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


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.


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.


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%.


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.



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


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.


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.


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.


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.



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


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…




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


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.


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.


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.


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.)



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.



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 under identifier NCT02741557.)



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.



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 [] under number ChiCTR1800014832.)



August 29, 2018 at 3:41 pm

β-Lactam Dosage Regimens in Septic Patients with Augmented Renal Clearance

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

Alexandra Jacobs, Fabio Silvio Taccone, Jason A. Roberts, Frédérique Jacobs, Frederic Cotton, Fleur Wolff, Jacques Creteur, Jean-Louis Vincent and Maya Hites

Augmented renal clearance is commonly observed in septic patients and may result in insufficient β-lactam serum concentrations.

The aims of this study were to evaluate potential correlations between drug concentrations or total body clearance of β-lactam antibiotics and measured creatinine clearance and to quantify the need for drug dosage adjustments in septic patients with different levels of augmented renal clearance.

We reviewed 256 antibiotic measurements (512 drug concentrations) from a cohort of 215 critically ill patients who had a measured creatinine clearance of ≥120 ml/min and who received therapeutic drug monitoring of meropenem, cefepime, ceftazidime, or piperacillin from October 2009 until December 2014 at Erasme Hospital.

Population pharmacokinetic (PK) analysis of the data was performed using the Pmetrics software package for R. Fifty-five percent of drug concentrations showed insufficient β-lactam serum concentrations to treat infections due to Pseudomonas aeruginosa.

There were significant, yet weak, correlations between measured creatinine clearance and trough concentrations of meropenem (r = −0.21, P = 0.01), trough concentrations of piperacillin (r = −0.28, P = 0.0071), concentrations at 50% of the dosage interval (r = −0.41, P < 0.0001), and total body clearance of piperacillin (r = 0.39, P = 0.0002).

Measured creatinine clearance adequately explained changes in drug concentrations in population pharmacokinetic models for cefepime, ceftazidime, and meropenem but not for piperacillin.

Therefore, specific PK modeling can predict certain β-lactam concentrations based on renal function but not on absolute values of measured creatinine clearance, easily available for clinicians.

Currently, routine therapeutic drug monitoring is required to adjust daily regimens in critically ill patients receiving standard dosing regimens.



August 29, 2018 at 3:39 pm

Pharmacokinetics, Safety, and Tolerability of Single and Multiple Doses of Relebactam, a β-Lactamase Inhibitor, in Combination with Imipenem and Cilastatin in Healthy Participants

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

Elizabeth G. Rhee, Matthew L. Rizk, Nicole Calder, Marcela Nefliu, Steven J. Warrington, Michael S. Schwartz, Eric Mangin, Keith Boundy, Pratik Bhagunde, Francheska Colon-Gonzalez, Patricia Jumes, Yang Liu and Joan R. Butterton

Relebactam is a novel class A and C β-lactamase inhibitor that is being developed in combination with imipenem-cilastatin for the treatment of serious infections with Gram-negative bacteria.

Here we report on two phase 1 randomized, double-blind, placebo-controlled pharmacokinetics, safety, and tolerability studies of relebactam administered with or without imipenem-cilastatin to healthy participants: (i) a single-dose (25 to 1,150 mg) and multiple-dose (50 to 625 mg every 6 h [q6h] for 7 to 14 days) escalation study with men and (ii) a single-dose (125 mg) study with women and elderly individuals.

Following single- or multiple-dose intravenous administration over 30 min, plasma relebactam concentrations declined biexponentially, with a terminal half-life (t1/2) ranging from 1.35 to 1.85 h independently of the dose.

Exposures increased in a dose-proportional manner across the dose range. No clinically significant differences in pharmacokinetics between men and women, or between adult and elderly participants, were observed. Urine pharmacokinetics demonstrated that urinary excretion is the major route of relebactam elimination.

No drug-drug interaction between relebactam and imipenem-cilastatin was observed, and the observed t1/2 values for relebactam, imipenem, and cilastatin were comparable, thus supporting coadministration.

Relebactam administered alone or in combination with imipenem-cilastatin was well tolerated across the dose ranges studied. No serious adverse events or deaths were reported.

The pharmacokinetic profile and favorable safety results supported q6h dosing of relebactam with imipenem-cilastatin in clinical treatment trials.



August 29, 2018 at 3:38 pm

South African guideline for the management of community-acquired pneumonia in adults

Journal of Thoracic Disease June 2017 V.9 N.6 P.1469-1502.

South African Thoracic Society; Federation of Infectious Diseases Societies of Southern Africa.

Tom H. Boyles1, Adrian Brink1,2, Greg L. Calligaro3, Cheryl Cohen4,5, Keertan Dheda3, Gary Maartens6, Guy A. Richards7, Richard van Zyl Smit3, Clifford Smith8, Sean Wasserman1, Andrew C. Whitelaw9,10, Charles Feldman11; South African Thoracic Society, Federation of Infectious Diseases Societies of Southern Africa

Improving the care of patients with community-acquired pneumonia (CAP) in South Africa is particularly important because of the high burden of disease and the need to improve standards of antibiotic prescribing in the face of rising antimicrobial resistance (AMR). The purpose of this document is to provide clinicians guidance as to the recommended management of patients with CAP. This is an update for clinicians, which takes into account important advances and controversies in the management of patients with CAP.



August 29, 2018 at 11:23 am

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