ASP Scan (Weekly) for Aug 12, 2022

Antibiotic increase during flu season
TB drug availability, costs in Europe
TB vaccine effectiveness
Healthcare-associated infections in India
Pan-resistant fungal infection
Antibiotic stewardship survey
ASP benefits at peds urgent cares

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

Study shows link between flu activity and antibiotic use in hospitals

A retrospective analysis of US hospital data found that the use of certain inpatient antibiotics was strongly associated with influenza activity during the 2015 through 2019 viral respiratory seasons, researchers reported yesterday in Antimicrobial Stewardship & Healthcare Epidemiology.

To evaluate changes in inpatient antibiotic use (IAU) over time and possible associations between influenza rates and IAU, researchers with Becton, Dickinson & Co (BD) analyzed data on adult hospital patients from the BD Insights Research Database, which includes large and small hospitals across the United States. They looked at community influenza rates and IAU for commonly prescribed oral and intravenous antibiotics, calculated as days of therapy (DOT) per 1,000 patient-days.

Among the 239 facilities contributing data, extended-spectrum cephalosporins (ESC), specific anti–methicillin-resistant Staphylococcus aureus (MRSA) drugs, and beta-lactam inhibitor combinations (BLICs) had the highest IAU rates from 2015 through 2019 (average of 125, 95, and 94 DOT per 1,000 patient-days, respectively). Ascending trends over time were observed for ESCs, BLICs, macrolides, and tetracyclines. Seasonal changes in IAU were significant for BLICs, macrolides, tetracyclines, specified anti-MRSA drugs, and lipopeptides.

In multivariate analyses that controlled for geographic regions and hospital-level factors, influenza rates were significantly associated with IAU for ESCs, specified anti-MRSA drugs, macrolides, fluoroquinolones, tetracyclines, and lipopeptides. The researchers found no association between influenza rates and IAUd for BLICs, carbapenems, and "other" antibiotics.

The authors of the study note that while patients with influenza-like respiratory symptoms are treated empirically with antibiotics because of concerns about secondary bacterial infections, many antibiotics showing this association are often prescribed and recommended for community-acquired pneumonia (CAP), and that unsupported antibiotic use in hospitalized patients with CAP is common.

They concluded, "Information on IAU influenced by influenza activity may be useful in guiding infection prevention and control measures, including rapid diagnostic testing and vaccination campaigns for influenza and other respiratory viruses, and in determining policies, strategies, and programs for antimicrobial stewardship efforts to reduce inappropriate IAU during influenza season."
Aug 11 Antimicrob Steward Healthc Epidemiol study


Study: Treatment for drug-resistant TB limited, costly in Europe

Originally published by CIDRAP News Aug 11

A survey of tuberculosis (TB) treatment centers in Europe found the availability of drug susceptibility testing (DST) for new and repurposed TB drugs in Europe is severely limited, drugs and regimens for drug-resistant TB are limited, and treatment costs for drug-resistant TB are very high, according to a study published this week in Clinical Microbiology and Infection.

For the study, a team of researchers with the Tuberculosis Network European Trials group (TBNET) surveyed 43 TB treatment centers in 40 countries in the World Health Organization (WHO) European region, gathering data on DST, TB drug availability, and cost. They focused on treatment regimens for drug-susceptible TB (DS-TB), multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB), extensively drug-resistant TB (XDR-TB), and pre-XDR-TB.

For WHO Group A drugs (levofloxacin/moxifloxacin, bedaquiline, and linezolid) the frequency of countries with availability of phenotypic DST was as follows: 30/40 (75%) for levofloxacin, 33/40 (82%) for moxifloxacin, 19/40 (48%) for bedaquiline and 29/40 (72%) for linezolid. Overall, 36/43 (84%) and 24/43 (56%) of countries had access to bedaquiline and delamanid, which while only 6/43 (14%) had access to rifapentine. Treatment of patients with XDR-TB with a regimen including a carbapenem was available in only 17/43 (40%) of the countries.

The median cost of regimens for DS-TB, MDR/RR-TB (shorter regimen, including bedaquiline for 6 months), and XDR-TB (including bedaquiline, delamanid, and a carbapenem) were €44 ($45.50 US), €764 ($789 US), and €8,709 ($9,004 US), respectively, in middle-income countries, and €280 ($289 US), €29,765 ($30,733 US), and €217,591 ($224,963 US) in high-income countries.

The authors of the study note that the lack of DST for drugs like bedaquiline and linezolid will result in an inability to detect patients with XDR-TB who carry the worst prognosis, while the high cost of the shorter regimen for MDR/RR-TB will have enormous cost implications for countries with a high burden of drug-resistant TB. They say the data provided by the study highlight the need for "urgent action."

