Adverse Events Associated With Treatment for Pan-Susceptible Tuberculosis in San Francisco.

Of 373 patients treated for drug-susceptible tuberculosis, 35.4% (46.2% aged ≥65 years) developed moderate/severe adverse events that required treatment interruption (34.8%), first-line drug discontinuation (26.2%, primarily pyrazinamide), second-line drug initiation (30.0%), and treatment duration up to 3.8 months longer. More safe and effective options are needed, including for the elderly.

Uniting for Ukraine Tuberculosis Screening Experience, San Francisco, California, USA.

Ukraine surveillance data suggest high tuberculosis (TB) incidence, including multidrug resistance. Of 299 newcomers from Ukraine screened in San Francisco, California, USA, by using an interferon-γ-release-assay (IGRA) and chest radiograph, 7.4% were IGRA positive and 1 had laboratory-confirmed pansusceptible TB. Screening with IGRA and chest radiograph can help characterize TB risk.

Lessons From Mass-Testing for Coronavirus Disease 2019 in Long-Term Care Facilities for the Elderly in San Francisco.

Coronavirus disease 2019 can cause significant mortality in the elderly in long-term care facilities (LTCF). We describe 4 LTCF outbreaks where mass testing identified a high proportion of asymptomatic infections (4%-41% in healthcare workers and 20%-75% in residents), indicating that symptom-based screening alone is insufficient for monitoring for COVID-19 transmission.

Tuberculosis-Associated Hospitalizations and Deaths after COVID-19 Shelter-In-Place, San Francisco, California, USA.

A mandated shelter-in-place and other restrictions associated with the coronavirus disease pandemic precipitated a decline in tuberculosis diagnoses in San Francisco, California, USA. Several months into the pandemic, severe illness resulting in hospitalization or death increased compared with prepandemic levels, warranting heightened vigilance for tuberculosis in at-risk populations.

Influenza-associated intensive-care unit admissions and deaths - California, September 29, 2013-January 18, 2014.

The California Department of Public Health (CDPH) conducts surveillance on severe influenza illness among California residents aged <65 years. Severe cases are defined as those resulting in admission to an intensive care unit (ICU) or death; reporting of ICU cases is voluntary, and reporting of fatal cases is mandatory. This report describes the epidemiologic, laboratory, and clinical characteristics of ICU and fatal influenza cases with symptom onset on or after September 29, 2013, and reported by January 18, 2014 of the 2013-14 influenza season. At the time of this report, local health jurisdictions (LHJs) in California had reported 94 deaths and 311 ICU admissions of patients with a positive influenza test result. The 405 reports of severe cases (i.e., fatal and ICU cases combined) were more than in any season since the 2009 pandemic caused by the influenza A (H1N1)pdm09 (pH1N1) virus. The pH1N1 virus is the predominant circulating influenza virus this season. Of 405 ICU and fatal influenza cases, 266 (66%) occurred among patients aged 41-64 years; 39 (10%) severe influenza illnesses occurred among children aged <18 years. Only six (21%) of 28 patients with fatal illness whose vaccination status was known had received 2013-14 seasonal influenza vaccine ≥2 weeks before symptom onset. Of 80 patients who died for whom sufficient information was available, 74 (93%) had underlying medical conditions known to increase the risk for severe influenza, as defined by the Advisory Committee on Immunization Practices (ACIP). Of 47 hospitalized patients with fatal illness and known symptom onset and antiviral therapy dates, only eight (17%) received neuraminidase inhibitors within 48 hours of symptom onset. This report supports previous recommendations that vaccination is important to prevent influenza virus infections that can result in ICU admission or death, particularly in high-risk populations, and that empiric antiviral treatment should be promptly initiated when influenza virus infection is suspected in hospitalized patients, despite negative results from rapid diagnostic tests.

Fatal meningococcal disease in a laboratory worker--California, 2012.

Occupationally acquired meningococcal disease is rare. Adherence to recommendations for safe handling of Neisseria meningitidis in the laboratory greatly reduces the risk for transmission to laboratory workers. A California microbiologist developed fatal serogroup B meningococcal disease after working with N. meningitidis patient isolates in a research laboratory (laboratory A). The California Department of Public Health (CDPH), the local health department, the California Division of Occupational Safety and Health (CalOSHA), and the federal Occupational Safety and Health Administration (OSHA) collaborated on an investigation of laboratory A, which revealed several breaches in recommended laboratory practice for safe handling of N. meningitidis, including manipulating cultures on the bench top. Additionally, laboratory workers had not been offered meningococcal vaccine in accordance with Advisory Committee on Immunization Practices (ACIP) recommendations and CalOSHA Aerosol Transmissible Diseases Standard requirements. In accordance with OSHA and CalOSHA regulations, laboratory staff members must receive laboratory biosafety training and use appropriate personal protective equipment, and those who routinely work with N. meningitidis isolates should receive meningococcal vaccine.

