal antibody responses are associated with reduced control of SARS-CoV-2, including variants of concern, and greater disease severity, especially with increasing maternal age. Reduced mucosal antibody responses among vaccinated pregnant women highlight the need for bivalent booster doses during pregnancy.

Docetaxel is a microtubule inhibitor indicated for the treatment of multiple cancers as a single agent or in combination with other antineoplastics. The U.S. Food and Drug Administration (FDA) conducted a postmarketing review of fatal neutropenic enterocolitis cases reported with docetaxel using the FDA Adverse Event Reporting System (FAERS) and literature to determine whether the drug was a potential cause. We searched FAERS and the literature for reports of fatal neutropenic enterocolitis with docetaxel-based treatment reported between 14 May 1996 and 13 March 2017. We characterized the clinical course and severity of neutropenic enterocolitis and utilized the World Health Organization-Uppsala Monitoring Centre rubric to assess drug causality. We identified 41 fatal cases of neutropenic enterocolitis with docetaxel from FAERS and the literature. The median time to onset of neutropenic enterocolitis from last docetaxel dose was seven days (range 2–13 days), and median time to death was nine days (range 3–23 days). The cause of death in 83% (34/41) of patients was neutropenic enterocolitis. We determined the drug-event association as probable in seven cases. Neutropenic enterocolitis with docetaxel monotherapy occurred in six cases; however, in 85% (35/41) of cases, neutropenic enterocolitis occurred when docetaxel was used in combination with other cytotoxic chemotherapy. In some cases, neutropenic enterocolitis occurred despite use of granulocyte colony-stimulating factors. Neutropenic enterocolitis is a severe and potentially fatal complication of docetaxel-based treatment, especially when combined with other antineoplastic treatments known to cause neutropenia. Practitioners should be aware of this safety risk to promptly recognize and manage patients.

Summary Background Non-meningococcal, non-gonococcal Neisseria spp. are typically commensal and rarely cause invasive disease. Eculizumab is a terminal complement inhibitor that increases susceptibility to meningococcal disease, but data on disease caused by typically-commensal Neisseria spp. are lacking. This series describes postmarketing reports of typically-commensal Neisseria spp. disease in patients receiving eculizumab. Methods We searched the FDA Adverse Event Reporting System (FAERS) and medical literature for reports of commensal Neisseria spp. disease in patients receiving eculizumab, from eculizumab U.S. approval (2007) through January 31, 2018. Results We identified seven FAERS reports (including one case also reported in the literature) of non-meningococcal, non-gonococcal Neisseria disease, including N. sicca (mucosa)/subflava (n = 2), N. cinerea (n = 2), N. sicca (mucosa) (n = 1), N. mucosa (n = 1, with concurrent alpha-hemolytic Streptococcus bacteremia), and N. flavescens (subflava) (n = 1). Four cases had sources of patient immunosuppression in addition to eculizumab. Three patients had sepsis (n = 2) or septic shock (n = 1). Five patients were bacteremic. All patients were hospitalized; the infections resolved with antibiotics. Conclusions Our search identified seven cases of disease from typically commensal Neisseria spp. in eculizumab recipients. These findings suggest that any Neisseria spp. identified from a normally sterile site in an eculizumab recipient could represent true infection warranting prompt treatment.

Background Gonorrhea is the second most commonly reported notifiable condition in the United States. Infrequently, Neisseria gonorrhoeae can cause disseminated gonococcal infection (DGI). Eculizumab, a monoclonal antibody, inhibits terminal complement activation, which impairs the ability of the immune system to respond effectively to Neisseria infections. This series describes cases of N. gonorrhoeae infection among patients receiving eculizumab. Methods Pre- and postmarketing safety reports of N. gonorrhoeae infection in patients receiving eculizumab worldwide were obtained from US Food and Drug Administration safety databases and the medical literature, including reports from the start of pivotal clinical trials in 2004 through 31 December 2017. Included patients had at least 1 eculizumab dose within the 3 months prior to N. gonorrhoeae infection. Results Nine cases of N. gonorrhoeae infection were identified; 8 were classified as disseminated (89%). Of the disseminated cases, 8 patients required hospitalization, 7 had positive blood cultures, and 2 required vasopressor support. One patient required mechanical ventilation. Neisseria gonorrhoeae may have contributed to complications prior to death in 1 patient; however, the fatality was attributed to underlying disease per the reporter. Conclusions Patients receiving eculizumab may be at higher risk for DGI than the general population. Prescribers are encouraged to educate patients receiving eculizumab on their risk for serious gonococcal infections and perform screening for sexually transmitted diseases (STDs) per the Centers for Disease Control and Prevention STD treatment guidelines or in suspected cases. If antimicrobial prophylaxis is used during eculizumab therapy, prescribers should consider trends in gonococcal antimicrobial susceptibility due to emerging resistance concerns.

