ASP Scan (Weekly) for Jun 28, 2019

Dental overprescribing in Japan
;
Rapid tests and unneeded antibiotics
;
Procalcitonin meta-analysis
;
Overprescribing for pediatric UTIs
;
Fast-track for pneumonia antibiotic
;
Highly resistant gonorrhea in Taiwan
;
New pneumonia antibiotic
;
UK AMR funding
;
Core stewardship and antibiotic use
;
Antibiotic overuse in dengue

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

Dentist survey finds antimicrobial overprescribing may be common

A survey of Japanese dentists indicates that attitudes toward antimicrobial prophylaxis vary widely, with many reporting going against current guidelines, Japanese researchers reported today in a letter in Infection Control and Hospital Epidemiology.

The online questionnaire was sent to 231 dentists attending a regional dental conference, and 111 responded. Regarding the use of prophylactic antimicrobials against infective endocarditis, more than 80% of respondents said they understood the guidelines for prevention, yet more than 70% said they believe it's important to continue administering antimicrobials after a dental procedure, and more than 80% reported having prescribed prophylactic antimicrobials to patients with high-risk cardiac conditions both before and after a procedure, even though that contradicts the current guidelines.

In addition, the questionnaire results showed that antimicrobial prophylaxis for patients with non-high-risk cardiac condition was also common, even though that too goes against current guidelines. And more than half of the respondents reported prescribing antimicrobials only after an invasive dental procedure to prevent local infection and complications, even though guidelines recommend administering antimicrobial prophylaxis before a procedure.

The authors of the letter say the self-reported behavior reflects deeply entrenched misperceptions about the relevant pathophysiology and fears of litigation.

"Current practice patterns suggest that antimicrobials may be overprescribed in dentistry," they write. "Intervention is urgently needed to optimize antimicrobial prescription in dentistry."
Jun 28 Infect Control Hosp Epidemiol abstract

 

Study indicates potential need for stewardship of rapid diagnostics

In another study today in Infection Control and Hospital Epidemiology, researchers found that despite diagnosis of a viral respiratory infection with a rapid diagnostic test, more than 20% of patients discharged from three emergency departments (EDs) in a California health system were prescribed antibiotics.

The retrospective study found that, of 323 patients discharged from the emergency departments from October 2016 to March 2017 with a viral respiratory infection—diagnosed by a multiplex polymerase chain reaction (PCR) test—68 (21.1%) were prescribed antibiotics. Multivariate analysis identified several factors associated with patients who received antibiotics, including age (median, 59.3 vs 43 years; P = .04), longer duration of symptoms (median 4 vs 2 days; P = .002), receipt of antibiotics in the preceding 7 days (27.9% vs 9.8%; P < .001), and abnormal chest x-rays (64.5% vs 28.4%; P < .001). The authors say these factors suggest increased clinical concern for a secondary bacterial infection or medical fragility.

Patients were more likely to receive antibiotics for a diagnosis of pneumonia (39.7% vs 1.6%; P < .001) or otitis media (7.4% vs 0.4%; P = .002), and were less likely with a diagnosis of upper respiratory infection (2.9% vs 13.7%; P = .02) or influenza (20.6% vs 44.3%; P < .001).

The authors say the findings indicate the need for healthcare systems to implement more stringent stewardship of molecular diagnostics. They conclude, "Opportunities exist for antimicrobial stewardship strategies to incorporate rapid diagnostics in promoting judicious antibiotic usage in the ED."
Jun 28 Infect Control Hosp Epidemiol abstract

 

Meta-analysis finds little use for procalcitonin in guiding CAP treatment

Originally published by CIDRAP News Jun 26

A meta-analysis of 12 studies indicates that serum procalcitonin levels are unlikely to help clinicians determine whether community-acquired pneumonia (CAP) in adults requires antibiotics, researchers from Baylor College of Medicine reported yesterday in Clinical Infectious Diseases.

The US Food and Drug Administration (FDA) approved the use of procalcitonin—a peptide with serum levels that are believed to increase during bacterial infections—to help clinicians determine whether antibiotics are needed, and when they should be stopped, in patients with lower respiratory tract infections, including CAP. But the researchers note that many of the studies supporting the procalcitonin-guided protocol have been in pediatric patients in whom etiologies have been established, or adults with a variety of respiratory disorders. They wanted to evaluate the performance of procalcitonin in adult CAP patients in whom the etiology was established.

In their review of the 12 studies, which included 2,408 adult patients hospitalized with CAP, the researchers found that the sensitivity and specificity of serum procalcitonin (at a cutoff of 0.5 micrograms per liter) were 0.55 (95% confidence interval [CI], 0.37 to 0.71) and 0.76 (95% CI, 0.62 to 0.86), respectively. From these results, they determined that the sensitivity and specificity of procalcitonin are both too low and too variable to be used in distinguishing bacterial from viral pneumonia and determining whether antibiotics are needed.
Jun 25 Clin Infect Dis abstract

 

Greek data reveal high prescribing rate for kids' urinary tract infections

Originally published by CIDRAP News Jun 26

Greek researchers have identified high prescribing rates and prolonged intravenous antibiotic treatments in children treated for urinary tract infections (UTIs) at a Greek hospital, according to a study yesterday in the Journal of Global Antimicrobial Resistance.