Experience With Four-Month Rifapentine and Moxifloxacin-Based Tuberculosis Treatment in San Francisco.

Background: A multicountry randomized controlled trial has demonstrated that pan-susceptible pulmonary tuberculosis (TB) can be successfully treated with a 4-month regimen of daily isoniazid, rifapentine, moxifloxacin, and pyrazinamide (HPMZ). We piloted HPMZ in San Francisco (SF) using a modified version of the US Centers for Disease Control and Prevention HPMZ treatment guidelines. Methods: In this retrospective cohort, patients consecutively referred to SF TB clinic were evaluated for HPMZ eligibility based on preestablished inclusion/exclusion criteria. All underwent evaluation and management according to national recommendations. We reviewed the medical records of those initiated on HPMZ. Results: From August 2021 to December 2023, 30 (18.8%) of 160 patients diagnosed with active TB met HPMZ inclusion criteria; of these, 22 (13.8%) started HPMZ. The median age (range) was 32.5 (14-86) years, 17 (77.3%) were otherwise healthy, and 19 (86.4%) had pulmonary TB, including 7 (36.8%) with cavitary disease. Eighteen (81.8%) patients had an adverse event, with 11 (50%) prematurely discontinuing HPMZ; the most common adverse events were vomiting, elevated transaminases, and rash. To date, 9 (40.9%) have completed treatment, with most achieving criteria for cure. One patient was diagnosed with possible TB recurrence and restarted standard TB treatment. Conclusions: Our experience, with half of patients to date prematurely discontinuing HPMZ, illustrates the challenge of extrapolating findings from TB clinical trials commonly conducted in high-incidence, non-US settings to US clinical practice. Further experience may help identify best practices for implementing HPMZ, including identifying predictors of which patients may be most likely to benefit from and tolerate this regimen.

A teenage girl with altered mental status and paraparesis.

A teenage girl presented with fever and altered mental status. MRI showed diffuse leptomeningeal enhancement of the brain and spine. She was diagnosed by a positive cerebrospinal fluid (CSF) culture with tuberculous (TB) meningitis and was started on anti-TB medications and corticosteroids. Her mental status improved, but she was noted to have proximal weakness of the lower extremities. In the course of tapering corticosteroids at week 11 of anti-TB therapy, she became acutely confused and febrile. MRI demonstrated interval development of tuberculomas in the brain and a mass lesion in the thoracic spine causing cord compression. Given the clinical picture was suggestive of a paradoxical reaction, the dose of corticosteroids was increased. Infliximab was added when repeat MRI revealed enlargement of the mass lesion in the spine with worsening cord compression. She was successfully tapered off of corticosteroids. Over several months, the patient's motor function recovered fully, and she returned to ambulating without assistance.

Severe 2009 H1N1 influenza in pregnant and postpartum women in California.

BACKGROUND: Like previous epidemic and pandemic diseases, 2009 pandemic influenza A (H1N1) may pose an increased risk of severe illness in pregnant women. METHODS: Statewide surveillance for patients who were hospitalized with or died from 2009 H1N1 influenza was initiated by the California Department of Public Health. We reviewed demographic and clinical data reported from April 23 through August 11, 2009, for all H1N1-infected, reproductive-age women who were hospitalized or died--nonpregnant women, pregnant women, and postpartum women (those who had delivered < or = 2 weeks previously). RESULTS: Data were reported for 94 pregnant women, 8 postpartum women, and 137 nonpregnant women of reproductive age who were hospitalized with 2009 H1N1 influenza. Rapid antigen tests were falsely negative in 38% of the patients tested (58 of 153). Most pregnant patients (89 of 94 [95%]) were in the second or third trimester, and approximately one third (32 of 93 [34%]) had established risk factors for complications from influenza other than pregnancy. As compared with early antiviral treatment (administered < or = 2 days after symptom onset) in pregnant women, later treatment was associated with admission to an intensive care unit (ICU) or death (relative risk, 4.3). In all, 18 pregnant women and 4 postpartum women (total, 22 of 102 [22%]) required intensive care, and 8 (8%) died. Six deliveries occurred in the ICU, including four emergency cesarean deliveries. The 2009 H1N1 influenza-specific maternal mortality ratio (the number of maternal deaths per 100,000 live births) was 4.3. CONCLUSIONS: 2009 H1N1 influenza can cause severe illness and death in pregnant and postpartum women; regardless of the results of rapid antigen testing, prompt evaluation and antiviral treatment of influenza-like illness should be considered in such women. The high cause-specific maternal mortality rate suggests that 2009 H1N1 influenza may increase the 2009 maternal mortality ratio in the United States.

