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Background/Aims Although increased mortality has been reported among people with Mycobacterium avium complex pulmonary disease (MAC-PD), data are limited on survival associated with various antibiotic regimens used to treat MAC-PD. We conducted a comparative analysis of 3-year mortality in Medicare beneficiaries with bronchiectasis using various MAC-PD regimens. Methods We included Medicare beneficiaries aged ≥65 years with bronchiectasis (01/2006–12/2014). We limited our cohort to new MAC-PD therapy users. MAC-PD therapy was defined as ≥60-day prescriptions for a macrolide plus ≥1 other MAC-PD antibiotic. Guideline-based therapy (GBT) included a macrolide, ethambutol, and/or rifamycin. Using Cox proportional hazard models, we calculated adjusted hazard ratios (aHR) for death up to 3 years after therapy start between the following groups: (1) 2007 GBT versus non-GBT; (2) 2020 GBT versus non-GBT; and (3) macrolide-ethambutol-rifamycin (3-drug) versus macrolide-ethambutol (2-drug). Results We identified 4820 new MAC-PD therapy users, of whom 866 (17.9%) were deceased within 3 years of therapy initiation. Of 3040 (63.1%) beneficiaries prescribed 2007 GBT, 472 (15.5%) were deceased by 3 years, compared to 394 (22.1%) of 1780 (36.9%) prescribed non-GBT (aHR 0.82; 95% confidence interval [CI],.72–.94). We observed a similar trend for 2020 GBT versus non-GBT (aHR 0.81; 95% CI,.70–.94]). Three-year-mortality was similar between those starting 3-drug versus 2-drug regimens (aHR 0.89; 95% CI,.74–1.08]). Conclusions Among Medicare new MAC-PD therapy users, 3-year-mortality was higher in those prescribed non-GBT regimens compared to GBT regimens. Whether this finding suggests improved efficacy of GBT and/or differential characteristic of those using non-GBT regimens deserves further study. [ABSTRACT FROM AUTHOR]

Background Nontuberculous mycobacteria (NTM) cause pulmonary (PNTM) and extrapulmonary (ENTM) disease. Infections are difficult to diagnose and treat, and exposures occur in healthcare and community settings. In the United States, NTM epidemiology has been described largely through analyses of microbiology data from health departments, electronic health records, and administrative data. We describe findings from a multisite pilot of active, laboratory- and population-based NTM surveillance. Methods The Centers for Disease Control and Prevention's Emerging Infections Program conducted NTM surveillance at 4 sites (Colorado, 5 counties; Minnesota, 2 counties; New York, 2 counties; and Oregon, 3 counties [PNTM] and statewide [ENTM]) from 1 October 2019 through 31 March 2020. PNTM cases were defined using published microbiologic criteria. ENTM cases required NTM isolation from a nonpulmonary specimen, excluding stool and rectal swabs. Patient data were collected via medical record review. Results Overall, 299 NTM cases were reported (PNTM: 231, 77%); Mycobacterium avium complex was the most common species group. Annualized prevalence was 7.5/100 000 population (PNTM: 6.1/100 000; ENTM: 1.4/100 000). Most patients had signs or symptoms in the 14 days before positive specimen collection (ENTM: 62, 91.2%; PNTM: 201, 87.0%). Of PNTM cases, 145 (62.8%) were female and 168 (72.7%) had underlying chronic lung disease. Among ENTM cases, 29 (42.6%) were female, 21 (30.9%) did not have documented underlying conditions, and 26 (38.2%) had infection at the site of a medical device or procedure. Conclusions Active, population-based NTM surveillance will provide data for monitoring the burden of disease and characterize affected populations to inform interventions. [ABSTRACT FROM AUTHOR]

