Outcomes of Resistance-guided Sequential Treatment of Mycoplasma genitalium Infections: A Prospective Evaluation.

Background: Rising macrolide and quinolone resistance in Mycoplasma genitalium necessitate new treatment approaches. We evaluated outcomes of sequential antimicrobial therapy for M. genitalium guided by a macrolide-resistance assay. Methods: In mid-2016, Melbourne Sexual Health Centre switched from azithromycin to doxycycline (100 mg twice daily for 7 days) for nongonococcal urethritis, cervicitis, and proctitis. Cases were tested for M. genitalium and macrolide-resistance mutations (MRMs) by polymerase chain reaction. Directly after doxycycline, MRM-negative infections received 2.5 g azithromycin (1 g, then 500 mg daily for 3 days), and MRM-positive infections received sitafloxacin (100 mg twice daily for 7 days). Assessment of test of cure and reinfection risk occurred 14-90 days after the second antibiotic. Results: Of 244 evaluable M. genitalium infections (52 women, 68 heterosexual men, 124 men who have sex with men) diagnosed from 20 June 2016 to 15 May 2017, MRMs were detected in 167 (68.4% [95% confidence interval {CI}, 62.2%-74.2%]). Treatment with doxycycline decreased bacterial load by a mean 2.60 log10 (n = 56; P < .0001). Microbiologic cure occurred in 73 of 77 MRM-negative infections (94.8% [95% CI, 87.2%-98.6%]) and in 154 of 167 MRM-positive infections (92.2% [95% CI, 87.1%-95.8%]). Selection of macrolide resistance occurred in only 2 of 76 (2.6% [95% CI, .3%-9.2%]) macrolide-susceptible infections. Conclusions: In the context of high levels of antimicrobial resistance, switching from azithromycin to doxycycline for presumptive treatment of M. genitalium, followed by resistance-guided therapy, cured ≥92% of infections, with infrequent selection of macrolide resistance.

Symptoms, Sites, and Significance of Mycoplasma genitalium in Men Who Have Sex with Men.

During 2016-2017, we tested asymptomatic men who have sex with men (MSM) in Melbourne, Australia, for Mycoplasma genitalium and macrolide resistance mutations in urine and anorectal swab specimens by using PCR. We compared M. genitalium detection rates for those asymptomatic men to those for MSM with proctitis and nongonococcal urethritis (NGU) over the same period. Of 1,001 asymptomatic MSM, 95 had M. genitalium; 84.2% were macrolide resistant, and 17% were co-infected with Neisseria gonorrhoeae or Chlamydia trachomatis. Rectal positivity for M. genitalium was 7.0% and urine positivity was 2.7%. M. genitalium was not more commonly detected in the rectums of MSM (n = 355, 5.6%) with symptoms of proctitis over the same period but was more commonly detected in MSM (n = 1,019, 8.1%) with NGU. M. genitalium is common and predominantly macrolide-resistant in asymptomatic MSM. M. genitalium is not associated with proctitis in this population.

Use of Pristinamycin for Macrolide-Resistant Mycoplasma genitalium Infection.

High levels of macrolide resistance and increasing fluoroquinolone resistance are found in Mycoplasma genitalium in many countries. We evaluated pristinamycin for macrolide-resistant M. genitalium in a sexual health center in Australia. Microbiologic cure was determined by M. genitalium-specific 16S PCR 14-90 days after treatment began. Of 114 persons treated with pristinamycin, infection was cured in 85 (75%). This percentage did not change when pristinamycin was given at daily doses of 2 g or 4 g or at 3 g combined with 200 mg doxycycline. In infections with higher pretreatment bacterial load, treatment was twice as likely to fail for each 1 log10 increase in bacterial load. Gastrointestinal side effects occurred in 7% of patients. Pristinamycin at maximum oral dose, or combined with doxycycline, cured 75% of macrolide-resistant M. genitalium infections. Pristinamycin is well-tolerated and remains an option where fluoroquinolones have failed or cannot be used.