Background Non-meningococcal and nongonococcal Neisseria spp. are usually commensal and rarely cause invasive disease in humans. Eculizumab, a terminal complement inhibitor, increases susceptibility to meningococcal disease, but data on atypical Neisseria spp. disease in persons receiving eculizumab are lacking. This case series describes postmarketing reports of disease by commensal Neisseria spp. in patients receiving eculizumab. Methods The FDA Adverse Event Reporting System (FAERS) database and the medical literature were searched for cases of disease by any nonmeningococcal and nongonococcal Neisseria spp. in patients receiving eculizumab. Included cases had a diagnosis of disease by any atypical Neisseria spp. with onset on or before January 31, 2018 and ≥1 dose of eculizumab in the 3 months prior to disease. Results The search identified seven FAERS cases, including one case also reported in the literature. Patient ages ranged from 4 to 38 years. Five patients had positive blood cultures, of which three had an indwelling catheter for vascular access (n = 2, N. sicca/subflava) or hemodialysis (n = 1, N. cinerea). Two patients with bacteremia had N. cinerea septic shock with possible cholecystitis, and N. mucosa sepsis with concurrent Streptococcus bacteremia after gastroenteritis. The remaining two cases in the series included one with N. sicca bacterial peritonitis associated with a peritoneal dialysis catheter (negative blood cultures, other cultures not specified), and one with a diagnosis of N. flavescens sepsis while neutropenic (specimen source not specified). All seven patients were hospitalized and three had sepsis or septic shock. All cases resolved with antibiotics and supportive care. Conclusion We identified seven cases of serious disease caused by atypical Neisseria spp. among eculizumab recipients. Since these organisms are typical inhabitants of the oropharynx and urogenital tract and are not skin flora, the source of disease was unclear. Our data suggest that eculizumab may confer increased risk for disease by usually commensal Neisseria spp. Healthcare professionals are encouraged to treat all Neisseria spp. isolated from sterile sites as pathogenic, and not as contaminants, in patients receiving eculizumab. Disclosures All authors: No reported disclosures.

Background Use of sodium-glucose cotransporter-2 (SGLT2) inhibitors has been associated with Fournier gangrene (FG), a rare urologic emergency characterized by necrotizing infection of the external genitalia, perineum, and perianal region. Objective To describe and compare reported cases of FG in diabetic adults receiving treatment with SGLT2 inhibitors or other antiglycemic agents. Design Descriptive case series. Setting U.S. Food and Drug Administration (FDA) Adverse Event Reporting System and published case reports. Patients Adults receiving SGLT2 inhibitors or other antiglycemic agents. Measurements Clinical and laboratory data. Results The FDA identified 55 unique cases of FG in patients receiving SGLT2 inhibitors between 1 March 2013 and 31 January 2019. The patients ranged in age from 33 to 87 years; 39 were men, and 16 were women. Time to onset after initiation of SGLT2-inhibitor therapy ranged from 5 days to 49 months. All patients had surgical debridement and were severely ill. Reported complications included diabetic ketoacidosis (n = 8), sepsis or septic shock (n = 9), and acute kidney injury (n = 4). Eight patients had fecal diversion surgery, 2 patients developed necrotizing fasciitis of a lower extremity that required amputation, and 1 patient required a lower-extremity bypass procedure because of gangrenous toes. Three patients died. For comparison, the FDA identified 19 FG cases associated with other antiglycemic agents between 1984 and 31 January 2019: metformin (n = 8), insulin glargine (n = 6), short-acting insulin (n = 2), sitagliptin plus metformin (n = 2), and dulaglutide (n = 1). These patients ranged in age from 42 to 79 years; 12 were men, and 7 were women. Two patients died. Limitation Inability to establish causality or incidence, variable quality of reports, possible underreporting, and confounding by indication. Conclusion FG is a newly identified safety concern in patients receiving SGLT2 inhibitors. Physicians prescribing these agents should be aware of this possible complication and have a high index of suspicion to recognize it in its early stages. Primary funding source None.