Among 230 neonates, infants, and older children admitted to the hospital with a UTI over a 5-year period, 459 antibiotic prescriptions were identified, with amikacin (31.2%), amoxicillin-clavulanic acid (17.4%), and ampicillin (13.5%) the most commonly prescribed agents. Children received prolonged IV treatment for febrile and afebrile UTIs for a mean of 5.4 days and 4.7 days, respectively. Analysis of isolates found that the main causative organism was Escherichia coli (79.2%), and high resistance rates were reported for ampicillin (42%), trimethoprim-sulfamethoxazole (26.5%), and amoxicillin-clavulanic acid (12.2%). Lower resistance rates were identified for 3rd generation cephalosporins (1.7%), nitrofurantoin (2.3%), ciprofloxacin (1.3%), and amikacin (0.9%).

The authors of the study conclude that antimicrobial stewardship programs and regular monitoring for resistance could help minimize inappropriate prescribing for UTIs.
Jun 25 J Glob Antimicrob Resist abstract

 

FDA grants priority review for expanded indication for Baxdela

Originally published by CIDRAP News Jun 26

The FDA has granted priority review status to a supplemental New Drug Application (sNDA) for the fluorquinolone antibiotic Baxdela (delafloxacin), according a news release from drug maker Melinta Therapeutics.

The sNDA filing seeks to expand the indication for Baxdela, which was approved by the FDA in 2017 for use in patients with acute bacterial skin and skin structure infections, to include adult patients with community-acquired bacterial pneumonia (CABP). The application is based on the results of a phase 3 clinical trial that found that Baxdela had comparable efficacy to moxifloxacin for early clinical response and clinical outcome at test of cure in CABP patients, and was generally safe and well-tolerated. The drug has demonstrated effectiveness against gram-negative and gram-positive pathogens.

"Baxdela's potency and activity against the most common bacterial pathogens seen in CABP indicate it could play a significant role in the treatment of this life-threatening illness, if approved," Melinta Chief Medical Officer Sue Cammarata, MD, said in the news release. "We look forward to working with the FDA to help evaluate bringing this potential option to people with CABP as soon as possible."

The FDA is expected to make a ruling on the sNDA by Oct 24, 2019.
Jun 19 Melinta Therapeutics news release

 

High-level azithromycin-resistant gonorrhea increases in Taiwan

Originally published by CIDRAP News Jun 25

A study yesterday in Antimicrobial Agents and Chemotherapy details the emergence of gonorrhea strains with high-level resistance to azithromycin in Taiwan.

In an evaluation of 598 Neisseria gonorrhoeae isolates obtained from patients in Taiwan from 2001 to 2018, researchers found that 8.7% (52 of 598 isolates) were resistant to azithromycin and 1.7% (10/598) exhibited high-level resistance. All of the isolates with high-level azithromycin resistance had non-mosaic penA alleles and the same molecular resistance determinants, including four mutated 23S rRNA copies with A2059G mutation, -35A deletion in the promoter region of the mtrR gene, and G45D mutation in the mtrR coding region.

An analysis of the genetic relatedness of the 52 isolates found 24 different multilocus sequence typing (MLST) types, with ST1901, ST1583, ST7371, and ST11196 being the most prevalent among the azithromycin-resistant isolates. Among the 10 isolates with high-level azithromycin resistance, nine were identified as MLST12039 and one belonged to MLST10899. The results of genotyping and pulsed-field gel electrophoresis suggest the clonal spread of high-level azithromycin-resistant isolates in Taiwan and the circulation of a certain strain through sexual networks, instead of de novo development.

Among the 10 patients infected with high-level azithromycin-resistant N gonorrhoeae, 9 were diagnosed in 2017-18, and 1 was infected in 2013. Geographical spread was throughout Taiwan, and no sexual contact was reported between any of the patients.

The researchers say these findings suggest that Taiwan should consider following the guidance of the British Association for Sexual Health and HIV and recommend a single dose of ceftriaxone intramuscularly as the first choice for treatment of N gonorrhoeae infections, rather than the widely recommended dual therapy of ceftriaxone and azithromycin. 
Jun 24 Antimicrob Agents Chemother abstract

 

European regulators to review new pneumonia antibiotic

Originally published by CIDRAP News Jun 25

Drug maker Nabriva Therapeutics of Dublin announced yesterday that the European Medicines Agency (EMA) has determined that the marketing authorization application (MAA) for the oral and intravenous (IV) formulations of lefamulin is valid.

The validation means that the EMA Committee for Medicinal Products for Human Use will now begin the formal review process for lefamulin, a semi-synthetic pleuromutilin antibiotic for treating community-acquired pneumonia (CAP) in adults. If approved, the drug would receive marketing authorization in all 28 European Union member states, as well as in Iceland, Norway, and Lichtenstein. An opinion is expected within the next 12 to 15 months.