Background Mycobacterium abscessus is a virulent human pathogen. Treatment is complex and often poorly tolerated with suboptimal rates of eradication, highlighting the need for improved therapeutics. This study reports clinical experience with omadacycline for treatment of M abscessus infections at five large nontuberculous mycobacterial (NTM) disease clinics across the United States to better understand long-term safety and tolerability. Methods We conducted a multicenter retrospective chart review of adults with M abscessus infections. All patients treated with omadacycline as part of a multidrug therapeutic regimen through December 2021 were included. Clinical data from time of omadacycline initiation and up to 12 months of follow-up were collected. Descriptive statistics were performed. Results Analysis included 117 patients. Among patients with M abscessus isolate subspeciation, 58 of 71 (81.7%) were M abscessus spp abscessus. In isolates with reported drug susceptibility testing, 15 of 70 (21.4%) had confirmed susceptibility to macrolides. The most common site of infection was lungs. Median duration omadacycline treatment was 8 months (range, 0.25–33 months; interquartile range, 4–15 months). Omadacycline was discontinued in 60 patients (51.3%); 20 completed planned treatment course, 23 experienced intolerance or adverse event leading to drug cessation, and 17 stopped due to cost, death (unrelated to NTM infection or therapy), or another reason. In those with pulmonary disease, 44 of 95 (46%) had 1 or more negative cultures at time of final microbiological assessment, with 17 of 95 (18%) achieving culture conversion. Conclusions This study reports data supporting long-term safety and tolerability of omadacycline along with signal of effectiveness in treatment of M abscessus infections. [ABSTRACT FROM AUTHOR]

Background Nontuberculous mycobacteria are environmental organisms that cause infections leading to chronic, debilitating pulmonary disease, among which Mycobacterium avium complex (MAC) is the most common species. Methods We described patterns of macrolide-based multidrug antibiotic therapies for MAC pulmonary disease (MAC-PD) in US Medicare beneficiaries with bronchiectasis between January 2006 and December 2014. MAC therapy was defined as a multidrug regimen containing a macrolide plus ≥1 other drug targeting MAC-PD (rifamycin, ethambutol, fluoroquinolone, or amikacin) prescribed concomitantly for >28 days. Results We identified 9189 new MAC therapy users, with a mean age (standard deviation) of 74 (6 years) at the start of therapy; 75% female and 87% non-Hispanic white. A guideline-based regimen (a macrolide, ethambutol, and rifamycin, with or without amikacin) was prescribed for 51% of new MAC therapy users at treatment start, of whom 41% were continuing guideline-based therapy at 6 months, and only 18% at 12 months. Of all new MAC therapy users, by 18 months only 11% were still receiving MAC treatment, 55% had discontinued therapy, and 34% were censored owing to death or the end of the study period. Conclusions Overall, nearly half of new MAC therapy users were prescribed a non–guideline-recommended macrolide-based therapy, including regimens commonly associated with promoting macrolide resistance. Treatment discontinuation was common, and once discontinued, only a few beneficiaries resumed therapy at a later time. Our study adds important data to the current literature on treatment patterns for MAC-PD among older US populations. Future research should examine treatment patterns using more contemporary data sources. [ABSTRACT FROM AUTHOR]

Among 1038 participants with pulmonary Mycobacterium avium complex and 120 with Mycobacterium abscessus enrolled in the US Bronchiectasis and NTM Research Registry, less than half received antibiotic therapy in the 24 months before registry enrollment, of which less than half were guideline based. Adverse effects occurred in 21% of therapy recipients, of whom 33% discontinued therapy. [ABSTRACT FROM AUTHOR]

