Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
US hospital data shows rise in resistant UTIs in older patients
An analysis of US hospital data shows that antibiotic resistance in older patients with urinary tract infections (UTIs) nearly doubled from 2009 to 2016, researchers reported yesterday in PLoS One.
In a retrospective observational study using data from the National Inpatient Sample—Healthcare Cost and Utilization Project, researchers from Queens University Belfast, in Northern Ireland, looked at episodes of care involving patients over 65 with a primary diagnosis of UTI. The primary outcomes were the proportion of admissions with antibiotic resistance (based on ICD-9 and ICD-10 codes), factors associated with higher antibiotic resistance, and the impact of antibiotic resistance on all-cause inpatient mortality, discharge destination, length of stay and hospital expenditures.
Over the 8-year period, a total of 546,305 eligible admissions with a primary diagnosis of UTIs were included in the study. The proportion of antibiotic resistance among inpatient episodes those aged 65+ with a primary diagnosis of UTIs increased from 3.64% in 2008 to 6.88% in 2016 (P < 0.001). Factors associated with higher likelihood of having an antibiotic-resistant UTI included higher age-adjusted Deyo-Charlson Comorbdity Index (ACCI) score (odds ratio [OR], 1.06, 95% confidence interval [CI], 1.06 to 1.07) and admissions to hospitals in urban areas (OR, 1.07; 95% CI, 1.00 to 1.15).
Admissions with antibiotic resistant UTIs were more likely to be discharged to healthcare facilities (e.g. care homes) compared to those without antibiotic resistance (OR, 1.81; 95% CI, 1.75 to 1.86), had increased length of stay (1.12 days longer; 95% CI, 1.06 to 1.18), and had higher hospital costs ($1,259 USD; 95%CI, $1,178 to $1,340). Resistance due to methicillin-resistant Staphylococcus aureus was specifically associated with increased hospital mortality (OR, 1.33; 95% CI, 1.15 to 1.53).
"Our findings indicate a considerable impact of this issue on clinical and economic outcomes," the authors of the study write. "These relationships and their implications for the care homes to which patients are likely discharged warrant further research."
Oct 3 PLoS One study
Accelerate Diagnostics touts data on rapid diagnostic test
Originally published by CIDRAP News Oct 3
Accelerate Diagnostics presented three studies today at IDWeek 2019 in Washington, DC, that show promising results for its rapid phenotypic susceptibility test, according to a company press release.
In the RAPIDS-GN randomized controlled trial, conducted at Mayo Clinic and the University of California, Los Angeles, investigators reported that the Accelerate PhenoTest BC kit, when compared with legacy testing methods in gram-negative bacteremia patients, shortened reporting time to first gram-negative antibiotic change a full 24 hours sooner than legacy methods (17.4 vs 42.1 hours) and reporting time to any antibiotic change 6 hours sooner (8.6 vs 14.9 hours).
In a single-center study conducted by researchers at the University of Arkansas for Medical Sciences, use of the Accelerate Pheno system was associated with a statistically significant decrease in time on broad-spectrum gram-positive antibiotics of 23.3 hours and a decrease in time on broad-spectrum gram-negative antibiotics of 38.4 hours. Hospital length of stay was also reduced.
Data from a study conducted at the University of Iowa Hospitals and Clinics showed that implementation of Accelerate Pheno paired with antimicrobial stewardship team review resulted in early optimization of antibiotic therapy, with the highest impact seen in patients with resistant gram-negative infections.
"We are thrilled to see these data, which demonstrate conclusively that the Accelerate PhenoTest BC kit positively impacts clinical outcomes across a diverse set of institutions and patient populations," said Romney Humphries, PhD, Chief Scientific Officer of Accelerate Diagnostics. "The studies show an improvement in antibiotic use, a necessary factor for lowering the risk of multidrug-resistant infections and in preserving the patient's vital functions, while also improving the hospital's bottom line by reducing patient length of stay."
Oct 3 Accelerate Diagnostics press release
Data show promise for novel antibiotic against gram-negative pneumonia
Originally published by CIDRAP News Oct 3
Data presented today at IDWeek by Shionogi & Co researchers reveal that its investigational drug cefiderocol, a novel siderophore cephalosporin that has shown activity against a broad range of gram-negative bacteria, was non-inferior to meropenem in patients who had hospital-acquired pneumonia caused by gram-negative bacteria.
In the study, 148 patients were randomized to receive cefiderocol and 150 to meropenem. Illnesses were typically severe; 60% required mechanical ventilation, and a third had previous treatment failure. Patients received high doses (2 grams) of the drugs every 8 hours.