Detection of Chlamydia trachomatis mRNA using digital PCR as a more accurate marker of viable organism.

Spontaneous resolution of urogenital Chlamydia trachomatis (CT) without treatment has previously been described, but a limitation of these reports is that DNA or RNA-based amplification tests used do not differentiate between viable infection and non-viable DNA. We modified a previously published CT mRNA detection (omp2) method to differentiate between viable infection and non-viable DNA in a sample of CT DNA PCR positive women. We modified a CT mRNA detection (omp2) method from reverse transcriptase qPCR (RTqPCR) to digital PCR (dPCR) and evaluated it in samples from CT DNA positive women. Firstly, CT infected McCoy B cells treated with azithromycin in vitro identified detectable mRNA levels disappeared <2 days, while DNA persisted up to 6 days. We used 55 self-collected vaginal swabs from a cohort of women diagnosed as DNA positive for chlamydia obtained pre- and 7 days of post-azithromycin treatment. Concordance with DNA results was higher for dPCR than RTqPCR (74.5% versus 65.5%). At visit 1, there was a strong linear relationship between DNA and mRNA (r = 0.9, p < 0.000); 24 samples had both mRNA and DNA detected (82.8%) and 5 had only DNA detected with a potential false positive proportion of 17.2% (95%CI: 5.8, 35.8). At visit 2, there was poor correlation between DNA and mRNA (r = 0.14, p = 0.55); eight specimens had only DNA detected (42.1%; 95%CI: 20.25, 66.50) and one had mRNA detected. DNA detection methods alone may detect non-viable DNA. Consideration should be given to further develop mRNA assays as ancillary tests to improve detection of viable chlamydia.

Surveillance for Silicosis - Michigan and New Jersey, 2003-2011.

CDC's National Institute for Occupational Safety and Health (NIOSH), state health departments, and other state entities maintain a state-based surveillance program of confirmed silicosis cases. Data on confirmed cases are collected and compiled by state entities and submitted to CDC. This report summarizes information for cases of silicosis that were reported to CDC for 2003-2011 by Michigan and New Jersey, the only states that continue to provide data voluntarily to NIOSH. The data for this report were final as of January 8, 2015. Data are presented in tabular form on the number and distribution of cases of silicosis by year (Table 1), duration of employment in occupations with potential exposure to dust containing respirable crystalline silica (Table 2), industry (Table 3), and occupation (Table 4). The number of cases by year is presented graphically (Figure). This report is a part of the Summary of Notifiable Noninfectious Conditions and Disease Outbreaks - United States, which encompasses various surveillance years but is being published in 2016 (1). The Summary of Notifiable Noninfectious Conditions and Disease Outbreaks appears in the same volume of MMWR as the annual Summary of Notifiable Infectious Diseases (2).

Notes from the field: silicosis in a countertop fabricator - Texas, 2014.

In May 2014, the Texas Department of State Health Services was notified of a case of silicosis with progressive massive fibrosis in a Hispanic male aged 37 years who worked for an engineered stone countertop company as a polisher, laminator, and fabricator. He was exposed to dust for 10 years from working with conglomerate or quartz surfacing materials containing 70%-90% crystalline silica. This is the first reported case of silicosis associated with exposure to quartz surfacing materials in North America.

A cohort study of Chlamydia trachomatis treatment failure in women: a study protocol.

