‘Antibiotic’ Tagged Posts

Antibiotic stewardship webinar recording Feb 2018



New single-dose antibiotic successfully treats uncomplicated gonorrhea infections


A section 2 medical trial led by Stephanie N. Taylor, MD, Professor of Medication and Microbiology within the Part of Infectious Illnesses at LSU Well being New Orleans College of Medication, has discovered new antibiotic successfully treats uncomplicated urogenital and rectal gonorrhea infections in a single oral dose. Outcomes are printed within the November eight, 2018, subject of the New England Journal of Medication.

“Based on the Facilities for Illness Management and Prevention, the incidence of gonorrhea within the US elevated by 67% from 2013 to 2017,” notes Dr. Taylor. “The micro organism inflicting gonorrhea, Neisseria gonorrhoeae, has developed resistance to each class of antibiotic at present advisable for remedy, and studies of multidrug-resistant N. gonorrhoeae necessitate the pressing improvement of recent antimicrobial brokers.”

The researchers carried out a randomized, open-label section 2 medical trial to find out the security and effectiveness of the investigational drug, zoliflodacin, in treating uncomplicated gonorrhea infections. Zoliflodacin, which has been fast-tracked by the FDA, works in a different way from the antibiotics at present accessible to deal with gonorrhea. It inhibits DNA biosynthesis in a brand new approach, impeding bacterial development. Entasis Therapeutics in Waltham, MA developed zoliflodacin.With a purpose of 144 individuals with gonorrhea, a complete of 179 individuals had been enrolled at sexual well being clinics in New Orleans, Seattle, Indianapolis, Birmingham and Durham, North Carolina from November 2014 by way of December 2015. The boys and non-pregnant girls, 18 – 55 years previous, had been eligible if that they had indicators and signs of urogenital gonorrhea, untreated urogenital gonorrhea or sexual contact within the previous 14 days with an individual who had gonorrhea. Urethral, cervical, pharyngeal and rectal swabs had been taken at enrollment. Thirty-eight individuals had been excluded resulting from unfavourable cultures. Individuals had been randomly assigned to obtain a single, oral dose of both 2 or Three grams of zoliflodacin or a single injected dose of 500 mg of ceftriaxone, one of many two medication at present used to deal with gonorrhea.

The microbiologic intention-to-treat (micro-ITT) group (141 individuals) included all individuals with gonorrhea at urethral or cervical websites. The per-protocol group included the individuals within the micro-ITT group who met all inclusion standards, didn’t have one other an infection apart from chlamydia or bacterial vaginosis, didn’t obtain every other systemic antibiotic earlier than check of treatment and returned for a test-of-cure go to inside a six-day window.

The first measure of efficacy was the proportion of individuals with urogenital infections who had been cured. The secondary measure of effectiveness was the variety of individuals whose pharyngeal and rectal infections had been cured. The first security consequence measure was the proportion of individuals reporting hostile occasions.

Therapy with 2 or Three g of zoliflodacin resulted in a 96% treatment charge in these with urogenital infections within the micro-ITT group, whereas the treatment charge for these handled with ceftriaxone was 100%. Within the per-protocol group, 98% of the individuals who took the 2-gram dose of zoliflodacin and 100% of those that acquired the Three-gram dose, in addition to the entire individuals within the ceftriaxone group, had been cured. All of these with rectal infections who had been handled no matter dose or remedy had been cured. Pharyngeal infections had been cured in four of eight individuals (50%), 9 of 11 individuals (82%), and four of four individuals (100%) within the teams that acquired 2 g of zoliflodacin, Three g of zoliflodacin, and ceftriaxone, respectively.

A complete of 21 hostile occasions had been related to zoliflodacin, largely gastrointestinal. Within the ceftriaxone group, 23 hostile occasions had been reported.

“Ceftriaxone is considered one of two medication used as the present customary of care to deal with uncomplicated gonorrhea,” provides Taylor. “A cephalosporin, it’s the final class of antibiotics we have now to deal with gonorrhea. Whereas it has labored effectively, we’re beginning to see resistance to it, too. Since there isn’t any vaccine to stop gonorrhea, and the opportunity of untreatable gonorrhea is looming bigger, it’s crucial that we develop new medication to deal with it. Our promising early outcomes recommend that zoliflodacin might be considered one of them.”

