Treatment of latent TB is an important public-health strategy, but 9 months of daily isoniazid (270 doses) poses challenges for compliance. In this study, 3 months of weekly isoniazid plus ...rifapentine (12 doses) was found to be noninferior to 9 months of isoniazid alone.
Tuberculosis results in nearly 2 million deaths annually worldwide.
1
More than 2 billion persons are infected with
Mycobacterium tuberculosis,
2
and from this reservoir active tuberculosis will develop in millions of persons in coming decades. Treatment of latent
M. tuberculosis
infection among the persons at highest risk for progression to active disease is an important strategy for tuberculosis control and elimination.
3
–
6
The current standard regimen for the treatment of latent
M. tuberculosis
infection is 9 months of daily isoniazid.
3
The efficacy for isoniazid was found to be 69 to 93% in a study that was published in 1982 (before the . . .
In January 2020, Santa Clara County, California, USA, began identifying laboratory-confirmed coronavirus disease among residents. County staff conducted case and contact investigations focused on ...households and collected detailed case demographic, occupation, exposure, and outcome information. We describe the first 200 test-positive cases during January 31-March 20, 2020, to inform future case and contact investigations. Probable infection sources included community transmission (104 cases), known close contact with a confirmed case-patient (66 cases), and travel (30 cases). Disease patterns across race and ethnicity, occupational, and household factors suggested multiple infection risk factors. Disproportionately high percentages of case-patients from racial and ethnic subgroups worked outside the home (Hispanic 86% and Filipino 100%); household transmission was more common among persons from Vietnam (53%). Even with the few initial cases, detailed case and contact investigations of household contacts capturing occupational and disaggregated race and ethnicity data helped identify at-risk groups and focused solutions for disease control.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Centers for Disease Control and Prevention and National Institutes of Health convened a multidisciplinary meeting to discuss surrogate markers of treatment response in tuberculosis. The goals ...were to assess recent surrogate marker research and to provide specific recommendations for (1) the qualification and validation of biomarkers of treatment outcome; (2) the standardization of specimen and data collection for future clinical trials, including a minimum set of samples and collection time points; and (3) the creation ofa specimen repository to support biomarker testing. This article summarizes these recommendations and provides a roadmap for their implementation.
IMPORTANCE: Three months of a once-weekly combination of rifapentine and isoniazid for treatment of latent tuberculosis infection is safe and effective for persons 12 years or older. Published data ...for children are limited. OBJECTIVES: To compare treatment safety and assess noninferiority treatment effectiveness of combination therapy with rifapentine and isoniazid vs 9 months of isoniazid treatment for latent tuberculosis infection in children. DESIGN, SETTING, AND PARTICIPANTS: A pediatric cohort nested within a randomized, open-label clinical trial conducted from June 11, 2001, through December 17, 2010, with follow-up through September 5, 2013, in 29 study sites in the United States, Canada, Brazil, Hong Kong (China), and Spain. Participants were children (aged 2-17 years) who were eligible for treatment of latent tuberculosis infection. INTERVENTIONS: Twelve once-weekly doses of the combination drugs, given with supervision by a health care professional, for 3 months vs 270 daily doses of isoniazid, without supervision by a health care professional, for 9 months. MAIN OUTCOMES AND MEASURES: We compared rates of treatment discontinuation because of adverse events (AEs), toxicity grades 1 to 4, and deaths from any cause. The equivalence margin for the comparison of AE-related discontinuation rates was 5%. Tuberculosis disease diagnosed within 33 months of enrollment was the main end point for testing effectiveness. The noninferiority margin was 0.75%. RESULTS: Of 1058 children enrolled, 905 were eligible for evaluation of effectiveness. Of 471 in the combination-therapy group, 415 (88.1%) completed treatment vs 351 of 434 (80.9%) in the isoniazid-only group (P = .003). The 95% CI for the difference in rates of discontinuation attributed to an AE was −2.6 to 0.1, which was within the equivalence range. In the safety population, 3 of 539 participants (0.6%) who took the combination drugs had a grade 3 AE vs 1 of 493 (0.2%) who received isoniazid only. Neither arm had any hepatotoxicity, grade 4 AEs, or treatment-attributed death. None of the 471 in the combination-therapy group developed tuberculosis vs 3 of 434 (cumulative rate, 0.74%) in the isoniazid-only group, for a difference of −0.74% and an upper bound of the 95% CI of the difference of +0.32%, which met the noninferiority criterion. CONCLUSIONS AND RELEVANCE: Treatment with the combination of rifapentine and isoniazid was as effective as isoniazid-only treatment for the prevention of tuberculosis in children aged 2 to 17 years. The combination-therapy group had a higher treatment completion rate than did the isoniazid-only group and was safe. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00023452
OBJECTIVE:Compare the effectiveness, tolerability, and safety of 3 months of weekly rifapentine and isoniazid under direct observation (3HP) versus 9 months of daily isoniazid (9H) in HIV-infected ...persons.