Background Opaganib, an oral sphingosine kinase-2 inhibitor with antiviral and anti-inflammatory properties, was shown to inhibit severe acute respiratory syndrome coronavirus 2 replication in vitro. We thus considered that opaganib could be beneficial for moderate to severe coronavirus disease 2019 (COVID-19) pneumonia. The objective of the study was to evaluate the safety of opaganib and its effect on supplemental oxygen requirements and time to hospital discharge in COVID-19 pneumonia hospitalized patients requiring supplemental oxygen. Methods This Phase 2a, randomized, double-blind, placebo-controlled study was conducted between July and December 2020 in 8 sites in the United States. Forty-two enrolled patients received opaganib (n = 23) or placebo (n = 19) added to standard of care for up to 14 days and were followed up for 28 days after their last dose of opaganib/placebo. Results There were no safety concerns arising in this study. The incidence of ≥Grade 3 treatment-emergent adverse events was 17.4% and 33.3% in the opaganib and placebo groups, respectively. Three deaths occurred in each group. A numerical advantage for opaganib over placebo was observed in in this nonpowered study reflected by total supplemental oxygen requirement from baseline to Day 14, the requirement for supplemental oxygen for at least 24 hours by Day 14, and hospital discharge. Conclusions In this proof-of-concept study, hypoxic, hospitalized patients receiving oral opaganib had a similar safety profile to placebo-treated patients, with preliminary evidence of benefit for opaganib as measured by supplementary oxygen requirement and earlier hospital discharge. These findings support further evaluation of opaganib in this population. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and an important cause of disease. The most common species causing pulmonary disease are members of Mycobacterium avium complex (MAC). MAC pulmonary disease (MAC-PD) can be chronic, debilitating, costly, and associated with a high mortality. However, MAC diagnoses are often delayed due to the nonspecific presentation of MAC-PD and radiological findings that overlap with other pulmonary diseases. Patients with risk factors and who meet the diagnostic criteria-which include clinical, radiological, and microbiologic criteria-should be considered for treatment. Diagnosis requires 2 or more positive sputum cultures or 1 bronchoscopic specimen culture. The recommendation for those who are treated is a 3-drug regimen including macrolide, rifamycin, and ethambutol that is continued for 12 months beyond sputum culture conversion to negative. MAC-PD is difficult to treat, with frequent drug-related side effects and suboptimal treatment outcomes. Refractory and recurrent disease is common, leading to lifelong follow-up of patients. There are limited treatment options for patients with macrolide-resistant or refractory disease. Amikacin liposome inhalation suspension is recommended for treatment-refractory patients whose cultures remain positive after 6 months of guideline-based therapy. Among the research priorities to improve patient outcomes and quality of life are developing new, more rapid diagnostic tests, investigating biomarkers associated with disease progression, and identifying new drugs and routes of administration as well as new, shorter, and better-tolerated regimens. [ABSTRACT FROM AUTHOR]

