Stewardship programs tied to reduced initiation, shorter duration of antibiotics in newborns

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Baby in NICU
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A review and meta-analysis found that neonatal antimicrobial stewardship programs (ASPs) are associated with reduced initiation and duration of antibiotics use in newborns, with no increase in adverse events, researchers reported today in Pediatrics.

The review, conducted by researchers with the University of Toronto and the University of Alberta, analyzed data from 70 studies (44 cohort and 26 observational studies) involving 350,000 newborns that evaluated ASP impacts in neonatal intensive care units (NICUs) and postnatal ward settings. Antibiotics are the most frequently administered drugs in NICUs, and empiric use of broad-spectrum antibiotics in NICUs is a common practice to prevent infection or halt the progression of sepsis. But overuse of antibiotics in newborns has been associated with increased neonatal mortality and other adverse effects, as well as an increase in drug-resistant organisms.

Overall positive impact

Most studies included in the meta-analysis evaluated interventions aimed at reducing antimicrobial initiation and duration, and had significant heterogeneity in terms of ASP interventions, population settings, and outcome definitions.

Moderate-certainty evidence revealed a significant reduction in antimicrobial initiation in NICU (pooled risk difference [RD], 19%; 95% confidence interval [CI], 14% to 24%) and combined NICU and postnatal ward settings (pooled RD, 8%; 95% CI, 6% to 10%), days of therapy (pooled RD, 20%; 95% CI, 10% to 30%), length of therapy (pooled RD, 1.82 days; 95% CI, 1.09 to 2.56 days), and use of antimicrobial agents for more than 5 days (pooled RD, 9%; 95% CI, 3% to 15%). 

Low-certainty evidence revealed a reduction in drug resistance prevalence, costs, and favorable sustainability metrices, without an increase in sepsis-related mortality or the re-initiation of antimicrobial agents. 

"Our review highlights the overall positive impact of ASP interventions in restricting the initiation and duration of antimicrobial use in neonates, with quantifiable measures," the study authors wrote. "Future prospective studies are warranted to evaluate drug resistance and economic burden."

CDC urges travelers to Saudi Arabia to be current with meningococcal vaccines

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The US Centers for Disease Control and Prevention (CDC) today issued a health alert and a level 1 travel alert about meningococcal disease in travelers to Saudi Arabia, especially those taking part in pilgrimage activities.

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The alerts follow a recent notification from the European Centre for Disease Prevention and Control. Of 12 recent cases in the United States and Europe due to Saudi Arabia travel, 10 were in people who traveled to Saudi Arabia and 2 were close contacts, the CDC said in its Health Advisory Network notice.

Most cases were caused by serogroup W, but one US case was due to serogroup C and another involved an unknown serotype. Most patients were unvaccinated, and isolates from three patients suggest resistance to ciprofloxacin. 

Travel notice details vaccine recommendations, Saudi requirements

Also, the CDC today posted a level 1 travel notice, the lowest designation that urges travelers to practice usual precautions. It urged people traveling to the Hajj pilgrimage in Saudi Arabia, scheduled for June 14 to June 19, or the Umrah pilgrimage, to ensure that they are up to date with all routine and travel-related vaccines, including meningococcal disease. 

The agency added that Saudi Arabia requires all travelers 1 year and older arriving for pilgrimages to show proof that they have received quadrivalent (four-strain) vaccine at least 10 days prior to travel.

DR Congo mpox outbreak poses global threat of deadlier clade

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An ongoing outbreak of the clade 1 mpox virus in the Democratic Republic of the Congo (DRC) poses a threat to the United States, authors write in Morbidity and Mortality Weekly Report. Clade 1 is more deadly and severe than the clade 2 virus that caused a global outbreak among men who have sex with men (MSM) in 2022. 

Both clades of the virus are endemic in the DRC, but the country noted an uptick in clade 1 cases in 2023 and 2024, with 19,919 suspected cases reported and 975 (4.9%) deaths. Cases are spreading both among traditional household transmission routes, and among sexual networks, including MSM and sex workers. 

Two thirds of cases in kids under 15

Of note, a large proportion of the current outbreak is among children ages 15 and under, representing 67% of suspected cases and 78% of suspected deaths. Children aged 12 to 59 months accounted for 28% of all suspected cases.

Beginning December 7, 2023, the US Centers for Disease Control and Prevention urged clinicians to consider clade 1 infections in persons with mpox signs and symptoms who had recently been in DRC, and conduct clade-specific testing for those patients.

To date, no cases of clade I mpox have been reported in the United States or in any countries where the virus is not endemic.

"To date, no cases of clade I mpox have been reported in the United States or in any countries where the virus is not endemic. However, given the documented sexual transmission of clade I MPXV in DRC, persons engaging in certain sexual behaviors (e.g., MSM with multiple sexual partners and sex workers) might be at increased risk if clade I mpox is introduced into the United States," said authors. 

