Archive for August, 2018

Rectal Chlamydia trachomatis and Neisseria gonorrhoeae Infections Among Women Reporting Anal Intercourse

Obstetrics & Gynecology September 2018  V.132 N.3  P.692–697

Llata, Eloisa, MD, MPH; Braxton, Jim; Asbel, Lenore, MD; Chow, Joan, PhD; Jenkins, Lindsay; Murphy, Ryan, PhD; Pathela, Preeti, DrPh; Schumacher, Christina, PhD; Torrone, Elizabeth, PhD

OBJECTIVE:

To examine the prevalence and treatment of rectal Chlamydia trachomatis and Neisseria gonorrhoeae infections among women reporting receptive anal intercourse in a network of sexually transmitted disease or sexual health clinics and estimate the proportion of missed infections if women were tested at the genital site only.

METHODS:

We conducted a cross-sectional analysis of C trachomatis and N gonorrhoeae test results from female patients reporting receptive anal intercourse in the preceding 3 months during visits to 24 sexually transmitted disease clinics from 2015 to 2016. Primary outcomes of interest were 1) anatomic site-specific C trachomatis and N gonorrhoeae testing and positivity among women attending selected U.S. sexually transmitted disease clinics who reported receptive anal intercourse and 2) the proportion of rectal infections that would have remained undetected if only genital sites were tested.

RESULTS:

Overall, 7.4% (3,743/50,785) of women reported receptive anal intercourse during the 2 years. Of the 2,818 women tested at both the genital and rectal sites for C trachomatis, 292 women were positive (61 genital only, 60 rectal only, and 171 at both sites). Of the 2,829 women tested at both the genital and rectal sites for N gonorrhoeae, 128 women were positive (31 genital only, 23 rectal only, and 74 at both sites). Among women tested at both anatomic sites, the proportion of missed C trachomatis infections would have been 20.5% and for N gonorrhoeae infections, 18.0%.

CONCLUSION:

Genital testing alone misses approximately one fifth of C trachomatis and N gonorrhoeae infections in women reporting receptive anal intercourse in our study population. Missed rectal infections may result in ongoing transmission to other sexual partners and reinfection.

FULL TEXT

https://journals.lww.com/greenjournal/Fulltext/2018/09000/Rectal_Chlamydia_trachomatis_and_Neisseria.22.aspx

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August 31, 2018 at 3:52 pm

Safety and efficacy of CURB65-guided antibiotic therapy in community-acquired pneumonia

Journal of Antimicrobial Chemotherapy  Feb. 2011 V.66 N.2 P.416-423

James D. Chalmers1,*, Aran Singanayagam2, Ahsan R. Akram2, Gourab Choudhury2, Pallavi Mandal2 and Adam T. Hill2

 

1MRC Centre For Inflammation Research, Queens Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK

2Department of Respiratory Medicine, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, UK

Objectives

To determine whether the introduction of a community-acquired pneumonia (CAP) severity assessment tool to guide antibiotic selection could reduce broad-spectrum antibiotic prescribing without compromising patient safety.

Methods

A prospective before and after evaluation study. Empirical antibiotic prescribing was studied for 18 months from June 2006 to January 2008 (pre-intervention) and then for 18 months following the implementation of a CURB65-guided antibiotic therapy guideline in June 2008. The primary outcome was the use of broad-spectrum antibiotics (cephalosporin, amoxicillin plus clavulanic acid and macrolides) in patients with CAP. Safety outcomes were 30 day mortality, requirement for mechanical ventilation and/or vasopressor support (MV/VS), development of complicated pneumonia, time to clinical stability (TCS) and length of hospital stay.

Results

The introduction of CURB65-guided therapy resulted in an overall reduction in the prescription of cephalosporins (from 27.1% of patients receiving this agent in the overall pre-intervention cohort to 8.0% in the post-intervention cohort, P<0.0001) and macrolides (72.8% to 58.7%, P<0.0001), particularly among low-risk patients. There was a corresponding increase in the prescription of the narrower-spectrum agent amoxicillin (29.7% to 41.7%, P<0.0001) and an increase in the use of amoxicillin monotherapy (10.4% to 29.9%, P<0.0001). Co-amoxiclav use increased slightly as this agent replaced cephalosporins as first-line treatment for severe CAP. The guideline had no impact on 30 day mortality, MV/VS, complicated pneumonia, TCS or length of stay. Following the intervention, adherence to national guidelines increased from 25.4% of prescriptions to 61.9%, suggesting the potential for further improvements.