All-cause mortality at 14 days was similar for cefiderocol (12.4%) versus merpoenem (11.6%), as was clinical cure (64.8% vs 66.7%), and microbiological eradication (47.6% vs 48.0%).
Tsutae "Den" Nagata, MD, Shionogi's chief medical officer, in a company news release, said the findings "provide meaningful evidence that cefiderocol has the potential to be an effective treatment option for severely ill hospitalized patients with pneumonia….Recently, several new antibiotics have been introduced to address some carbapenem-resistant infections, but they do not address all resistant Gram-negative pathogens. Clinicians are in urgent need of novel therapeutic approaches to overcome the multiple resistance mechanisms that make these strains so difficult to treat."
The researchers recorded no unexpected safety issues with the new drug.
Cefiderocol—a cephalosporin—has a novel method of penetrating the tough outer membrane of gram-negative bacteria, including multidrug-resistant strains. It has been fast-tracked for assessment by the US Food and Drug Administration, which has assigned an action date of Nov 14 to the drug. It showed promising results against complicated urinary tract infections in a study published last year.
Oct 3 IDWeek abstract
Oct 2 Shionogi news release
Oct 26, 2018, CIDRAP News story "Fast-tracked antibiotic shows promise in phase 2 trial"
FDA grants priority review for fidaxomicin for C diff in kids
Originally published by CIDRAP News Oct 2
Merck announced today that the FDA has accepted a New Drug Application (NDA) and a supplemental NDA for use of different fidaxomicin (Dificid) formulations in treating Clostridioides difficile infections in children ages 6 months and older.
In a news release, Merck, of Kenilworth, New Jersey, said the NDA is for the oral suspension of the drug and the supplemental NDA is a new indication for use of tablets and oral suspension. The FDA has granted priority review for both applications, and the Prescription Drug User Fee Act (PDUFA) date for both applications is Jan 24, 2020. The FDA granted Orphan Drug Designation for the investigational pediatric indication in 2010.
Nicholas Kartsonis, MD, Merck's senior vice president for clinical research, infectious diseases, and vaccines, said in the release that evidence suggests the incidence of C difficile diarrhea in hospitalized children is increasing. "The filings for the pediatric indication for the new investigational oral suspension formulation of DIFICID, as well as for DIFICID tablets, underscore Merck's focus and dedication to developing infectious disease treatments for those with unmet needs," he said.
The company said the supplemental NDA is based mainly on findings of a phase 3 study that was presented at IDWeek 2018 in San Francisco.
Fidaxomicin is a macrolide antibacterial medication currently indicated for adults for treating C diff diarrhea. In 2018 the Infectious Diseases Society of America recommended fidaxomicin as a first-line therapy for treating C diff infections, the first time those recommendations addressed pediatric treatment of the disease.
Oct 2 Merck press release
VA study finds negative MRSA nasal swabs effective at ruling out infection
Originally published by CIDRAP News Oct 1
A study today in Clinical Infectious Diseases indicates that nasal screening of patients for MRSA colonization has a high negative predictive value (NPV) for ruling out MRSA infection and could be a powerful antibiotic stewardship tool.
In a retrospective study conducted across Veterans Affairs (VA) medical centers nationwide, researchers from the VA Western New York Healthcare System looked at data from all VA patients who were screened for MRSA colonization via the nares (nostrils) from 2007 (when the screening policy was initiated in VA medical centers) to 2018. They then evaluated the subsequent clinical cultures collected within 7 days of the nares swab for the presence of MRSA. The aim was to determine whether the absence or presence of MRSA nasal carriage predicts the presence of MRSA in clinical cultures.
Nasal screening on admission was done in 96.5% of patients. The cohort yielded 561,325 clinical cultures from a variety of anatomical sites, mainly urine (40%), wound (24.7%), respiratory (16.2%), and blood (12.5%). A positive screen for MRSA nares occurred in 22.9% of patients, and MRSA was identified in 8.3% of subsequent clinical cultures. The sensitivity and specificity of MRSA nasal screening for positive MRSA clinical culture were 67.4% and 81.2%, respectively, and the NPV of a negative MRSA nares swab for ruling out MRSA infection was 96.5%. The positive predictive value was only 24.6%.
The NPV was highest for ruling out MRSA in urinary cultures (99.2%), followed by intra-abdominal cultures (98.5%), blood cultures (96.5%), respiratory cultures (96.1%), and wound cultures (93.1%).