The authors warned that 19 recent cases of clade 1 detected in DRC's neighboring Republic of the Congo suggests the cases in the DRC, "pose a new risk for global spread if the virus is not urgently contained.

"In addition to preparing for the possibility of spread beyond DRC, support to DRC from global partners is needed as the country works to increase testing and surveillance for clade I MPXV."

Beta-lactam allergies linked to higher risk of resistant infections, but not mortality

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A longitudinal study of more than 20,000 patients in a regional healthcare system found that beta-lactam (BL) allergies were not associated with increased risk of death but were associated with increased risk of antibiotic-resistant infections, researchers reported late last week in JAMA Network Open.

Using electronic health record data on patients diagnosed as having sepsis, pneumonia, or urinary tract infection at the University of Pittsburgh Medical Center from 2007 through 2018, researchers assessed all-cause mortality among those patients with a documented BL allergy, which is the most common drug allergy worldwide but also the most reported in error. Secondary outcome included infection with methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and Clostridioides difficile, and the severity and occurrence of acute kidney injury (AKI).

Of the 20,092 patients (60.9% female; mean age, 62.9 years) included in the study, 4,211 (21%) had a documented BL allergy and 15,811 (79%) did not. Patients with a BL allergy were more likely to be female (69.1% vs 58.7%), older (64.2 years vs 62.6 years), and White (79.1% vs 75.7%) than those without. Baseline clinical characteristics did not differ significantly between the two groups.

44% increased risk of MRSA infection

While patients with documented BL allergy had higher rates of unadjusted all-cause mortality, multivariable analysis found no significant increase in the odds of mortality (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.96 to 1.09) compared with no documented BL allergy. But BL allergies were associated with increased odds of MRSA infection (OR, 1.44; 95% CI, 1.36 to 1.53), VRE infection (OR, 1.18; 95% CI, 1.05-1.32), and the pooled rate of the three evaluated antibiotic-resistant infections (OR, 1.33; 95% CI, 1.30 to 1.36).

No significant increase in risk of C difficile infection alone (OR, 1.04; 95% CI, 0.94 to 1.16), stage 2 and 3 AKI (OR, 1.02; 95% CI, 0.96 to 1.10), or stage 3 AKI (OR, 1.06; 95% CI, 0.98 to 1.14) was observed.

The researchers say the association with increased risk of antibiotic-resistant infections suggests further research into the long-term impact of BL allergies is needed. They also call on health systems to emphasize accurate allergy documentation to reduce unnecessary BL avoidance.

Data show rising antibiotic resistance with repeat urinary tract infections

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Urinary tract infection testing
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Over half (57%) of index urinary tract infections (UTIs) treated at a California healthcare system were caused by bacteria resistant to at least one antibiotic class, while 13% were resistant to three or more classes, with respective proportions rising to 65% and 20% with subsequent infections.

These findings, published in the Journal of Infectious Diseases, show the importance of continually monitoring UTI recurrences and antibiotic susceptibility patterns to guide treatment decisions, the Kaiser Permanente Southern California–led research team said.

The researchers assessed the number of characteristics of subsequent UTIs in a patient cohort diagnosed as having an uncomplicated UTI (uUTI) from January 2016 to December 2020, with follow-up through 2021.

Need for continuous susceptibility monitoring

Of 148,994 patients diagnosed as having a uUTI, 19% had a subsequent culture-confirmed infection after a median of 300 days. Most index UTIs (79%) were caused by Escherichia coli, decreasing to 73% for the sixth UTI, while Klebsiella species rose from 7% of index UTIs to 11% for the sixth infection.

In total, 57% of index UTIs weren't susceptible to one or more antibiotic classes, and 13% of were resistant to at least three classes, climbing to 65% and 20%, respectively, by the sixth UTI. The most commonly resistant antibiotics were penicillins alone (12%) and a combination of penicillin, trimethoprim-sulfamethoxazole, and at least one more antibiotic class (9%).

Continuously updated data on susceptibility patterns are critical to guide appropriate antibiotic prescribing as well as to inform interventions to prevent repeated UTI events.

In the year before the index UTI, the most common antibiotic class prescribed for any reason were penicillins (16%), followed by first-generation cephalosporins (13%) and fluoroquinolones (5%). In the year before each subsequent UTI, first-generation cephalosporins and fluroquinolones were most common, followed by penicillins and nitrofurantoin.

"Continuously updated data on susceptibility patterns are critical to guide appropriate antibiotic prescribing as well as to inform interventions to prevent repeated UTI events," the authors wrote. 

"As the degree of resistance to the most frequently prescribed antibiotics for UTI evolves over time and may vary by region, it is also important to continuously monitor the local prevalence of uropathogens and their susceptibility to guide appropriate antibiotic use," they concluded. 

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