DESIGN:Prospective, randomized, and open-label noninferiority trial.
SETTING:The United States , Brazil, Spain, Peru, Canada, and Hong Kong.
PARTICIPANTS:HIV-infected persons who were tuberculin skin test positive or close contacts of tuberculosis cases.
INTERVENTION:3HP versus 9H.
MAIN OUTCOME MEASURES:The effectiveness endpoint was tuberculosis; the noninferiority margin was 0.75%. The tolerability endpoint was treatment completion; the safety endpoint was drug discontinuation because of adverse drug reaction.
RESULTS:Median baseline CD4 cell counts were 495 (IQR 389–675) and 538 (IQR 418–729) cells/μl in the 3HP and 9H arms, respectively (P = 0.09). In the modified intention-to-treat analysis, there were two tuberculosis cases among 206 persons 517 person-years (p-y) of follow-up in the 3HP arm (0.39 per 100 p-y) and six tuberculosis cases among 193 persons (481 p-y of follow-up) in the 9H arm (1.25 per 100 p-y). Cumulative tuberculosis rates were 1.01 versus 3.50% in the 3HP and 9H arms, respectively (rate difference−2.49%; upper bound of the 95% confidence interval of the difference0.60%). Treatment completion was higher with 3HP (89%) than 9H (64%) (P < 0.001), and drug discontinuation because of an adverse drug reaction was similar (3 vs. 4%; P = 0.79) in 3HP and 9H, respectively.
CONCLUSION:Among HIV-infected persons with median CD4 cell count of approximately 500 cells/μl, 3HP was as effective and safe for treatment of latent Mycobacterium tuberculosis infection as 9H, and better tolerated.
3 months of weekly rifapentine plus isoniazid (3HP) and 4 months of daily rifampicin (4R) are recommended for tuberculosis preventive treatment. As these regimens have not been compared directly, we ...used individual patient data and network meta-analysis methods to compare completion, safety, and efficacy between 3HP and 4R.
We conducted a network meta-analysis of individual patient data by searching PubMed for randomised controlled trials (RCTs) published between Jan 1, 2000, and Mar 1, 2019. Eligible studies compared 3HP or 4R to 6 months or 9 months of isoniazid and reported treatment completion, adverse events, or incidence of tuberculosis disease. Deidentified individual patient data from eligible studies were provided by study investigators and outcomes were harmonised. Methods for network meta-analysis were used to generate indirect adjusted risk ratios (aRRs) and risk differences (aRDs) with their 95% CIs.
We included 17 572 participants from 14 countries in six trials. In the network meta-analysis, treatment completion was higher for people on 3HP than for those on 4R (aRR 1·06 95% CI 1·02-1·10; aRD 0·05 95% CI 0·02-0·07). For treatment-related adverse events leading to drug discontinuation, risks were higher for 3HP than for 4R for adverse events of any severity (aRR 2·86 2·12-4·21; aRD 0·03 0·02-0·05) and for grade 3-4 adverse events (aRR 3·46 2·09-6·17; aRD 0·02 0·01-0·03). Similar increased risks with 3HP were observed with other definitions of adverse events and were consistent across age groups. No difference in the incidence of tuberculosis disease between 3HP and 4R was found.
In the absence of RCTs, our individual patient data network meta-analysis indicates that 3HP provided an increase in treatment completion over 4R, but was associated with a higher risk of adverse events. Although findings should be confirmed, the trade-off between completion and safety must be considered when selecting a regimen for tuberculosis preventive treatment.
None.
For the French and Spanish translations of the abstract see Supplementary Materials section.
Outbreaks of postoperative surgical-site infections or bloodstream infections are usually thought to be related to the surgeon or the surgical procedure. In May and June 1990, the Centers for Disease ...Control (CDC) were notified of the simultaneous and sudden onset of postoperative infections of the bloodstream, surgical sites, or other sites involving a variety of organisms at hospitals in four states. These outbreaks were investigated and traced to the use of a newly introduced anesthetic agent, propofol (Diprivan, Stuart Pharmaceuticals, Wilmington, Del.).
1
Propofol is a sterile, white, nonpyrogenic, oil-based anesthetic agent that is given intravenously; approved by the Food and . . .