Objectives: Baricitinib is a selective oral inhibitor of JAK1/JAK2 for patients with moderately-to-severely active rheumatoid arthritis (RA). Baricitinib's safety profile in Japanese patients was evaluated using six studies (five Ph2/Ph3 trials, one long-term extension study through 01 September 2016) from an integrated database (nine RA studies). Methods: Incidence rates (IRs) or exposure-adjusted IRs (EAIRs) of adverse events (AEs) per 100 patient-years (PY) were calculated using data which included RA patients exposed to any baricitinib dose. Results: Five hundred and fourteen Japanese patients received baricitinib for 851.5 total PY of exposure (median 1.7 years, maximum 3.2). The EAIR of treatment-emergent AEs was 57.4/100PY. There were no deaths; 31 patients had serious infections (IR: 3.6/100PY), 55 herpes zoster (6.5), 0 tuberculosis, 10 malignancies (1.1) including two lymphomas, two major cardiovascular AEs (0.3), one gastro- intestinal perforation (0.1), and four deep vein thrombosis (0.5). In Japanese patients, herpes zoster was more frequent than that of patients overall in the integrated database, but the events were considered manageable. Conclusion: In this analysis, baricitinib had acceptable safety profile in Japanese RA patients in the context of demonstrated efficacy. Aside from herpes zoster, baricitinib safety was not notably different between Japanese RA patients and those RA patients in the integrated database. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the risk of serious infection (SI) and herpes zoster (HZ) in rheumatoid arthritis patients receiving JAK inhibitors. Methods We conducted a systematic literature review and meta-analysis of phase II and III randomized controlled trials of tofacitinib (5 mg bid), baricitinib (4 mg od) and upadacitinib (15 mg od). Patient-exposure years were calculated. A per-protocol analysis was applied, incorporating follow-up time from patients randomized to placebo who cross into the treatment arm. Pooled incidence rates per 100 person-years of SI and HZ were calculated. Incidence rate ratios (IRRs) of drug vs placebo were compared using a meta-synthesis approach. Results Twenty-one studies were included in the meta-analysis; 11 tofacitinib (5888 patients), six baricitinib (3520 patients) and four upadacitinib studies (1736 patients). For SI, the incidence rates were 1.97 (95% CI: 1.41, 2.68), 3.16 (95% CI: 2.07, 4.63) and 3.02 (95% CI: 0.98, 7.04), respectively. The IRRs comparing treatment arm to placebo were statistically non-significant: 1.22 (95% CI: 0.60, 2.45), 0.80 (95% CI: 0.46, 1.38) and 1.14 (95% CI: 0.24, 5.43), respectively. For HZ, the incidence rates were 2.51 (95% CI: 1.87, 3.30), 3.16 (95% CI: 2.07, 4.63) and 2.41 (95% CI: 0.66, 6.18), respectively. The IRR of HZ comparing baricitinib with placebo was 2.86 (95% CI: 1.26, 6.50). Non-significant IRRs were seen with tofacitinib and upadacitinib: 1.38 (95% CI: 0.66, 2.88) and 0.78 (95% CI: 0.19, 3.22), respectively. Indicator opportunistic infections excluding HZ were too rare to provide meaningful incidence rates. Conclusion The absolute SI rates were low. However across the JAK inhibitors, the incidence of HZ is higher than expected for the population (3.23 per 100 patient-years). While the risk was numerically greatest with baricitinib, indirect comparisons between the drugs did not demonstrate any significant difference in risk. Systematic review registration number Prospero 2017 CRD4201707879. [ABSTRACT FROM AUTHOR]

A cluster of 3 facial Mycobacterium chelonae infections occurred after cosmetic dermal filler injections at a plastic surgery clinic. Pulsed-field gel electrophoresis showed that M chelonae isolated from the clinic tap water were identical to the patient wound isolates. Review of injection procedures identified application of nonsterile ice to the skin prior to injection as a possible source of M chelonae. Surveys of regional laboratories and a national plastic surgery listserv identified no other cases related to the injection of this brand of dermal filler. This is the first report of cutaneous M chelonae infections following the injection of dermal fillers. It adds to a growing body of literature on postinjection M chelonae infections and reinforces the importance of optimal skin disinfection steps prior to percutaneous procedures.Level of Evidence: 5 [ABSTRACT FROM PUBLISHER]

Background. Nontuberculous mycobacteria (NTM) are important human pathogens, yet little is known about disease prevalence in the United States. Reports suggest prevalence has increased, particularly in women, but population-based data to substantiate this are lacking. We sought to estimate NTM disease prevalence in Oregon, and describe disease by site, species, and patient demographic characteristics. Methods. We contacted laboratories that performed mycobacterial cultures on Oregon residents in 2005-2006. For each isolate, we obtained source, collection date, species, and patient demographics. We used the microbiologic component of the American Thoracic Society/Infectious Diseases Society of America's pulmonary NTM disease criteria to define cases of pulmonary NTM, and patients with isolates from a normally sterile site were classified as having extrapulmonary disease. Results. We identified 933 patients with ≥1 NTM isolate. Of these, 527 (56%) met the case definition (annualized prevalence, 7.2 cases per 100,000 persons). Pulmonary cases predominated (5.6 cases per 100,000 persons), followed by skin/soft-tissue cases (0.9 cases per 100,000 persons). Mycobacterium avium complex was the most common species identified in pulmonary cases (4.7 cases per 100,000 persons). Pulmonary disease prevalence was significantly higher in women (6.4 cases per 100,000 persons) than men (4.7 cases per 100,000 persons) and was highest in persons aged >50 years (15.5 cases per 100,000 persons). Conclusions. NTM are frequently isolated from Oregon residents; more than one-half of all isolates likely represent true disease. Pulmonary NTM is most common among elderly women, and M. avium causes most disease. Future efforts to monitor disease trends should be undertaken, and efforts made to validate the use of the ATS/IDSA microbiologic criteria alone to predict pulmonary NTM disease. [ABSTRACT FROM AUTHOR]