BACKGROUND: Chlamydia trachomatis is the most commonly diagnosed bacterial sexually transmitted infection in the developed world and diagnosis rates have increased dramatically over the last decade. Repeat infections of chlamydia are very common and may represent re-infection from an untreated partner or treatment failure. The aim of this cohort study is to estimate the proportion of women infected with chlamydia who experience treatment failure after treatment with 1 gram azithromycin. METHODS/DESIGN: This cohort study will follow women diagnosed with chlamydia for up to 56 days post treatment. Women will provide weekly genital specimens for further assay. The primary outcome is the proportion of women who are classified as having treatment failure 28, 42 or 56 days after recruitment. Comprehensive sexual behavior data collection and the detection of Y chromosome DNA and high discriminatory chlamydial genotyping will be used to differentiate between chlamydia re-infection and treatment failure. Azithromycin levels in high-vaginal specimens will be measured using a validated liquid chromatography-tandem mass spectrometry method to assess whether poor azithromycin absorption could be a cause of treatment failure. Chlamydia culture and minimal inhibitory concentrations will be performed to further characterize the chlamydia infections. DISCUSSION: Distinguishing between treatment failure and re-infection is important in order to refine treatment recommendations and focus infection control mechanisms. If a large proportion of repeat chlamydia infections are due to antibiotic treatment failure, then international recommendations on chlamydia treatment may need to be re-evaluated. If most are re-infections, then strategies to expedite partner treatment are necessary.

Emergency department security programs, community crime, and employee assaults.

BACKGROUND: Violence against health care workers is a serious occupational health hazard, especially for emergency department (ED) employees. A significant degree of variability in security programs among hospital EDs is present in part due to the absence of federal legislation requiring baseline security features. Nationally, only voluntary guidelines from the Occupational Safety and Health Administration (OSHA) for the protection of health care workers exist. OBJECTIVES: The purpose of this study was to examine ED security programs and employee assault rates among EDs with different financial resources, size, and background community crime rates. METHODS: This cross-sectional survey was conducted among large and small hospitals located in communities with low or high rates of community crime. Hospital financial data were collected through the state health department, and employee assault data were abstracted from hospital OSHA logs. Comparisons were made using a chi-squared or Wilcoxon test. RESULTS: Small hospitals located in towns with low community crime rates implemented the fewest security program features despite having the second highest rate of assault-related OSHA-recordable injuries among ED employees (0.66 per 100,000 staff hours). CONCLUSION: Due to the highly stressful workplace characteristics of EDs, the risk of employee assault is universal among all hospital sizes in all types of communities.

Strategies to Help CWS-Involved Parents Complete Substance Use Treatment and Protect their Children in Hawai'i.

Each year in Hawai'i, an estimated 500 - 650 children (about half of confirmed cases of child abuse or neglect) are at high risk of entering foster care because of their parent's substance use disorder (SUD). Children in foster care because of parental SUD are less likely to be reunified with their parents. Experiences in foster care may cause long-term negative health consequences for the children. Early identification and engagement of parents in SUD treatment can improve outcomes for parents and children. The child welfare and SUD treatment systems in Hawai'i are not set up to work together to maximize the likelihood that parents will complete treatment and families will stay together. This article recommends evidence-based interventions including recovery coaches, peer partners, and Family Drug Courts (FDCs). Recovery coaches and peer partners support parents in early engagement and completion of SUD treatment. FDCs provide an interdisciplinary approach that successfully serves parents involved with Child Welfare Services (CWS) who have complex needs. Effectively implementing these interventions in Hawai'i requires an improved infrastructure to collect and analyze data about parents with SUD and their children, parents' SUD needs and status in treatment, and families' level of CWS involvement. Data about the availability and delivery of services for CWS-involved parents with SUD are also needed to understand service efficiency and effectiveness. These suggested interventions would help more parents in Hawai'i complete treatment and keep their children safely with them, thereby protecting children's current and long-term health.

Repeat infections with chlamydia in women may be more transcriptionally active with lower responses from some immune genes.