Direct-acting antiviral agents (DAAs) are used increasingly to treat hepatitis C virus (HCV) infection. Reports were published recently on hepatitis B virus (HBV) reactivation (HBV-R) in patients with HBV-HCV co-infection. Hepatitis B virus reactivation, defined as an abrupt increase in HBV replication in patients with inactive or resolved HBV infection, may result in clinically significant hepatitis.To assess whether HBV-R is a safety concern in patients receiving HCV DAAs.Descriptive case series.U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).29 patients with HBV-R receiving HCV DAAs.Clinical and laboratory data.The FDA identified 29 unique reports of HBV-R in patients receiving DAAs from 22 November 2013 to 15 October 2016. Two cases resulted in death and 1 case in liver transplantation. Patients in whom HBV-R developed were heterogeneous regarding HCV genotype, DAAs received, and baseline HBV characteristics. At baseline, 9 patients had a detectable HBV viral load, 7 had positive results on hepatitis B surface antigen (HBsAg) testing and had an undetectable HBV viral load, and 3 had negative results on HBsAg testing and had an undetectable HBV viral load. For the remaining 10 patients, data points were not reported or the data were uninterpretable. Despite provider knowledge of baseline HBV, HBV-R diagnosis and treatment were delayed in 7 cases and possibly 7 others.The quality of information varied among reports. Because reporting is voluntary, HBV-R associated with DAAs likely is underreported.Hepatitis B virus reactivation is a newly identified safety concern in patients with HBV-HCV co-infection treated with DAAs. Patients with a history of HBV require clinical monitoring while receiving DAA therapy. Studies would help determine the risk factors for HBV-R, define monitoring frequency, and identify patients who may benefit from HBV prophylaxis and treatment. DAAs remain a safe and highly effective treatment for the management of HCV infection.None.

Recent evidence suggests that sexually transmitted diseases (STDs) enhance the transmission of human immunodeficiency virus (HIV) type 1. In 143 HIV-infected women enrolled in a university-based longitudinal HIV clinic over 16 months (mean), the STD point prevalence was examined at enrollment and the cumulative prevalence was calculated at follow-up. At enrollment, 35 women (25%) had > or = 1 STD. These included trichomoniasis in 16 women (11%); syphilis, 9 (6%); genital herpes, 8 (6%); gonorrhea, 5 (4%); chlamydia, 5 (4%); genital warts, 2 (1%); and pelvic inflammatory disease (PID), 1 (1%). STDs were found in 55 (42%) of the 125 patients who returned for at least one follow-up visit: trichomoniasis in 23 (18%); genital herpes, 20 (12%); gonorrhea, 9 (7%); syphilis, 7 (6%); genital warts, 7 (6%); chlamydia, 5 (4%); and PID, 4 (3%). Despite counseling at both enrollment and follow-up, these women had a very high cumulative prevalence of STDs, indicating persistent high-risk sexual behavior.

Sexually transmitted diseases have the greatest impact on the health of women. They are frequently asymptomatic, so screening for infection is important in preventing the long-term sequelae which include infertility, ectopic pregnancy, and chronic pelvic pain. HIV continues to increase in the female population and the gynecologic complications associated with it are unique to this population. Use of zidovudine in pregnant HIV-infected women has substantially decreased the rate of vertical transmission of HIV infection. The epidemiologic synergy between HIV and STDs is well recognized and prevention of one is dependent on prevention of the other.

Botryomycosis is an uncommon bacterial disease characterized by the microscopic formation of eosinophilic granules that resemble those of infection by Actinomyces species. The diagnosis of botryomycosis can be made when microscopic inspection and culture of the granules reveal gram-positive cocci or gram-negative bacilli. Botryomycosis is caused by common bacterial pathogens including Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, yet the host and microbial factors that contribute to the pathobiology remain unknown. Pulmonary botryomycosis can resemble actinomycosis, tuberculosis, or invasive carcinoma by causing a mass lesion with constitutional symptoms. Radiographically, it invades bone and disrupts tissue planes. Successful treatment often requires a combination of both surgical debridement and long-term antimicrobial therapy. We report a case of primary pulmonary botryomycosis and review the literature on this unusual infectious process.