Background. After World War II, residents of Satowan (population, 650 persons), an outer island in the state of Chuuk, Federated States of Micronesia, noted a high prevalence of a chronic, progressive skin disease known locally as "spam." Methods. Island residents who had chronic, progressive verrucous or keloidal plaques for 13 months were considered case patients. Tissue specimens were obtained for culture, histopathological analysis, mycobacterial polymerase chain reaction (PCR), and comparison with the hsp65 gene of Mycobacterium marinum. We performed a case-control study involving all cases and randomly selected control individuals from the community. Results. A total of 39 case patients were identified, with a median age of 26.0 years (range, 8-82 years); 74.4% were male, and the mean duration of disease was 12.5 years. A total of 98 control individuals were enrolled. Results of all 19 mycobacterial tissue cultures were negative, and histopathological analysis of all 9 lesions showed suppurative granulomatous inflammation with negative results of mycobacterial and fungal stains. In 7 of 9 paraffinembedded samples, nontuberculous mycobacterial DNA was detected by PCR, and 2 sequenced products had 95% and 87% identity to M. marinum. All case patients were taro farmers (odds ratio, undefined; P ! .01), and among taro farmers, when the analysis was controlled for sex, contact with water-filled World War II-era bomb craters was associated with infection (odds ratio, 8.2; P ! .01). Conclusions. "Spam disease" is a chronic, progressive skin disease of high prevalence on Satowan and is associated with taro farming and contact with World War II-era bomb craters. Histopathological and PCR data demonstrate a nontuberculous mycobacterial infection as the cause. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacterial infections are becoming more common. Recently, Mycobacterium fortuitum and other rapidly growing mycobacteria have been found to cause severe skin and soft-tissue infections in association with nail salon whirlpool footbaths. We recently investigated a large outbreak of M. fortuitum furunculosis among women who received pedicures at a single nail salon. To better define the clinical course of such infections, we collected clinical details from physicians who were treating outbreak patients. We constructed multivariable linear models to evaluate the effect of antibiotic treatment on disease duration. Sixty-one patients were included in the investigation. The mean disease duration was 170 days (range, 41- 336 days). Forty-eight persons received antibiotic therapy for a median period of 4 months (range, 1-6 months), and 13 persons were untreated. Isolates were most susceptible to ciprofloxacin and minocycline. Early ad- ministration of therapy was associated with shorter duration of disease only in persons with multiple boils (P < .01). One untreated, healthy patient had lymphatic disease dissemination. [ABSTRACT FROM AUTHOR]

We present the results of a nationwide survey of infectious disease consultants to identify mycobacterial and other serious infections in patients receiving anti-tumor necrosis factor compounds and other novel targeted therapies. Non-tuberculous mycobacterial infections, histoplasmosis, and invasive Staphylococcus aureus infection were all reported more frequently than was tuberculosis disease in this context. [ABSTRACT FROM AUTHOR]