A population-based study of neurologic manifestations of severe influenza A(H1N1)pdm09 in California.

BACKGROUND: Reported influenza-associated neurologic complications are generally limited to case series or case reports. We conducted a population-based study of neurologic manifestations associated with severe and fatal influenza A(H1N1)pdm09 (2009 H1N1) cases. METHODS: Medical records of patients with fatal or severe (hospitalized in intensive care unit) laboratory-confirmed 2009 H1N1 reported to the California Department of Public Health from 15 April 2009 through 31 December 2009 were reviewed to identify those with primary neurological manifestations. Cases with secondary neurologic manifestations (eg, hypoxia) were excluded. Primary influenza-associated neurologic complications (INCs) were classified into 4 groups: encephalopathy/encephalitis, seizures, meningitis, and other. Severe 2009 H1N1-associated neurologic incidence was calculated by using estimates of 2009 H1N1 illnesses in California. RESULTS: Of 2069 reported severe or fatal 2009 H1N1 cases, 419 (20%) had neurologic manifestations. Of these, 77 (18%) met our definition of INCs: encephalopathy/encephalitis (n = 29), seizures (n = 44), meningitis (n = 3), and other (Guillain-Barré Syndrome) (n = 1). The median age was 9 years (range, 4 months-92 years); the highest rate of disease was among pediatric Asian/Pacific Islanders (12.79 per 1,000,000) compared with pediatric white, non-Hispanics (3.09 per 1,000,000), Hispanics (4.58 per 1,000,000), and blacks (6.57 per 1,000,000). The median length of stay (LOS) was 4 days (range, 1-142), and there were 4 fatalities. The estimated incidence of INCs was 1.2 per 100,000 symptomatic 2009 H1N1 illnesses. CONCLUSIONS: Influenza-associated neurologic complications were observed in 4% of patients with fatal or severe 2009 H1N1. They were observed most often in pediatric patients, and Asian/Pacific Islanders appear to be overrepresented compared with the California population. Most patients with INCs had a relatively short LOS, and there were few fatalities.

Treatment with neuraminidase inhibitors for critically ill patients with influenza A (H1N1)pdm09.

BACKGROUND: Neuraminidase inhibitor (NAI) antiviral drugs can shorten the duration of uncomplicated influenza when administered early (<48 hours after illness onset) to otherwise healthy outpatients, but the optimal timing of effective therapy for critically ill patients is not well established. METHODS: We analyzed California surveillance data to characterize the outcomes of patients in intensive care units (ICUs) treated with NAIs for influenza A(H1N1)pdm09 (pH1N1). Demographic and clinical data were abstracted from medical records, using standardized case report forms. RESULTS: From 3 April 2009 through 10 August 2010, 1950 pH1N1 cases hospitalized in ICUs were reported. Of 1859 (95%) with information available, 1676 (90%) received NAI treatment, and 183 (10%) did not. The median age was 37 years (range, 1 week-93 years), 1473 (79%) had ≥1 comorbidity, and 492 (26%) died. The median time from symptom onset to starting NAI treatment was 4 days (range, 0-52 days). NAI treatment was associated with survival: 107 of 183 untreated case patients (58%) survived, compared with 1260 of 1676 treated case patients (75%; P ≤ .0001). There was a trend toward improved survival for those treated earliest (P < .0001). Treatment initiated within 5 days after symptom onset was associated with improved survival compared to those never treated (P < .05). CONCLUSIONS: NAI treatment of critically ill pH1N1 patients improves survival. While earlier treatment conveyed the most benefit, patients who started treatment up to 5 days after symptom onset also were more likely to survive. Further research is needed about whether starting NAI treatment >5 days after symptom onset may also convey benefit.

Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009.