Based on the CDC, gonorrhea is the second mostly reported notifiable illness in the US. In 2017, a complete of 555,608 instances of gonorrhea had been reported in the US. Louisiana ranks second within the nation with 257 instances per 100,000 individuals reported final yr. Infections resulting from Neisseria gonorrhoeae are a serious reason behind pelvic inflammatory illness (PID) in the US. PID can result in severe outcomes in girls, similar to tubal infertility, ectopic being pregnant, and power pelvic ache. As well as, epidemiologic and biologic research present proof that gonococcal infections facilitate the transmission of HIV an infection.



Oral antibiotic reveals promise to remedy uncomplicated gonorrhea


An investigational oral antibiotic known as zoliflodacin was well-tolerated and efficiently cured most instances of uncomplicated gonorrhea when examined in a Part 2 multicenter medical trial, based on findings printed in the present day within the New England Journal of Medication. The Nationwide Institute of Allergy and Infectious Ailments (NIAID), a part of the U.S. Nationwide Institutes of Well being, sponsored the medical examine.

Gonorrhea is a standard sexually transmitted illness (STD) that impacts each women and men, significantly younger folks ages 15 to 24 years. Gonorrhea is the second mostly reported notifiable illness in america. In 2017, greater than 550,000 instances of gonorrhea had been reported in america. If untreated, gonorrhea an infection can result in pelvic inflammatory illness, ectopic being pregnant, infertility, and an elevated threat of HIV an infection. Pregnant ladies can cross the an infection to their infants, who can grow to be blind or develop life-threatening infections consequently.

Gonorrhea is brought on by the bacterium Nesseria gonorrhoeae, which has progressively developed resistance to every of the antimicrobials used to deal with it. In consequence, in 2015, the U.S. Facilities for Illness Management and Prevention revised gonorrhea remedy tips to advocate twin remedy with injectable ceftriaxone and oral azithromycin to cut back the emergence of resistance to ceftriaxone.

Zoliflodacin (previously generally known as ETX0914 and AZD0914), developed by Entasis Therapeutics based mostly in Waltham, Mass., represents a brand new sort of oral antibiotic that inhibits DNA synthesis another way than at present authorized antibiotics.

“The speed of reported gonorrhea instances in america has elevated 75 % because the historic low in 2009, and antibiotic resistance has significantly lowered the variety of remedy choices for this illness,” stated NIAID Director Anthony S. Fauci, M.D. “These encouraging analysis findings printed in the present day counsel that zoliflodacin has the potential to be a helpful and easy-to-administer oral antibiotic for treating gonorrhea.”

The examine occurred from November 2014 via December 2015 and was led by Stephanie N. Taylor, M.D., of Louisiana State College Well being Sciences Middle in New Orleans. Research investigators recruited sufferers from sexual well being clinics there and in Seattle; Indianapolis, Indiana; Birmingham, Alabama; and Durham, N.C. The trial enrolled 179 members (167 males and12 non-pregnant ladies) ages 18 to 55 years with both signs of uncomplicated urogenital gonorrhea, untreated urogenital gonorrhea or sexual contact with somebody with gonorrhea inside 14 days earlier than enrollment. Individuals had been randomly chosen to obtain both a single 2 or Three-gram dose of oral zoliflodacin or a 500-milligram (mg) dose of injectable ceftriaxone. Among the many 117 per-protocol members who had been evaluated six days after remedy, 98 % (48 of 49 members) of those that acquired the 2-gram zoliflodacin dose, 100 % (47 of 47 members) of those that acquired the Three-gram dose, and all (21 of 21) of the members within the ceftriaxone group had been thought-about cured of their urogenital gonorrhea based mostly on tradition outcomes.

Zoliflodacin cured all rectal gonorrheal infections (four of four members who acquired the 2-gram dose and 6 of 6 members who acquired the Three-gram dose) as did ceftriaxone (Three of three members). Nevertheless, the investigational drug didn’t fare as properly in treating sufferers with gonorrhea infections of the throat (pharyngeal): 67 % of volunteers who acquired the 2- gram dose (four of 6 members) and 78 % of those that acquired the Three-gram dose (7 of 9 members) had been cured. The entire members (four of four) within the ceftriaxone group achieved a remedy.

The investigational antibiotic was properly tolerated with transient gastrointestinal upset essentially the most generally reported adversarial impact. Microbiological analysis of post-treatment medical isolates didn’t display resistance to zoliflodacin.