Background Limited data are available regarding laboratory abnormalities in patients with pulmonary Mycobacterium avium complex (MAC) disease. Methods We included patients without cystic fibrosis who had pulmonary MAC and met ATS/IDSA disease criteria from the Northwest NTM Biobank with a complete blood count (CBC) 6 months prior and up to 30 days after study enrollment. The biobank is a cohort of patients with Nontuberculous mycobacterium (NTM) infections identified through statewide laboratory surveillance and OHSU regional referral NTM clinic; a complete clinical history is collected by chart review at enrollment. We evaluated the proportion of pulmonary MAC patients with abnormal laboratory tests. We examined differences using a chi-square test between patients who were antimycobacterial treatment naïve, on therapy at enrollment or previously treated, in addition to cavitary and non-cavitary disease and those who also had previous sputum isolation of additional organisms (co-isolation). Results 147 patients had CBCs available; 112 (76.2%) were female with a median age of 69 years (22–88 years). 64 (43.5%) were antimycobacterial treatment naïve, 65 (44.2%) were on therapy at enrollment and 18 (12.2%) were previously treated. Lymphocyte count was below normal in 105 (73.4%) patients; 70 (49.3%) had lymphocyte counts below 1500 cells/mL and 27 (18.9%) were lymphopenic. Elevated monocyte percent was seen in 54 (37.2%) patients. Lymphopenia was more common in those on therapy, P = 0.01. There were no predominant laboratory abnormalities in 108 patients with metabolic panels. 34 patients had a c-reactive protein (CRP) collected, which was elevated, after age and gender correction, in 31 patients (91.2%). There was no significant difference between treatment groups. Eleven patients had cavitary disease with no differences in laboratory values compared with those with non-cavitary disease. Patients with co-isolation were more likely to be anemic (P = 0.03), have thrombocytosis (P = 0.04) and were less likely to have a monocytosis (P = 0.03). Conclusion A large proportion of patients with pulmonary MAC disease have low lymphocyte counts, elevated monocyte percent and CRP. Further evaluation of the meaning of these abnormalities as well as changes during therapy is needed. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Immunosuppressive therapy for connective tissue diseases (CTDs) increases risk for opportunistic infections including Pneumocystis pneumonia (PCP). High mortality rates are reported in CTD patients with PCP, which suggests a potential need for prophylaxis, but indications remain poorly defined. Wide variations in the use of PCP prophylaxis among rheumatologists have been documented. This study evaluated PCP prophylaxis patterns for CTD patients among infectious disease (ID) physicians. Methods An electronic survey was emailed to 1264 adult ID physicians who are members of the Infectious Diseases Society of America Emerging Infections Network. Results Six hundred thirty-one physicians responded to the survey. Respondents to the survey were more likely to work in academics (P =.02) and be early (<5 years) or late (≥25 years) in their careers (P =.0002). Forty-three percent (n = 269) made no recommendations for PCP prophylaxis in non-HIV patients. Of the 362 respondents who did make such recommendations, the greatest consensus for disease-based prophylaxis was for granulomatosis with polyangiitis (53%). For therapy-based prophylaxis, corticosteroids ≥20 mg/d was the most frequently cited indication (87%). Surrogate laboratory markers to aid in decisions about prophylaxis were not routinely used (21%). Although the majority recommended discontinuation of PCP prophylaxis with tapering of corticosteroids (65%), there was variability in the specific dose. Eighty-nine percent of respondents felt that guidelines about PCP prophylaxis would be helpful. Conclusions There is little consensus about PCP prophylaxis in CTDs among ID physicians. Guidelines for PCP prophylaxis would be helpful when caring for these complex patients. [ABSTRACT FROM AUTHOR]

International travel for the purpose of receiving medical care is increasing. We report a case of disseminated mycobacterial infection after fetal stem cell infusion. [ABSTRACT FROM AUTHOR]

The article provides information on the diagnosis of the cutaneous infection due to Mycobacterium chelonae. It states that black ink of the tattoo is found to be associated with mycobacterial infection involving M. chelonae. It further states that prevention of the M. chelonae from the ink of the tattoo can be done by sterilizing the ink with saline.

Presents a letter to the editor focusing on tuberculosis cases associated with infliximab and etanercept.

A response by Kevin L. Winthrop, S. Yamashita, and S. Beekmann to a letter to the editor about the clinical differences between tuberculosis that occurs in patients who received with monoclonal antibodies that was published in the previous issue.