The authors of the study conclude, "This study suggests that a negative MRSA nares swab, taken within 7 days of culture, is useful to predict the absence of MRSA in a subsequent clinical culture. This information may be used as a stewardship tool to avoid the use of or de-escalate anti-MRSA therapy. It is not, however, appropriate to use MRSA nares as a tool to predict current infection."
Oct 1 Clin Infect Dis abstract
High global MDR prevalence, death noted in A baumannii pneumonia
Originally published by CIDRAP News Oct 1
A systematic review and meta-analysis of data from 29 countries highlights the global burden and severity of Acinetobacter baumannii causing nosocomial pneumonia, researchers from Australia and Malaysia reported yesterday in The Journal of Infection.
Among the 6,445 studies and reports screened from four databases, the researchers identified 126 relevant studies on A baumannii in patients with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). The review aimed to provide a global picture of the prevalence of multidrug-resistant A baumannii (MDRAB) in HAP and VAP, and the associated mortality rate. While A baumannii is known to be intrinsically highly resistant to many antibiotics, and numerous studies have reported on the prevalence of MDRAB in HAP and VAP, those studies have been geographically limited.
A meta-analysis of the 126 studies found that the overall prevalence of multidrug resistance among A baumannii causing HAP and VAP was 79.9%, with the highest reported prevalence in Central America (100%), Latin America and the Caribbean (100%), and Western Europe (100%). The regions with the lowest prevalence were Eastern Europe (70.6%), North America (69.8%), and Eastern Asia (64.6%). Among countries, the prevalence ranged from 56% (Argentina) to 100% (Mexico, Cuba, Uruguay, Nepal, Pakistan, Lebanon, Qatar, and Croatia).
The overall mortality estimate pooled from 27 studies was 42.6%, with the highest reported rates in Western Asia (56.2%), Southern Europe (55.7%), and Northern Africa (53.3%). The lowest reported mortality rates were in Western Europe (33.3%), Southeast Asia (31.9%), and North America (28.6%). The mortality rate among countries ranged from 28% (Iran) to 68% (Greece).
The authors of the study say the differences in MDRAB prevalence likely reflect the level of urbanization, sanitation, poverty, and variation in medical resources.
"It is clear that the burden of MDRAB in HAP and VAP and the mortality rate is high," they write. "Continuous monitoring of drug resistance and strict infection control are recommended for the prevention and control of MDRAB in HAP and VAP."
Sep 30 J Infect abstract
Targeted stewardship may reduce post-discharge fluoroquinolones
Originally published by CIDRAP News Sep 30
Researchers conducting a Veterans Health Administration (VHA) study involving 122 hospitals have determined that a targeted inpatient fluoroquinolone stewardship program (ASP) is tied to improved fluoroquinolone prescribing at hospital discharge, with UTIs and chronic obstructive pulmonary disease (COPD) most often associated with inappropriate prescribing of the drugs, according to findings published in Clinical Infectious Diseases.
The researchers analyzed data on more than 1.7 million patients from 2014 through 2016 among the VHA hospitals and on 1.73 million fluoroquinolone days of therapy (DOTs). Of that total, 39% of DOTs were prescribed for inpatients, and the rest were for use post-discharge.
The team also assessed two ASP approaches for optimizing fluoroquinolone prescribing— prospective audit-and-feedback (PAF) and restrictive policies (RP)—as well as no strategy. They assessed the three approaches in three hospitals each, and assessed 125 patients in each hospital.
The authors used risk-adjusted analysis to determine that post-discharge fluoroquinolone exposure differed significantly only between RP and no-strategy sites (3.8% vs 9.3%, P = 0.012). They found no significant difference in fluoroquinolone exposure between PAF and no-strategy hospitals. About 31% of all post-discharge fluoroquinolones were prescribed for patients who did not receive them while an inpatient, and most common diagnoses among those prescribed the antibiotics at discharge were UTI (18.7%) and COPD (14.5%).
The investigators also report that post-discharge fluoroquinolone prescription was deemed inappropriate by selection or duration in 154 (41.1%) of 375 patients, with the rate varying from 35.2% in hospitals with a targeted ASP versus 52.8% in no-strategy hospitals. The scientists report that the difference between PAF (29.6%) and RP (40.8%) hospitals did not reach statistical significance (P =0.06). Inappropriate post-discharge fluoroquinolones were flagged for 23 (79.3%) of 29 COPD patients and for 32 (55.2%) of 58 UTI patients.
The authors conclude, "Our findings suggest that stewardship efforts to minimize and improve fluoroquinolone-prescribing should also focus on antimicrobial-prescribing at hospital discharge."