Chlamydia trachomatis, the most common bacterial sexually transmitted infection worldwide, is responsible for considerable health burden due to its significant sequelae. There are growing concerns about chlamydial treatment and management due to widely documented increasing burden of repeat infections. In the current study, a cohort study design of 305 women with urogenital chlamydial infections demonstrated that 11.8% of women experienced repeat infections after treatment with azithromycin. The chlamydial DNA load measured by quantitative PCR was higher in women who experienced a repeat infection (p = 0.0097) and repeat infection was associated with sexual contact. There was no genomic or phenotypic evidence of azithromycin resistance within the chlamydial isolates. During repeat infection, or repeat positive tests during follow up, vaginal chlamydial gene expression (ompA, euo, omcB, htrA, trpAB) was markedly higher compared to baseline, and two of the selected immune genes analyzed had significantly lower expression at the time of repeat infection. Overall, there are two implications of these results. The results could be generalized to all recent infections, or repeat positive events, and indicate that chlamydial infections are have higher transcriptional activity of select genes early in the infection in women. Alternatively, after azithromycin treatment, repeat infections of Chlamydia may be more transcriptionally active at certain genes, and there may be post-treatment immunological alterations that interplay into repeat exposures establishing an active infection. The potential that recent infections may involve a higher level of activity from the organism may have implications for management by more regular testing of the most at risk women to reduce the risk of sequelae.

Measurement of tissue azithromycin levels in self-collected vaginal swabs post treatment using liquid chromatography and tandem mass spectrometry (LC-MS/MS).

BACKGROUND: Azithromycin is recommended for the treatment of uncomplicated urogenital chlamydia infection although the standard 1gram dose sometimes fails to eradicate the infection (treatment failure). One hypothesis proposed for treatment failure has been insufficient levels of the antibiotic at the site of infection. We developed an assay using liquid chromatography and tandem mass spectrometry (LC-MS/MS) to measure azithromycin concentration in high-vaginal swabs and monitor how concentration changes over time following routine azithromycin treatment. METHODS: Azithromycin concentrations were measured in two groups of women either within the first 24h of taking a 1g dose (N = 11) or over 9 days (N = 10). Azithromycin concentrations were normalised to an internal standard (leucine enkephalin), and the bulk lipid species phosphatidylcholine [PC(34:1)], using an Agilent 6490 triple quadrupole instrument in positive ionisation mode. The abundances of azithromycin, PC(34:1), and leu-enkephalin were determined by multiple reaction monitoring and absolute levels of azithromycin estimated using standard curves prepared on vaginal specimens. RESULTS: Vaginal azithromycin concentrations of women were rapidly obtained after 5h post-treatment (mean concentration = 1031mcg/mg of lipid, range = 173-2693mcg/mg). In women followed for 9 days, peak concentrations were highest after day 2 (mean concentration = 2206mcg/mg, range = 721-5791mcg/mg), and remained high for at least 9 days with a mean concentration of 384mcg/mg (range = 139-1024mcg/mg) on day 9. CONCLUSION: Our study confirmed that a single 1g dose of azithromycin is rapidly absorbed and remains in the vagina at relatively high levels for at least a week, suggesting that poor antibiotic absorption is unlikely to be an explanation for treatment failure.

High Cigarette and Poly-Tobacco Use Among Workers in a Dusty Industry: New Jersey Quarry Workers.

OBJECTIVE: Tobacco use is high among US extraction and construction workers, who can also incur occupational dust exposure. Information on different types of tobacco use among quarry/mine workers is sparse. METHODS: During mandated training sessions, New Jersey quarry workers were surveyed about their tobacco use. Prevalence was calculated for single and multiple tobacco use by demographic and workplace characteristics; logistic regression was used to assess associations with smoking. RESULTS: Two hundred forty (97.1%) workers completed surveys. Among respondents, 41.7% [95% confidence interval (95% CI) 35.4 to 48.3] currently used any tobacco product of whom 28.1% smoked cigarettes. In multivariate analysis, positive associations with smoking included working as a contractor versus mine employee (odds ratio 2.32, 95% CI 1.01 to 5.36) and a usual job title of maintenance (odds ratio 2.02, 95% CI 0.87 to 4.94). CONCLUSION: Industry-specific information may be helpful in developing targeted tobacco-cessation programs.