Conclusions

CURB65-guided antibiotic therapy was associated with a significant decrease in broad-spectrum antibiotic use. The intervention was safe with no impact on mortality, treatment failure or clinical response.

PDF

http://jac.oxfordjournals.org/content/66/2/416.full.pdf+html

 

August 31, 2018 at 8:14 am

Ending Use of Oral Poliovirus Vaccine — A Difficult Move in the Polio Endgame

N Engl J of Medicine August 30, 2018  V.379 P.801-803

Perspective

M.A. Pallansch

When the world embarked on a mission of global polio eradication with the adoption of a World Health Assembly resolution in 1988, there was only minimal consideration of what would happen after the eradication of wild poliovirus (WPV) had been certified.

Poliovirus eradication efforts have targeted three distinct serotypes, using two vaccines, each containing components against all three types — a live attenuated oral poliovirus vaccine (OPV) used in more than 100 mostly low- and middle-income countries worldwide and an inactivated poliovirus vaccine (IPV) used in most of the developed world…

FULL TEXT

https://www.nejm.org/doi/full/10.1056/NEJMp1808903?query=TOC

PDF

https://www.nejm.org/doi/pdf/10.1056/NEJMp1808903

 

N Engl J of Medicine August 30, 2018  V.379 P.834-845

Type 2 Poliovirus Detection after Global Withdrawal of Trivalent Oral Vaccine

I.M. Blake and Others

BACKGROUND

Mass campaigns with oral poliovirus vaccine (OPV) have brought the world close to the eradication of wild poliovirus. However, to complete eradication, OPV must itself be withdrawn to prevent outbreaks of vaccine-derived poliovirus (VDPV). Synchronized global withdrawal of OPV began with serotype 2 OPV (OPV2) in April 2016, which presented the first test of the feasibility of eradicating all polioviruses.

METHODS

We analyzed global surveillance data on the detection of serotype 2 Sabin vaccine (Sabin-2) poliovirus and serotype 2 vaccine–derived poliovirus (VDPV2, defined as vaccine strains that are at least 0.6% divergent from Sabin-2 poliovirus in the viral protein 1 genomic region) in stool samples from 495,035 children with acute flaccid paralysis in 118 countries and in 8528 sewage samples from four countries at high risk for transmission; the samples were collected from January 1, 2013, through July 11, 2018. We used Bayesian spatiotemporal smoothing and logistic regression to identify and map risk factors for persistent detection of Sabin-2 poliovirus and VDPV2.

RESULTS

The prevalence of Sabin-2 poliovirus in stool samples declined from 3.9% (95% confidence interval [CI], 3.5 to 4.3) at the time of OPV2 withdrawal to 0.2% (95% CI, 0.1 to 2.7) at 2 months after withdrawal, and the detection rate in sewage samples declined from 71.0% (95% CI, 61.0 to 80.0) to 13.0% (95% CI, 8.0 to 20.0) during the same period. However, 12 months after OPV2 withdrawal, Sabin-2 poliovirus continued to be detected in stool samples (<0.1%; 95% CI, <0.1 to 0.1) and sewage samples (8.0%; 95% CI, 5.0 to 13.0) because of the use of OPV2 in response to VDPV2 outbreaks. Nine outbreaks were reported after OPV2 withdrawal and were associated with low coverage of routine immunization (odds ratio, 1.64 [95% CI, 1.14 to 2.54] per 10% absolute decrease) and low levels of population immunity (odds ratio, 2.60 [95% CI, 1.35 to 5.59] per 10% absolute decrease) within affected countries.

CONCLUSIONS

High population immunity has facilitated the decline in the prevalence of Sabin-2 poliovirus after OPV2 withdrawal and restricted the circulation of VDPV2 to areas known to be at high risk for transmission. The prevention of VDPV2 outbreaks in these known areas before the accumulation of substantial cohorts of children susceptible to type 2 poliovirus remains a high priority. (Funded by the Bill and Melinda Gates Foundation and the World Health Organization.)