An accompanying commentary adds, "Successful implementation of [antibiotic stewardship] at this critical transition point will need to leverage and engage frontline providers, staff, pharmacists, case management, nurses, and the entire care team."
Sep 28 Clin Infect Dis study
Sep 28 Clin Infect Dis commentary
Phase 3 trial for new gonorrhea antibiotic to launch
Originally published by CIDRAP News Sep 30
Biopharmaceutical company Entasis Therapeutics and the nonprofit Global Antibiotic Research and Development Partnership (GARDP) today announced the initiation of a global phase 3 clinical trial for zoliflodacin, a new antibiotic for treating uncomplicated gonorrhea.
The trial aims to enroll approximately 1,000 patients with urogenital gonorrhea from sites in the United States, Netherlands, Thailand, and South Africa. Patients will be randomized 2:1 to receive either zoliflodacin or a combination of ceftriaxone and azithromycin, the current first-line treatments for uncomplicated gonorrhea.
Developed by Entasis, of Waltham, Massachusetts, zoliflodacin is a single-dose oral antibiotic with a mechanism of action that differs from current therapies. In a phase 2 trial involving 179 patients from sexual health clinics in Louisiana, Alabama, Indiana, North Carolina, and Washington, the drug was found to be highly effective in treating urogenital and rectal gonorrhea and was well-tolerated. But it was much less effective in treating pharyngeal gonorrhea.
The trial is critical, because the World Health Organization (WHO) has warned that rising resistance to ceftriaxone and azithromycin threatens the ability to treat the sexually transmitted infection, and that failure to develop new drugs could result in widespread treatment failure. Untreated gonorrhea can lead to pelvic inflammatory disease, ectopic pregnancy, infertility, and increased HIV risk.
Under the agreement with Entasis, GARDP is responsible for the phase 3 trial and pharmaceutical development activities to support regulatory approval and market availability, and has commercial rights to zoliflodacin in up to 168 low- and middle-income countries.
"The initiation of the phase 3 trial of zoliflodacin is an important milestone and brings hope for people affected by this disease. Our partnership with Entasis is critical for preventing the dire scenario of untreatable gonorrhoea and controlling this infection," GARDP Executive Director Manica Balasegaram, MRCP, MSc, said in a GARDP press release. "The global nature of the trial, across four continents, represents our commitment to ensuring this treatment is available to anyone who needs it, wherever they live."
The WHO estimates that 87 million new gonorrhea cases occur each year, and the rate is rising.
Sep 30 GARDP press release
Rapid viral testing fails to reduce antibiotics, hospital stays in Finnish trial
Originally published by CIDRAP News Sep 30
The results of a randomized controlled clinical trial conducted in Finland show that rapid viral testing did not reduce antibiotic consumption or shorten hospital stays in acutely ill adults, Finnish researchers report in Clinical Microbiology and Infection.
The single-center study involved patients with respiratory symptoms, fever, chest pain, or poor general condition in the emergency unit of a tertiary hospital in Finland who were randomized 1:1 into two groups: a rapid viral diagnostics group (the intervention group) and a delayed viral diagnostics group (the control group). The attending physician received the viral results for the intervention group within 24 hours and the results from the control group within 7 days. Nasal swab samples were analyzed using a multiplex real-time polymerase chain reaction (PCR) detection method. The primary outcomes were duration of hospitalization and antibiotic consumption.
Of the 998 randomized patients, 841 (84%) had respiratory symptoms at study entry. A respiratory virus was detected in 175 patients—94 (19%) in the intervention group and 81 (16%) in the control group.
Among the 684 patients admitted to the hospital, the mean duration of hospitalization was 4.2 days (standard deviation [SD], 5.4) in the intervention group and 4.1 days (SD, 4.9) in the control group (difference, 0.1 days; 95% confidence interval [CI], -0.5 to 0.6, P = 0.810). Among the 639 patients who received antibiotic treatment, the mean days on antibiotics were 11.3 days (SD 12.6) in the intervention group and 10.4 days (SD, 11.4) in the control group (difference 0.9; 95% CI, -0.6 to 2.4, P = 0.235). There was no statistically significant difference between the two groups.
The researchers note that the results are in line with several other randomized studies conducted in recent years that have tested whether improved diagnostics could reduce antibiotic consumption in adult patients with respiratory illness. They suggest that one of the reasons these interventions have failed in that aim may be clinicians' anxiety in the face of poor outcomes, especially in older patients and other high-risk groups.
Sep 28 Clin Microbiol Infect study