To better characterize the long-term effects of tenofovir on renal function in a large managed care organization.We performed a retrospective cohort analysis in Kaiser Permanente for years 2002 to 2005 comparing renal function among antiretroviral naïve patients initiating a tenofovir-containing regimen (964 patients) or tenofovir-sparing regimens (683 patients). We evaluated glomerular filtration rate (GFR, [Modification of Diet in Renal Disease equation]), serum creatinine, and the development of renal proximal tubular dysfunction. We report multivariable hazard ratios (HR, Cox modeling) and linear outcomes (repeated measures) with predictors retained if P0.10 (backward selection). Potential predictor variables included in multivariate models were age, sex, Black race, baseline laboratories (including CD4 count), history of diabetes mellitus, hypertension, malignancy, hepatitis, and concurrent medications.Overall, tenofovir-exposed patients had a larger relative decline in GFR through 104 weeks (-7.6 mL/min/1.73 m(2) relative to tenofovir-sparing, P0.001); the degree of the difference varied by baseline GFR, with the greatest effect seen in those patients with GFR greater than 80 mL/min/1.73 m(2). Tenofovir-exposed patients had greater development of proximal tubular dysfunction over time (at 52 wk: HR(adjusted) = 1.95 [P = 0.01] and at 104 wk: HR(adjusted) = 5.23 [P = 0.0004]) and had greater risk of medication discontinuation (HR(adjusted) = 1.21, P = 0.02), especially as renal function worsened. Viral control and CD4 count changes were similar between the two groups.Tenofovir is associated with greater effect on decline in renal function and a higher risk of proximal tubular dysfunction in antiretroviral naïve patients initiating antiretroviral therapy.

To determine the impact of depression on highly active antiretroviral therapy (HAART) adherence and clinical measures and investigate if selective serotonin reuptake inhibitors (SSRIs) improve these measures.Retrospective cohort study.In 2 large health maintenance organizations, we measured the effects of depression (with and without SSRI use) on adherence and changes in viral and immunologic control among HIV-infected patients starting a new HAART regimen. HAART adherence, HIV RNA levels, and changes in CD4 T-cell counts through 12 months were measured.A total of 3359 patients were evaluated; 42% had a depression diagnosis, and 15% used SSRIs during HAART. Depression without SSRI use was associated with significantly decreased odds of achievingor =90% adherence to HAART (odds ratio [OR] = 0.81, 95% confidence interval [CI]: 0.70 to 0.98; P = 0.03). Depression was associated with significantly lower odds of an HIV RNA level500 copies/mL (OR = 0.77, 95% CI: 0.62 to 0.95; P = 0.02). Depressed patients compliant with SSRI medication (80% adherence to SSRI) had HAART adherence and viral control statistically similar to nondepressed HIV-infected patients taking HAART. Comparing depressed with nondepressed HIV-infected patients, CD4 T-cell responses were statistically similar; among depressed patients, those compliant with SSRI had statistically greater increases in CD4 cell responses.Depression significantly worsens HAART adherence and HIV viral control. Compliant SSRI use is associated with improved HIV adherence and laboratory parameters.

The radiographic and computed tomographic (CT) findings in two patients with documented inhalational anthrax resulting from bioterrorism exposure are presented. Chest radiographs demonstrated mediastinal widening, adenopathy, pleural effusions, and air-space disease. Chest CT images revealed enlarged hyperattenuating mediastinal and hilar lymph nodes and edema of mediastinal fat. Chest CT findings are helpful for making the initial diagnosis. To the authors' knowledge, the spectrum and follow-up of CT findings have not been previously described.

Nevirapine is a nonnucleoside reverse transcriptase inhibitor (NNRTI) that has the most common treatment limiting side effect of rash. Severe rash has been observed in 3% of patients taking nevirapine in clinical trials, 85% of whom were men. In a multicenter, retrospective cohort study of all patients who received nevirapine over a 5-year period, severe rash was noted in 9 of 95 women and 3 of 263 men (risk ratio [RR], 8.31; 95% confidence interval [CI], 2.3-30.0; P=.005). Women were more likely to discontinue nevirapine therapy because of rash (RR, 4.5; 95% CI, 1. 9-10.5; P=.0005). After adjusting for age and baseline CD4 cell count in multivariate analysis, women had a 7-fold increase in risk for severe rash and were 3.5 times more likely to discontinue nevirapine therapy. In women of reproductive age for whom contraception may occur, nevirapine remains the NNRTI of choice. Recognition of sex differences in this severe adverse event will be important in prescribing nevirapine.