"Strong political support and coordinated action from supranational institutions, countries and their TB programmes, non-governmental organizations and civil society is needed to ensure access to the best standard of care to patients affected by TB," they wrote.
Aug 9 Clin Microbiol Infect study


TB vaccine only effective in children under 5

Originally published by CIDRAP News Aug 11

The bacille Calmette-Guerin (BCG) vaccine, when given at birth, is effective at preventing TB in children under 5 but ineffective in adolescents and adults, researchers reported in The Lancet Global Health.

To estimate the effectiveness of the BCG vaccine, which is around 100 years old and one of the most widely used vaccines globally, a team led by researchers from Boston University School of Public Health analyzed individual-level data from 26 longitudinal studies that included more than 68,000 participants exposed to TB from 1998 to 2018. The primary outcome was a composite of prevalent (diagnosed at or within 90 days of baseline) and incident (diagnosed more than 90 days after baseline) TB in exposed contacts. Secondary outcomes were pulmonary TB, extrapulmonary TB, and mortality.

Among 68,552 participants, 1,309 (2.6%) of 49,686 BCG-vaccinated participants developed TB, compared with 473 (2.5%) of 18,866 unvaccinated participants. The overall effectiveness of BCG vaccination against all forms of TB was 18% (adjusted odds ratio [aOR], 0.82: 95% confidence interval [CI], 0.74 to 0.91). When stratified by age, BCG vaccination only significantly protected against all TB in children younger than 5 years (aOR, 0.63; 95% CI, 0.49 to 0.81).

BCG vaccination significantly protected against pulmonary tuberculosis among all participants (916 [2.2%] in 41,119 vaccinated participants vs 334 [2.1%] in 16,161 unvaccinated participants; aOR, 0.81; 95% CI, 0.70 to 0.94) but not against extrapulmonary tuberculosis (106 [0.3%] in 40,318 vaccinated participants vs 38 [0.2%] in 15,865 unvaccinated participants; aOR, 0.96; 95% CI, 0.65 to 1.41). In the four studies with mortality data, BCG vaccination was significantly protective against death (aOR, 0.25; 95% CI, 0.13 to 0.49).

The authors say that while the findings affirm the value of BCG vaccination in children in TB-endemic settings, they also highlight the need for new TB vaccines.

"These results suggest that infant BCG vaccination, although important to young children who are at high risk of tuberculosis, does not prevent adult-type cavitary tuberculosis and is therefore insufficient to impede the tuberculosis epidemic, providing further evidence that novel vaccines are urgently needed," the study authors concluded. They also suggest that until new TB vaccines are developed, children over 10 and adults should receive a BCG booster.
Sep 2022 Lancet Glob Health study


Hospital data from India show high rate of healthcare infections, antibiotic resistance

Originally published by CIDRAP News Aug 10

Data from a healthcare-associated infection (HAI) surveillance network in India shows high rates of bloodstream and urinary tract infections (UTIs) and very high levels of antibiotic resistance, researchers reported in The Lancet Global Health.

The data come from a network of 26 public and private tertiary-level hospitals in India created to implement HAI surveillance using standardized HAI surveillance methods that more accurately reflect resources available in Indian hospitals. Each hospital enrolled at least one intensive care unit (ICU) treating adult patients, one ICU treating adult surgical patients, and one pediatric ICU, and collected surveillance data on bloodstreams infections and UTIs, along with pathogen and antibiotic susceptibility test results. Neonatal ICUs reported only bloodstream infections.

From May 2017 through October 2018, the hospitals reported 2,622 bloodstream infections and 737 UTIs from 89 ICUs. Central line-associated bloodstream infection rates were highest in neonatal ICUs (more than 20 per 1,000 central line days), and catheter-associated UTI rates were highest in pediatric medical ICUs (4.5 per 1,000 urinary catheter days). Hospitals identified 2,828 pathogens in the 2,622 bloodstream infections reported and 809 in the 737 UTIs reported. Klebsiella spp (24.8%) were the most frequent pathogens reported in bloodstream infections, followed by Acinetobacter spp (21.3%), and Candida spp (29.4%) were the most frequently reported pathogens in UTIs.

Carbapenem resistance was common in Gram-negative infections, occurring in 72.4% of bloodstream infections and 76.3% of UTIs caused by Klebsiella spp, 77.2% of bloodstream infections and 75.7% of UTIs caused by Acinetobacter spp, 63.7% of bloodstream infections and 71.9% of UTIs caused by Pseudomonas spp, and 58% of bloodstream infections and 62% of UTIs caused by Escherichia coli.

"Healthcare-associated bloodstream infections and UTIs, particularly antibiotic-resistant infections, are major problems across network hospitals, and focused efforts targeting prevention of priority HAIs are underway," the study authors wrote. "Data produced by this network can be used as a foundation for developing a better understanding of the burden of HAIs across India."
Sep 2022 Lancet Glob Health study


Report describes pan-resistant, environmentally-acquired fungal infection

Originally published by CIDRAP News Aug 10

A case report published today in Emerging Infectious Diseases describes a fatal, pan-resistant fungal infection in an immunocompromised patient in the United States.