FULL TEXT

https://www.nejm.org/doi/full/10.1056/NEJMoa1716677?query=TOC

PDF

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1716677

August 30, 2018 at 8:41 am

Activity of Telavancin against Staphylococcus aureus Isolates, Including Those with Decreased Susceptibility to Ceftaroline, from Cystic Fibrosis Patients

Antimicrobial Agents and Chemotherapy September 2018 V.62 N.9

Melanie Roch, Maria Celeste Varela, Agustina Taglialegna, Warren E. Rose and Adriana E. Rosato

Methicillin-resistant Staphylococcus aureus (MRSA) acquisition in cystic fibrosis (CF) patients confers a clinical outcome worse than that in non-CF patients with an increased rate of declined lung function.

Telavancin, an approved lipoglycopeptide used to treat infections due to S. aureus, has a dual mode of action causing inhibition of peptidoglycan synthesis and membrane depolarization. MRSA infections in CF patients remain an important problem with no foreseeable decline in prevalence rates.

Although telavancin is currently in clinical use for the treatment of complicated skin infections and hospital-acquired pneumonia, the activity against S. aureus infections in CF patients has not been investigated.

In this work, we studied the activity of telavancin against CF patient-derived S. aureus strains collected from geographically diverse CF centers in the United States.

We found that the telavancin MIC90 was 0.06 μg/ml, 8-fold lower than the ceftaroline or daptomycin MIC90 and 25-fold lower than the linezolid and vancomycin MIC90.

We demonstrate that telavancin at serum free concentrations has rapid bactericidal activity, with a decrease of more than 3 log10 CFU/ml being achieved during the first 4 to 6 h of treatment, performing better in this assay than vancomycin and ceftaroline, including against S. aureus strains resistant to ceftaroline.

Telavancin resistance was infrequent (0.3%), although we found that it can occur in vitro in both CF- and non-CF patient-derived S. aureus strains by progressive passages with subinhibitory concentrations.

Genetic analysis of telavancin-resistant in vitro mutants showed gene polymorphisms in cell wall and virulence genes and increased survival in a Galleria mellonella infection model.

Thus, we conclude that telavancin represents a promising therapeutic option for infections in CF patients with potent in vitro activity and a low resistance development potential.

FULL TEXT

https://aac.asm.org/content/62/9/e00956-18?etoc=

PDF

https://aac.asm.org/content/aac/62/9/e00956-18.full.pdf

August 29, 2018 at 3:46 pm

Bioequivalence of a Fixed-Dose Combination Tablet of the Complete Two-Drug Regimen of Dolutegravir and Rilpivirine for Treatment of HIV-1 Infection

Antimicrobial Agents and Chemotherapy September 2018 V.62 N.9

Rashmi Mehta, Allen Wolstenholme, Kristin Di Lullo, Caifeng Fu, Shashidhar Joshi, Herta Crauwels, Naomi Givens, Simon Vanveggel, Brian Wynne and Kimberly Adkison

A complete 2-drug regimen of dolutegravir at 50 mg and rilpivirine at 25 mg was approved to treat HIV-1 infection in virologically suppressed patients after demonstrating acceptable efficacy and tolerability.

This study investigated the bioequivalence and pharmacokinetics of the fixed-dose combination tablet compared with those of separate tablets. Secondary endpoints were the tolerability and safety of the fixed-dose combination tablet.

In this open-label, randomized-sequence, 2-way crossover trial, single doses of the fixed-dose combination tablet (the test treatment) and the combination of separate tablets (the reference treatment) were administered to healthy adults after a moderate-fat meal, with a 21-day washout between treatments.

Pharmacokinetic samples were collected through 12 days after dosing. The primary endpoints were the area under the plasma concentration-time curve (AUC) and the maximum concentration of drug in plasma (Cmax). The study employed a prespecified sample size reestimation based on a blind midpoint review of Cmax variability to update the enrollment size to achieve statistical power.

Of 118 participants enrolled, 113 received both treatments and underwent pharmacokinetic assessment.

The 90% confidence intervals for the geometric least-squares mean ratios for the AUC from 0 h to infinity, the AUC from 0 h to the last quantifiable measurement, and Cmax (test treatment versus reference treatment) were within the bioequivalence range of 0.80 to 1.25 for both drugs, indicating bioequivalence.

In this study, a single dose of either treatment was well tolerated overall, with 4% (n = 5) and 3% (n = 3) of participants reporting adverse events considered related to the test and reference treatments, respectively.

