Stewardship / Resistance Scan for Sep 11, 2018

News brief

Study: Antibiotics do not reduce hospitalization risk for cough

A study published in the British Journal of General Practice yesterday shows that prescribing antibiotics to children with coughs does not reduce the risk of subsequent hospitalization.

The study involved researchers from the Universities of Bristol, Southampton, Oxford, and Kings College London, and looked at data on adverse outcomes in 8,320 children (ages 3 months to 15 years) who presented to their general practitioner (GP) with acute cough and other respiratory infection symptoms.

Immediate antibiotics were prescribed to 2,313 (27.8%) and delayed antibiotics to 771 (9.3%). Only 65 children (0.8%) children were hospitalized, and 350 (4.2%) revisited their GP for worsening of symptoms. Of the 65 children hospitalized, 25 (38.5%) had been prescribed an antibiotic.

"Compared with no antibiotics, there was no clear evidence that antibiotics reduced hospitalisations," the authors wrote. The immediate antibiotic risk ratio (RR) was 0.83 (95% confidence interval [CI], 0.47 to 1.45); delayed RR was 0.70 (95% CI, 0.26 to 1.90; overall P = 0.44).

"These results provide reassurance that, when faced with a child and uncertain prognosis, delayed prescribing can be a safe and effective method to reduce the child's probability of reconsulting with deterioration and can act as part of safety-netting strategies for parents," the authors concluded.
Sep 10 Br J Gen Pract study

Clinical trial doesn't support piperacillin-tazobactam for resistant BSIs

The results of a randomized clinical trial published today in JAMA indicate that the combination therapy piperacillin-tazobactam should not be used as carbapenem-sparing therapy in patients with bloodstream infections caused by ceftriaxone-resistant Escherichia coli or Klebsiella pneumoniae.

The noninferiority trial, the results of which were reported in April at the European Congress of Clinical Microbiology and Infectious Disease, included hospitalized patients with ceftriaxone-resistant E coli or K pneumoniae from 26 sites in nine countries. Patients were randomly assigned 1:1 to receive either 4.5 grams of piperacillin-tazobactam—a beta lactam/beta lactamase inhibitor combination—every 6 hours, or 1 gram of meropenem every 8 hours. The primary outcome was all-cause mortality at 30 days after randomization, with a 5% noninferiority margin.

A total of 378 participants completed the trial and were assessed for the primary outcome. Of the 187 patients randomized to piperacillin-tazobactam, 23 (12.3%) met the primary outcome of mortality at 30 days, compared with 7 of 191 (3.7%) patients randomized to meropenem. Results were consistent in an analysis of the per-protocol population, with 30-day mortality in the piperacillin-tazobactam patients significantly higher than those treated with meropenem (10.6% vs. 3.8%). In addition, serious adverse events occurred in 5 of 188 patients (2.7%) treated with piperacillin-tazobactam, compared with 3 of 191 patients (1.6%) in the meropenem group.

"Among patients with E coli or K pneumoniae bloodstream infections and ceftriaxone resistance definitive treatment with piperacillin-tazobactam compared with meropenem did not result in noninferior 30-day mortality," the authors concluded. "These findings do not support the use of piperacillin-tazobactam in this setting."
Sep 11 JAMA abstract
Apr 24 CIDRAP News story "Combo antibiotic found inferior for MDR bloodstream infections"

Data show non-inferiority for combo antibiotic for serious pneumonia

Merck today announced that its antibiotic Zerbaxa (ceftolozane combined with tazobactam) was shown non-inferior to meropenem for adult patients who had either ventilated hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP), the company said in a news release.

This prospective, randomized, double-blind, multicenter phase 3 study assessed the safety and efficacy of Zerbaxa compared with meropenem in 726 adults with either ventilated HABP or VABP requiring intravenous antibiotic therapy. In the study, Zerbaxa was administered in an investigational 3-gram dose (compared with 1 gram of meropenem), and both drugs were given intravenously every 8 hours for 8 to 14 days, or for 14 days for Pseudomonas aeruginosa infection. Meropenem is an approved broad-spectrum injectable antibiotic widely used to treat serious infections.

Zerbaxa met the pre-specified primary end points, demonstrating non-inferiority to meropenem in day 28 all-cause mortality and in clinical cure rate. Zerbaxa is currently indicated in US adults for treating complicated urinary tract infections caused by certain gram-negative bacteria and for complicated intra-abdominal infections caused by certain gram-negative and gram-positive bacteria. Merck is based in Kenilworth, N.J.

Based on the study results, Merck plans to submit supplemental new drug applications to the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for this new indication.

"HABP and VABP are serious and life-threatening hospital related pulmonary infections, especially in patients with severe underlying medical conditions," said Roy Baynes, MD, PhD, senior vice president with Merck.
Sep 11 Merck news release

Study shows little connection between C diff in food animals, humans

After observing a rise in Clostridioides difficile (formerly Clostridium difficile) infections in the central part of the state, Minnesota investigators discovered a 0% prevalence of C difficile in retail metal samples in the area and a 9% rate in animal fecal samples, but the isolates did not match human isolates well, demonstrating that neither meat nor food animals are an important source of infection in that area, according to a study yesterday in the Journal of Food Protection.

C difficile infection (CDI) can cause a serious, typically healthcare-associated infection. But community-associated CDI (CA-CDI) now accounts for about 50% of CDI cases in central Minnesota, the study authors write.