In March 2018, NIAID accomplished a examine to judge zoliflodacin’s pharmacokinetics, security and tolerability as a single oral dose to function a bridge from the Part 2 medical trial formulation to the ultimate formulation for Part Three testing. Outcomes from that examine haven’t but been made public. Moreover, in September 2018 NIAID launched a Part 1 examine to judge the investigational drug’s cardiac results, an ordinary security check for brand new medication comparable to this.

Zoliflodacin has been awarded quick monitor standing by the U.S. Meals and Drug Administration for improvement as oral remedy for gonococcal infections. It’s anticipated to start Part Three testing within the Netherlands, South Africa, Thailand and america subsequent 12 months.



Antibiotic Stewardship Might Support Stepdown Therapies in CAP


October 04, 2018

This article originally appeared on Infectious Disease Advisor.
There were no differences in outcomes compared with patients receiving fluoroquinolone therapy.

There were no differences in outcomes compared with patients receiving fluoroquinolone therapy.

This article is part of MPR‘s coverage of IDWeek 2018, taking place in San Francisco, CA. Our on-site staff will be reporting on the latest breaking research and clinical advances in infectious diseases. Check back regularly for highlights from IDWeek 2018.

SAN FRANSISCO — The use of fluoroquinolones in stable patients with community-acquired pneumonia (CAP) can be reduced with the use of stewardship programs that share antibiotic use data and provide guidance for step-down therapy, according to new findings from a retrospective cohort study presented at ID Week 2018, held October 3-7 in San Francisco, California.

CAP guidelines recommend transitioning to an oral beta-lactam or fluoroquinolone regimen when patients are clinically stable, but because of common adverse effects, stewardship efforts are frequently focused on reducing initial fluoroquinolone use for CAP therapy. In this study the researchers hypothesized that the use of fluoroquinolones continues to be prevalent in treating CAP despite initial intravenous beta-lactam therapy, and examined factors associated with switching to oral beta-lactam vs a fluoroquinolone in 555 patients with CAP whose illness did not require admission to the intensive care unit.

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Data was collected during a 2-year period from 46 hospitals, and patients were included in the analysis if they received treatment with intravenous beta-lactam (ceftriaxone or ampicillin-sulbactam) plus macrolide/doxycycline by day 2 and then were switched to an oral fluoroquinolone or beta-lactam by day 4. More than half of the patients (54.4%) were switched to an oral beta-lactam vs 45.6% to a fluroquinolone by day 4.  Multivariable analysis showed that cardiovascular disease and higher CURB-65 Pneumonia Severity Calculator scores were more common in the oral beta-lactam cohort, but diabetes was less common. Lower fluoroquinolone use was associated with antibiotic selection data sharing among providers (83.1% vs 70.8%; odd ratio, .51; 95% CI, .27-.97; P =.04), but there were no differences in patient outcomes between the 2 groups.

“Although there were sicker patients in the oral beta-lactam group, there were no differences in outcomes between cohorts,” concluded the researchers.


Petty L, Patel TS, Conlon A, et al. Step-down therapy with oral fluoroquinolones vs oral beta-lactams for hospitalized adult patients with community-acquired pneumonia: a multi hospital cohort study. Presented at: IDWeek 2018; October 3-7, 2018; San Francisco, California. Abstract 216.

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One-month antibiotic routine to forestall TB as protected, efficient as nine-month remedy for HIV sufferers


A one-month antibiotic routine to forestall energetic tuberculosis (TB) illness was not less than as protected and efficient as the usual nine-month remedy for individuals residing with HIV, based on the outcomes of a giant worldwide scientific trial. Adults and adolescents within the trial had been extra prone to full the short-course regimen–consisting of each day doses of the antibiotics rifapentine and isoniazid for 4 weeks–than the usual nine-month routine of each day isoniazid.

The Section three scientific trial, referred to as ACTG 5279, was sponsored by the Nationwide Institute of Allergy and Infectious Ailments (NIAID), a part of the Nationwide Institutes of Well being, and carried out by the NIAID-funded AIDS Scientific Trials Group (ACTG). Richard E. Chaisson, M.D., professor of medication, epidemiology and worldwide well being at Johns Hopkins College and co-chair of the trial, introduced the findings March 5 on the 2018 Convention on Retroviruses and Opportunistic Infections (CROI) in Boston.