The dolutegravir-rilpivirine fixed-dose combination tablet is bioequivalent to a combination of separate tablets, and no new safety signals emerged.

(This study has been registered at ClinicalTrials.gov under identifier NCT02741557.)

FULL TEXT

https://aac.asm.org/content/62/9/e00748-18?etoc=

PDF

https://aac.asm.org/content/aac/62/9/e00748-18.full.pdf

August 29, 2018 at 3:45 pm

Neisseria meningitidis Antimicrobial Resistance in Italy, 2006 to 2016

Antimicrobial Agents and Chemotherapy September 2018 V.62 N.9

Paola Vacca, Cecilia Fazio, Arianna Neri, Luigina Ambrosio, Annapina Palmieri and Paola Stefanelli

The aim of this study was to evaluate the antimicrobial susceptibilities of 866 Neisseria meningitidis invasive strains during 11 years of surveillance in Italy.

Two and six strains were resistant to ciprofloxacin and rifampin, respectively. Forty-five percent were penicillin intermediate, associated with hypervirulent serogroup C clonal complex 11.

All of the strains were susceptible to cephalosporins.

FULL TEXT

https://aac.asm.org/content/62/9/e00207-18?etoc=

PDF

https://aac.asm.org/content/aac/62/9/e00207-18.full.pdf

August 29, 2018 at 3:43 pm

Ten-Day Quadruple Therapy Comprising Low-Dose Rabeprazole, Bismuth, Amoxicillin, and Tetracycline Is an Effective and Safe First-Line Treatment for Helicobacter pylori Infection in a Population with High Antibiotic Resistance: a Prospective, Multicenter, Randomized, Parallel-Controlled Clinical Trial in China

Antimicrobial Agents and Chemotherapy September 2018 V.62 N.9

Yong Xie, Zhenhua Zhu, Jiangbin Wang, Lingxia Zhang, Zhenyu Zhang, Hong Lu, Zhirong Zeng, Shiyao Chen, Dongsheng Liu, Nonghua Lv

The objective of this study was to investigate the efficacy and safety of 10-day bismuth quadruple therapy with amoxicillin, tetracycline, or clarithromycin and different doses of rabeprazole for first-line treatment of Helicobacter pylori infection.

This multicenter, randomized, parallel-controlled clinical trial was conducted between March 2013 and August 2014.

A total of 431 H. pylori-infected patients with duodenal ulcers were enrolled and randomized into four treatment groups (1:1:1:1) for 10 days, as follows: (i) a group receiving a low dose of rabeprazole of 10 mg twice a day (b.i.d.) (LR dose) plus bismuth, amoxicillin, and clarithromycin (LR-BAC); (ii) a group receiving LR plus bismuth, amoxicillin, and tetracycline (LR-BAT); (iii) a group receiving a high dose of rabeprazole of 20 mg b.i.d. (HR dose) plus bismuth, amoxicillin, and clarithromycin (HR-BAC); and (iv) a group receiving HR-BAT. Antimicrobial susceptibility was assessed by the Etest method.

The primary outcome was H. pylori eradication at 4 weeks after the treatment. The per-protocol (PP) eradication rates in the LR-BAC, LR-BAT, HR-BAC, and HR-BAT groups were 94.1%, 91.9%, 94.8%, and 91.9%, respectively, while the intention-to-treat (ITT) eradication rates in those groups were 87.2%, 87.2%, 87.7%, and 86%, respectively.

There was no significant difference between the four groups in PP analysis (P = 0.799) and ITT analysis (P = 0.985). The efficacies of four-treatment therapy were not affected by antibiotic resistance.

The adverse events in the four treatment groups were similar; central nervous system (CNS) and gastrointestinal symptoms were the most common reported.

Bismuth-containing quadruple therapy with low-dose rabeprazole, amoxicillin, and tetracycline is a good option for first-line treatment of H. pylori infection in a population with high antibiotic resistance.

(This study is registered at Chinese Clinical Trials Registry [www.chictr.org.cn] under number ChiCTR1800014832.)

FULL TEXT

https://aac.asm.org/content/62/9/e00432-18?etoc=

PDF

https://aac.asm.org/content/aac/62/9/e00432-18.full.pdf

August 29, 2018 at 3:41 pm

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