Background. Overall rates of noncompletion of treatment (NCT) for latent tuberculosis infection (LTBI) in the PREVENT TB trial were 18% for 3 months of directly observed once-weekly rifapentine ...(maximum dose, 900 mg) plus isoniazid (maximum dose, 900 mg) (3HP-DOT) and 31% for 9 months of daily self-administered isoniazid (maximum dose, 300 mg; 9H-SAT). NCT for LTBI reduces its effectiveness. The study objective was to assess factors associated with NCT for LTBI among adult participants enrolled at US and Canadian sites of the PREVENT TB trial. Methods. This was a post hoc exploratory analysis of the randomized, open-label PREVENT TB trial. Factors were analyzed by univariate and multivariate logistic regression (with enrollment site as a random effect). Results. From 6232 participants analyzed, 1406 (22.6%) did not complete LTBI treatment (317 NCT attributed to an adverse event NCT-AE and 1089 NCT attributed to reasons other than an adverse event NCT-O). The proportion of NCT-AE was similar with both regimens (3HP-DOT = 6.4% vs 9H-SAT = 5.9%; P = .23); NCT-O was higher among participants enrolled in 9H-SAT (9H-SAT = 24.5% vs 3HP-DOT = 12.7%; P = .02). Among those in the NCT-AE group, being non-Hispanic and receiving 3HP-DOT, having cirrhosis and receiving 9H-SAT, alcohol consumption among men, and use of concomitant medication were associated with NCT-AE. Among those in the NCT-O group, receiving 9H-SAT, missing ≥1 early visit, men receiving 9H-SAT, men with a history of incarceration, alcohol abuse, use ever of intravenous drugs, younger age receiving 9H-SAT, and smoking were associated with NCT-O. Conclusions. Factors associated with NCT, such as missing a clinic visit early during treatment, might help identify persons for whom tailored interventions could improve completion of LTBI treatment. Clinical Trials Registration. NCT00023452.
Background:
Stenotrophomonas maltophilia
is a gram-negative, biofilm-producing bacterium that is ubiquitous in water environments and often associated with healthcare-associated infections (HAIs). ...Outbreaks of
S. maltophilia
bloodstream infections are a rare event and raise the suspicion of a common source. We used whole-genome sequencing (WGS) for an investigation of a cluster of
S. maltophilia
HAIs at a single hospital.
Methods:
A patient was defined as an intensive care unit (ICU) patient with fever and
S. maltophilia
isolated from a culture and who was treated for an HAI from May to October 2022. The response to the cluster included an epidemiologic investigation, water infection control risk assessments (WICRA), and environmental sampling. We also conducted WGS to characterize and assess relatedness between clinical and environmental
S. maltophilia
isolates.
Results:
From May 5 to October 1, 2022, we identified 11 HAIs due to
S. maltophilia
: 9 bloodstream infections and 2 ventilator-associated pneumonia cases. The initial epidemiological investigation did not identify common medical products, procedures, or personnel as an exposure source. The WICRA identified several breaches that may have exposed patients to contaminated water from sink backsplashes in the ICU, computerized tomography (CT) rooms, and the emergency department. In the CT rooms, saline bags were sometimes used for multiple patients, as were single-use intravenous contrast solution bottles. No additional cases were identified once infection control breaches were mitigated by installing sink splashguards, disinfecting drains, dedicating sink use for handwashing, and adhering to single-patient use of pharmaceutical products in the CT rooms. Of 46 environmental water samples, 19 were culture-positive for
S. maltophilia
. Isolates available for WGS included 7 clinical isolates (6 blood and 1 respiratory) and 17 environmental isolates. Among the 24 isolates sequenced, 16 unique multilocus sequence types (MLSTs) were identified. The 6 blood isolates sequenced were highly related (ST239, 0–4 high-quality, single-nucleotide variants hqSNV over 98.99% core genome), suggesting a common source. Two clusters of related environmental isolates were identified; however, overall MLST and hqSNV analyses suggested no relatedness between clinical and environmental isolates.
Conclusions:
An ICU cluster of
S. maltophilia
bloodstream infections was likely associated with water contamination of room surfaces and use of single-use intravenous products for multiple patients in the setting of a national pharmaceutical product shortage. This investigation highlights the importance of strong surveillance and water infection control, including routine assessment of ancillary areas in which intravenous products are administered and interdisciplinary collaboration to properly mitigate nosocomial transmission.
Disclosures:
None
Data on the detailed clinical progression of COVID-19 in conjunction with epidemiological and virological characteristics are limited. In this case series, we describe the first 12 US patients ...confirmed to have COVID-19 from 20 January to 5 February 2020, including 4 patients described previously
. Respiratory, stool, serum and urine specimens were submitted for SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) testing, viral culture and whole genome sequencing. Median age was 53 years (range: 21-68); 8 patients were male. Common symptoms at illness onset were cough (n = 8) and fever (n = 7). Patients had mild to moderately severe illness; seven were hospitalized and demonstrated clinical or laboratory signs of worsening during the second week of illness. No patients required mechanical ventilation and all recovered. All had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset. Lowest real-time PCR with reverse transcription cycle threshold values in the upper respiratory tract were often detected in the first week and SARS-CoV-2 was cultured from early respiratory specimens. These data provide insight into the natural history of SARS-CoV-2. Although infectiousness is unclear, highest viral RNA levels were identified in the first week of illness. Clinicians should anticipate that some patients may worsen in the second week of illness.
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