BACKGROUND: During the spring of 2009, a pandemic influenza A (H1N1) virus emerged and spread globally. We describe the clinical characteristics of patients who were hospitalized with 2009 H1N1 influenza in the United States from April 2009 to mid-June 2009. METHODS: Using medical charts, we collected data on 272 patients who were hospitalized for at least 24 hours for influenza-like illness and who tested positive for the 2009 H1N1 virus with the use of a real-time reverse-transcriptase-polymerase-chain-reaction assay. RESULTS: Of the 272 patients we studied, 25% were admitted to an intensive care unit and 7% died. Forty-five percent of the patients were children under the age of 18 years, and 5% were 65 years of age or older. Seventy-three percent of the patients had at least one underlying medical condition; these conditions included asthma; diabetes; heart, lung, and neurologic diseases; and pregnancy. Of the 249 patients who underwent chest radiography on admission, 100 (40%) had findings consistent with pneumonia. Of the 268 patients for whom data were available regarding the use of antiviral drugs, such therapy was initiated in 200 patients (75%) at a median of 3 days after the onset of illness. Data suggest that the use of antiviral drugs was beneficial in hospitalized patients, especially when such therapy was initiated early. CONCLUSIONS: During the evaluation period, 2009 H1N1 influenza caused severe illness requiring hospitalization, including pneumonia and death. Nearly three quarters of the patients had one or more underlying medical conditions. Few severe illnesses were reported among persons 65 years of age or older. Patients seemed to benefit from antiviral therapy.

Systematic review of drug-drug interactions between rifamycins and anticoagulant and antiplatelet agents and considerations for management.

Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the activity of various drug transporting and metabolizing enzymes, which can impact the concentrations and efficacy of substrates. Many anticoagulant and antiplatelet (AC/AP) agents are substrates of these enzymes and have narrow therapeutic indices, leading to risks of thrombosis or bleeding when coadministered with rifamycins. The objective of this systematic review was to evaluate the effects on AC/AP pharmacokinetics, laboratory markers, and clinical safety and efficacy of combined use with rifamycins. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidance was performed. The PubMed, Embase, and Web of Science databases were queried for English-language reports on combination use of rifamycins and AC/AP agents from database inception through August 2021. The 29 studies identified examined warfarin (n = 17), direct oral anticoagulants (DOACs) (n = 8), and antiplatelet agents (n = 4) combined with rifampin (n = 28) or rifabutin (n = 1). Eleven studies were case reports or small case series; 14 reported on pharmacokinetic or laboratory markers in healthy volunteers. Rifampin-warfarin combinations led to reductions in warfarin area under the curve (AUC) of 15%-74%, with variability by warfarin isomer and study. Warfarin dose increases of up to 3-5 times prerifampin doses were required to maintain coagulation parameters in the therapeutic range. DOAC AUCs were decreased by 20%-67%, with variability by individual agent and with rifampin versus rifabutin. The active metabolite of clopidogrel increased substantially with rifampin coadministration, whereas prasugrel was largely unaffected and ticagrelor saw decreases. Our review suggests most combinations of AC/AP agents and rifampin are problematic. Further studies are required to determine whether rifabutin or rifapentine could be safe alternatives for coadministration with AC/AP drugs.

HIV-infected hospitalized patients with 2009 pandemic influenza A (pH1N1)--United States, spring and summer 2009.

We describe the clinical findings of HIV-infected patients hospitalized with 2009 pandemic influenza A (pH1N1). Data were derived from 3 separate case series in the United States. Among 911 adults hospitalized with pH1N1 influenza, 31 (3.4%) were HIV infected compared with an HIV prevalence of 0.45% in the general US adult population. HIV-infected influenza patients experienced similar rates of intensive care unit admission (29% vs 34%) and death (13% vs 13%) compared with non-HIV-infected patients. Among HIV-infected patients with available data, 14 (50%) of 28 patients had a CD4 cell count <200 cells/µL, which was not associated with an increased risk of an intensive care unit admission or death. Overall, 25 (81%) HIV-infected patients received influenza antiviral therapy, but treatment was initiated within 48 h of illness onset in only 33% of cases. Clinicians should consider early empiric influenza antiviral treatment in HIV-infected patients presenting with suspected influenza.

A novel risk factor for a novel virus: obesity and 2009 pandemic influenza A (H1N1).