The infection was caused by Aspergillus fumigatus, the most common cause of invasive aspergillosis, a life-threating fungal infection that occurs when A fumigatus spores in the environment are inhaled. The patient was a 65-year-old man undergoing treatment for acute myeloid leukemia who was hospitalized for progressive graft-versus-host disease following an allogeneic stem cell transplant.

After 23 days of hospitalization and onset of hypoxemic respiratory failure, the patient was diagnosed with multifocal pneumonia, and bronchial cultures were positive for A fumigatus. The patient died on hospital day 28 from sepsis. Subsequent antifungal susceptibility testing and DNA sequence analysis showed resistance to the triazole antifungals itraconazole and voriconazole, with an environmentally-acquired gene mutation that can cause pan-triazole resistance.

The authors of the report say that while triazole resistance can occur through exposure to long-term triazole therapy, it's also been linked to agricultural use of triazole fungicides, which are chemically similar to triazole antifungals. They note that reports of environmentally acquired triazole-resistant A fumigatus infections are increasing, and say systematic clinical and environmental surveillance for triazole resistance is needed in the United States to determine the spread of the fungus and guide clinical treatment. Use of triazole fungicides by US farmers increased fourfold from 2006 to 2016.

"This report underscores the potential severity of triazole-resistant A. fumigatus infections in immunocompromised persons," they wrote. "Furthermore, clinicians should consider the possible presence of drug-resistant A. fumigatus in patients with invasive aspergillosis who do not improve with first-line therapy."
Aug 10 Emerg Infect Dis research letter


Survey: ID doctors view antimicrobial stewardship programs positively

Originally published by CIDRAP News Aug 9

A survey of US pediatric infectious disease (ID) physicians found highly favorable opinions of antimicrobial stewardship programs (ASP), both among ASP and non-ASP doctors, researchers reported yesterday in Infection Control & Hospital Epidemiology.

Overall, 176 of 359 (49%) pediatric ID physicians surveyed responded. Among the respondents, 94% of ASP physicians and 81% of non-ASP physicians agreed that the ASP at their institution had improved appropriate antibiotic prescribing in the previous 2 years, while 91% of ASP physicians and 84% of non-ASP physicians disagreed with the statement that the ASP had been too focused on reducing antibiotic costs, compromising patient care, with a larger proportion of ASPs strongly disagreeing.

Most physicians in both groups were not concerned that ASPs make recommendations without seeing patients and were either neutral or not concerned about the impact on prescriber autonomy, unintended consequences of guidance, decreases in prescriber efficiency, or delays in antibiotic initiation.

The study authors note that since the response rate was less than 50%, the findings may not be representative of all US pediatric ID physicians. They add that studies to better characterize ASP practices, evaluate patient outcomes, and improve ASP collaborations with ID physicians are needed.
Aug 8 Infect Control Hosp Epidemiol abstract


ASP improved antibiotic prescribing at pediatric urgent care centers

Originally published by CIDRAP News Aug 8

Implementing an ASP at pediatric urgent care centers significantly improved appropriate antibiotic dosing and duration, researchers from Missouri reported in a recent issue of the American Journal of Infection Control.

Urgent care centers have some of the highest rates of unnecessary antibiotic prescribing in outpatient settings. For the study, the researchers examined prescribing patterns at three Kansas City, Missouri, area pediatric urgent care (PUC) clinics, plus one in a rural area.

They assessed encounters for six different conditions, with an eye toward comparing antibiotic prescribing rates before the ASP was implemented, from July 2017 to July 2018, and after it was implemented, August 2018 to December 2020. The conditions included ear infection, group A streptococcal pharyngitis, community-acquired pneumonia, urinary tract infection, and skin and soft tissue infections.

Some of the elements of the ASP program included semi-annual clinician education sessions, a handbook, and prescription folders for common diagnoses in the electronic health record.

Over the study period, there were 35,917 patient encounters. The percentage of prescriptions with the recommended agent at the recommended dose and duration increased from 32.7% to 52.4%, with the most substantial changes seen in appropriate duration and dose. Group A strep pharyngitis was the only diagnosis that didn't improve by at least one measure, though the authors pointed out that dosing for the condition is standard.

The team saw some seasonal fluctuations reflecting higher antibiotic prescribing rates in winter. They noted that prescribing increased in the last few months of the study, raising the possibility that the pandemic may have contributed to fluctuations, including for community-acquired pneumonia.

Also, they noted that PUC clinicians often prescribed antibiotics at lower-than-recommended doses, which contributes to treatment failures and partially treated infections.

They wrote that they focused similar ASPs on improving the quality of prescribing rather than restricting use, which may have made clinicians more willing to adopt changes.
Aug 5 Am J Infect Control abstract

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