“Globally, tuberculosis kills extra individuals than another infectious illness, and it’s the main explanation for demise for individuals residing with HIV,” stated NIAID Director Anthony S. Fauci, M.D. “These outcomes have the potential to dramatically change scientific observe by providing individuals residing with HIV who’re vulnerable to creating energetic tuberculosis an extra, shorter-duration prevention possibility that’s protected, efficient and extra handy. This research additionally will inform future analysis on prevention of tuberculosis illness amongst HIV-negative individuals in danger for creating energetic tuberculosis.”

Worldwide, TB is the most typical severe opportunistic an infection in individuals residing with HIV. In 2016, TB accounted for 40 % of deaths amongst individuals residing with HIV, based on the World Well being Group (WHO). An estimated one-quarter of the world’s inhabitants has latent TB an infection. An individual with latent TB has been contaminated with tuberculosis-causing micro organism however doesn’t have any signs of the illness. Amongst individuals with latent TB an infection, HIV an infection is the best threat issue for development to energetic TB illness. Pores and skin or blood exams can detect latent TB an infection, however is probably not available in resource-limited areas. WHO pointers advocate TB prophylaxis for adults and adolescents residing with HIV who’ve both had a optimistic take a look at for latent TB or have an unknown TB standing and who would not have energetic TB.

Prophylactic antibiotic remedy to cease energetic TB from creating is efficient, however present preventive regimens are prolonged, could be tough for individuals to finish, and carry the chance of unwanted effects akin to liver harm. A six- to nine-month course of each day isoniazid has been the usual in lots of TB-endemic international locations, though WHO suggestions embrace completely different choices ranging as much as 36 months in size for individuals residing with HIV. Prior preclinical research had instructed that an ultra-short course of remedy could also be as efficient as an extended routine. Researchers suspected that it additionally might improve remedy adherence.

Between 2012 and 2014, the ACTG 5279 research enrolled three,000 individuals 13 years of age and older residing with HIV in Botswana, Brazil, Haiti, Kenya, Malawi, Peru, South Africa, Thailand, america and Zimbabwe. All members both lived in an space with a excessive TB burden or had had a pores and skin or blood take a look at indicating latent TB an infection. After they entered the research, roughly half of members had been taking antiretroviral remedy to deal with their HIV. On the time of research enrollment, choices on when to start out antiretroviral remedy usually had been primarily based on an individual’s CD4+ cell count–a measure of immune system well being. Present WHO pointers advocate that each one individuals residing with HIV start antiretroviral remedy as quickly as attainable after prognosis, no matter CD4+ cell rely.

Examine members had been randomly assigned to a one-month course of rifapentine and isoniazid or a nine-month course of isoniazid. Investigators monitored the members for a median of three years.

Total, TB incidence was decrease than anticipated and was comparable in each remedy arms, with 32 members assigned to the one-month routine and 33 to the nine-month routine creating energetic TB illness. No matter remedy kind, TB charges had been larger amongst members who weren’t on antiretroviral remedy initially of the research and amongst those that had had a optimistic TB pores and skin or blood take a look at. For members with low CD4+ cell counts–indicating an immune system weakened by HIV infection–at the beginning of the research, extra instances of energetic TB occurred amongst these receiving the short-course remedy in comparison with the usual routine. Nonetheless, this distinction was not statistically vital, that means it might need been as a result of likelihood.

Each preventive regimens had been protected, with fewer adversarial occasions occurring within the one-month remedy arm. Doable unwanted effects of each rifapentine and isoniazid embrace nausea, vomiting, liver issues and pores and skin rashes. Isoniazid can also trigger numbness and tingling within the extremities. Folks residing with HIV could also be notably susceptible to experiencing these unwanted effects.

Therapy adherence was considerably higher for the shorter routine. Practically all (97 %) of these assigned to the short-course remedy accomplished the complete antibiotic course, in comparison with 90 % of members within the nine-month arm.

“In contrast with customary tuberculosis preventive remedy for individuals residing with HIV, this short-course remedy is equally protected and efficient however reduces remedy time from 9 months to 1,” stated Dr. Chaisson. “This ultra-short course remedy may grow to be an essential software to regulate HIV-related tuberculosis and has the potential to rework international tuberculosis management efforts.”