BACKGROUND: many critically ill patients with 2009 pandemic influenza A (H1N1) (2009 H1N1) infection were noted to be obese, but whether obesity, rather than its associated co-morbidities, is an independent risk factor for severe infection is unknown. METHODS: using public health surveillance data, we analyzed demographic and clinical characteristics of California residents hospitalized with 2009 H1N1 infection to assess whether obesity (body mass index [BMI] ≥ 30) and extreme obesity (BMI ≥ 40) were an independent risk factor for death among case patients ≥ 20 years old. RESULTS: during the period 20 April-11 August 2009, 534 adult case patients with 2009 H1N1 infection for whom BMI information was available were observed. Two hundred twenty-eight patients (43%) were ≥ 50 years of age, and 378 (72%) had influenza-related high-risk conditions recognized by the Advisory Committee on Immunization Practices as risk factors for severe influenza. Two hundred and seventy-four (51%) had BMI ≥ 30, which is 2.2 times the prevalence of obesity among California adults (23%) and 1.5 times the prevalence among the general population of the United States (33%). Of the 92 case patients who died (17%), 56 (61%) had BMI ≥ 30 and 28 (30%) had BMI ≥ 40. In multivariate analysis, BMI ≥ 40 (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.4-5.9) and BMI ≥ 45 (OR, 4.2; 95% CI, 1.9-9.4), age ≥ 50 years (OR, 2.1; 95% CI, 1.2-3.7), miscellaneous immunosuppressive conditions (OR, 3.9; 95% CI, 1.6-9.5), and asthma (OR, 0.5; 95% CI, 0.3-0.9) were associated with death. CONCLUSION: half of Californians ≥ 20 years of age hospitalized with 2009 H1N1 infection were obese. Extreme obesity was associated with increased odds of death. Obese adults with 2009 H1N1 infection should be treated promptly and considered in prioritization of vaccine and antiviral medications during shortages.

Epidemiology of 2009 pandemic influenza A (H1N1) deaths in the United States, April-July 2009.

During the spring of 2009, pandemic influenza A (H1N1) virus (pH1N1) was recognized and rapidly spread worldwide. To describe the geographic distribution and patient characteristics of pH1N1-associated deaths in the United States, the Centers for Disease Control and Prevention requested information from health departments on all laboratory-confirmed pH1N1 deaths reported from 17 April through 23 July 2009. Data were collected using medical charts, medical examiner reports, and death certificates. A total of 377 pH1N1-associated deaths were identified, for a mortality rate of .12 deaths per 100,000 population. Activity was geographically localized, with the highest mortality rates in Hawaii, New York, and Utah. Seventy-six percent of deaths occurred in persons aged 18-65 years, and 9% occurred in persons aged ≥ 65 years. Underlying medical conditions were reported for 78% of deaths: chronic lung disease among adults (39%) and neurologic disease among children (54%). Overall mortality associated with pH1N1 was low; however, the majority of deaths occurred in persons aged <65 years with underlying medical conditions.

Characteristics of patients with oseltamivir-resistant pandemic (H1N1) 2009, United States.

During April 2009-June 2010, thirty-seven (0.5%) of 6,740 pandemic (H1N1) 2009 viruses submitted to a US surveillance system were oseltamivir resistant. Most patients with oseltamivir-resistant infections were severely immunocompromised (76%) and had received oseltamivir before specimen collection (89%). No evidence was found for community circulation of resistant viruses; only 4 (unlinked) patients had no oseltamivir exposure.

2009 pandemic influenza A (H1N1) virus infection in postpartum women in California.

OBJECTIVE: The objective of the study was to characterize severe illness because of the 2009 pandemic influenza A (H1N1) infection in postpartum women. STUDY DESIGN: We reviewed case reports of infected hospitalized postpartum (≤ 6 months from delivery) women identified through statewide surveillance in California. From April 23 through August 11, 2009, all hospitalizations and/or deaths were reported. After August 11, reporting was limited to cases requiring intensive care or deaths. RESULTS: From April 23 to December 31, 2009, 15 cases were reported; 11 (73%) had symptom onset within 7 days postpartum. Of 10 hospitalized cases reported through August 11, 4 required intensive care, 3 required mechanical ventilation, and 2 died. Of 5 cases requiring intensive care reported after August 11, all required mechanical ventilation and 1 died. Overall, 6 (43%) received antivirals within 48 hours of symptom onset. CONCLUSION: The 2009 H1N1 can cause severe illness in postpartum women, especially in the first week following delivery.