They said that, from November 2011 to July 2013, they cultured retail meat products and fecal samples from food-producing and companion animals in central Minnesota forthe pathogen using standard methods. They recovered no C difficile from 342 retail meat samples but 51 (9.1%) from 559 fecal samples from food-producing animals.

They then compared the 51 livestock isolates with 30 archived local veterinary C difficile isolates and 208 human CA-CDI case isolates from central Minnesota from 2012 from the Minnesota Department of Health. "Overall," the researchers write, "the 81 animal source isolates and 208 human source isolates were highly diverse genetically." Only 5 human isolates were classified as animal source.

"These data do not support meat products or food-producing and companion animals as important sources of CA-CDI in the central Minnesota study region," the authors conclude.
Sep 10 J Food Prot abstract

News Scan for Sep 11, 2018

News brief

UK reports second monkeypox case in traveler from Nigeria

In an unusual development, the United Kingdom today reported a second monkeypox case just 3 days after announcing its first case, but so far the investigation doesn't show a link between the two patients, Public Health England (PHE) said today in a statement.

As with the earlier case, the patient likely contracted the virus in Nigeria, which last fall reported its largest ever monkeypox outbreak. Several African nations have reported an increase in monkeypox activity since 2016.

The new UK case involved a patient who presented at Blackpool Victoria Hospital and was transferred to Royal Liverpool University Hospital. The earlier patient was diagnosed last week in Cornwall and is being treated at Royal Free Hospital in London.

Nick Phin, PhD, the deputy director of the National Infection Service at PHE, said monkeypox is probably still circulating in Nigeria and could affect travelers returning from that part of the world. "However, it is very unusual to see 2 cases in such a relatively short space of time," he said, adding that health officials are tracking the patient's contacts.
Sep 11 PHE update
Sep 10 CIDRAP News story "UK reports its first case of monkeypox"

Eggs linked to Salmonella infections in 2 states

The US Centers for Disease Control and Prevention (CDC) yesterday warned consumers not to eat, sell, or serve Gravel Ridge cage-free large eggs because of potential contamination with Salmonella Enteritidis, following reports of 14 people infected in Alabama and Tennessee.

The producer, Gravel Ridge Farms of Cullman, Ala., recalled the eggs on Sep 8 after receiving reports of illnesses. According to the recall notice, the US Food and Drug Administration (FDA) notified the company of the illnesses on Sep 6. The products were distributed between Jun 25 and Sep 6, mainly to restaurants and retail stores in Alabama, Georgia, and Tennessee.

According to the CDC, illness start dates range from Jul 10 to Aug 7. Of 14 infected people, 2 were hospitalized. No deaths were reported.
Sep 10 CDC food safety alert
Sep 10 CDC media statement
Sep 8 FDA recall notice

Study puts annual US fungal disease burden at over $7 billion

Researchers who studied medical costs of fungal diseases estimate that in 2017 they cost more than $7.2 billion, which includes $4.5 billion from hospitalizations and $2.6 billion from clinic visits. A team from the CDC published its findings yesterday in Clinical Infectious Diseases.

The investigators based their analysis on earlier insurance claims data, plus hospital discharge and outpatient data from two different sources. They adjusted the costs to 2017 dollars.

Of the 75,055 hospitalizations totaling $4.5 billion, the highest costs were related to two fungal diseases: Candida infections, which accounted for $1.4 billion, and Aspergillus illnesses, which cost $1.2 billion.

Dematophyte infections were responsible for nearly 5 million outpatient visits, at a price tag of $802 million, and 3.6 million visits were due to noninvasive candidiasis, at a cost of $1.6 billion.

Though interventions such as empiric treatment to prevent fungal diseases in certain high-risk patients is generally cost effective, the authors said benefits depend on the patient and baseline fungal infection rates. "More research is needed to better define optimal prophylaxis strategies for certain patient populations," they noted, adding that judicious use of antifungal agents and stewardship programs are warranted, given the threat of antifungal resistance, especially regarding Aspergillus and Candida.

Other prevention approaches include infection control steps and screening case-patient contacts for colonization, which they said is especially important for preventing Candida auris infections, an emerging multidrug-resistant organism.

Knowing the cost of fungal diseases helps better define the disease burden, they wrote, emphasizing that the ultimate goal is improving recognition, prevention, diagnosis, and treatment.
Sep 10 Clin Infect Dis abstract

Two doses of cholera vaccine offer 4 years of protection in Haitian study

An extended case-control study in Haiti showed that single-dose vaccination with a killed, bivalent, whole-cell oral cholera vaccine provided short-term protection, but vaccination with two doses provided protection against cholera for up to 4 years. The study was published in the September issue of The Lancet Global Health.

The study was conducted in Haiti from October of 2012 through November of 2016 and included 178 cases matched with 706 controls. Both cases and controls came from Haiti's Artibonite department, the epicenter of the country's cholera activity.

In adjusted analyses, the average cumulative 4-year effectiveness for two doses was 76% (95% CI, 59%-86%). Single-dose effectiveness decreased over time in a log-linear fashion, with a predicted vaccine effectiveness of 79% at the end of 12 months (95% CI, 43%-93%), which declined to zero before the end of the second year.

Cholera was introduced to Haiti in 2010, and since then the country has battled one of the worse outbreaks of the disease ever seen. This is the first study outside of Asia to measure the effectiveness of a two-dose vaccine.

Though single-dose protection offers benefit doing a short-term outbreak response, it is not an effective long-term control measure, the authors concluded.
September Lancet Glob Health study