"We are grateful for the EMA's quick validation of our MAA submission and look forward to working with the EMA during the MAA review process.  We are committed to providing European patients with CAP the potential option of short course treatment with IV or oral lefamulin," Nabriva Chief Medical Officer Jennifer Schranz, MD, said in a company press release.

Two phase 3 clinical trials demonstrated that lefamulin was non-inferior to moxifloxacin for the treatment of adults with CAP, and was well-tolerated, the company said.

Nabriva also has NDAs for oral and IV lefamulin currently under review by the FDA. The FDA is expected to complete its fast-tracked review by Aug 19.  
Jun 24 Nabriva Therapeutics press release
Feb 21 CIDRAP News scan on lefamulin NDA approval 

 

UK announces new AMR funding

Originally published by CIDRAP News Jun 25

The British government is awarding £32 million ($40.6 million US) to 10 UK research centers working to combat antimicrobial resistance (AMR), according to a UK Department of Health and Social Care (DHSC) news release.

Among the institutions receiving the funding is Imperial College London, which will receive £4 million ($5.1 million) for the Centre for Antimicrobial Optimisation. The center aims to develop new technologies and innovative approaches to improve the use of antibiotics. Public Health England will receive £5 million ($6.4 million) to develop a model hospital ward to study how hospitals can be designed to improve infection control and reduce transmission of drug-resistant infections.

The funding is part of the British government's 20-year-vision and 5-year national action plan on AMR.

The government also announced that Dame Sally Davies, the UK's outgoing chief medical officer, will become a special UK envoy on AMR.

"The UK should be proud of its world-leading work on AMR," Davies said in the DHSC press release. "We have made tangible progress but it is essential we maintain momentum. I am honoured to have been asked to continue this vital work on behalf of the UK government."
Jun 23 DHSC press release
Jun 24 Imperial College London press release

 

Compliance with CDC stewardship elements linked to higher antibiotic use

Originally published by CIDRAP News Jun 24

In a surprise finding, an analysis of US hospitals today in Infection Control and Hospital Epidemiology has found that meeting all seven of the Centers for Disease Control and Prevention's (CDC's) core elements of hospital antibiotic stewardship programs is associated with higher use of certain antibiotics than meetings six or fewer elements.

The cross-sectional analysis, led by researchers from Virginia Commonwealth University, used responses from a survey that was sent to antibiotic stewardship program (ASP) members at more than 400 hospitals in April 2016. The surveys contained 24 questions regarding aspects of the ASPs and whether they met the CDC's seven core elements, which include leadership, accountability, drug expertise, tracking, actions, reporting, and education. The responses to the survey were then linked to antibacterial use data, measured in days of therapy (DOT) per 1,000 patient-days (PD).

Overall, 211 of 446 hospitals responded to the survey, and antibiotic use was measured in a subset of 57 hospitals that completed the survey and subscribe to a database that tracks inpatient medication use. Of the 57 hospitals, 27 (47%) met all 7 core elements and 30 (53%) met 3 to 6 elements. The analysis found that compliance with all 7 core elements was associated with higher use of broad-spectrum antibiotics for community-acquired infections (145 DOT/1,000 PD vs 124 DOT/1,000 PD, P = .03) and anti–methicillin-resistant Staphylococcus aureus agents (155 DOT/1,000 PD vs 133 DOT/1,000 PD, P = .02).

The findings were unexpected, as the researchers thought that hospitals that met all the core elements would likely use fewer antibiotics. But they note that it's possible that the hospitals that adopted all elements may have required a more robust ASP because of a higher baseline rate of antibiotic use. In addition, they say that the results may have differed if antibacterial use data had been available for all the hospitals that completed the survey.
Jun 24 Infect Control Hosp Epidemiol study

 

Study: Pediatric dengue patients overprescribed antibiotics in Indonesia

Originally published by CIDRAP News Jun 24

A new study in PLOS Neglected Tropical Diseases suggests children at private hospitals in Indonesia are overprescribed antibiotics when seeking treatment for dengue fever.

Dengue is endemic in Indonesia, and infections with the flavivirus are one of the leading causes of pediatric hospitalization. In this retrospective study, researchers looked at the prevalence of antibiotics prescribed to dengue patients under the age of 15 in teaching and private hospitals in the city of Bandung in 2015.

The authors found that the use of antibiotics in private hospitals was mostly inappropriate. A total of 17.5% out of 3,078 cases in both hospitals received antibiotics. Among cases admitted to the teaching hospitals, presumed bacterial upper respiratory tract infection (URTI) and typhoid fever were found in only 1 case (0.6%) and 6 cases (3.4%), respectively, the authors said.

Among 2,902 dengue cases in the private hospital, presumed bacterial URTI was found in 324  cases (11.2%), typhoid fever in 188 cases (6.5%), and urinary tract infection in 18 cases (0.6%). In 67% of URTI cases, broad-spectrum third generation antibiotics were prescribed.

"The use of this agent for URTI is considered as misuse of antibiotics, which can result in detrimental effects for the patients, and the healthcare system, including the emergence of antibiotic resistant pathogens," the authors said. 
Jun 21 PLOS Negl Trop Dis study

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