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2025 ; 25
(1
): 1391
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Haemophilus influenzae global epidemiology and antimicrobial susceptibility
patterns including ampicillin and amoxicillin-clavulanate resistance based on
?-lactamase production, 2013-2022
#MMPMID41131463
Sfeir MM
BMC Infect Dis
2025[Oct]; 25
(1
): 1391
PMID41131463
show ga
INTRODUCTION: The ?-lactam susceptibility of Haemophilus influenzae varies
globally due to resistance mechanisms such as ?-lactamase production or
alteration in Penicillin-Binding Protein 3 (PBP3). Monitoring and understanding
these resistance trends are crucial for guiding effective treatment strategies.
We described the global antimicrobial susceptibility patterns of H. influenzae
using the SENTRY Antimicrobial Surveillance Program, a large database designed to
monitor antimicrobial resistance patterns. METHODS: Antimicrobial susceptibility
testing was performed using broth microdilution as the reference method.
Demographics and phenotypic antimicrobial resistance of H. influenzae from over
150 medical centers representing 51 countries were analyzed between 2013 and
2022. The guidelines established by the Clinical and Laboratory Standards
Institute (CLSI) and the European Committee on Antimicrobial Susceptibility
Testing (EUCAST) were adopted to interpret antibiotic breakpoints. A nitrocefin
test was employed to assess the production of ?-lactamase. For statistical
analysis, we used Pearson?s Chi-square or Fisher?s exact test, considering
p???0.05 as significant. RESULTS: A total of 13,869 H. influenzae isolates were
analyzed; the majority came from the USA (52.2%) and the UK (4.3%). The most
affected groups were males under 18 years old and those over 65 years old.
?-lactamase was produced in 24.1% of the isolates, with significant variations in
antibiotic resistance across regions. Asia and the West Pacific exhibited the
highest resistance rates to ?-lactams and other antibiotics, including
?-lactamase-negative ampicillin-resistant (9.4%) and ?-lactamase-positive
amoxicillin-clavulanic acid-resistant (10.9%) isolates, while also having the
lowest rates of intensive care unit (ICU) admissions (14.9%) and invasive
infections (0.4% bloodstream infections and no central nervous system
infections). Ceftriaxone and piperacillin-tazobactam were the most in vitro
active antibiotics (100% susceptibility based on the CLSI breakpoints, 99.1% and
99.8% susceptibility, respectively, based on the EUCAST breakpoints). ?-lactamase
producing isolates had reduced susceptibility to amoxicillin-clavulanate (91.4%
vs. 95.4%), trimethoprim-sulfamethoxazole (61.2% vs. 66.5%), clarithromycin
(85.7% vs. 87.8%), azithromycin (97.1% vs. 98.9%), and tetracycline (95% vs.
99.6%) compared to ?-lactamase negative isolates. Contrarily, susceptibility to
fluoroquinolones was higher among ?-lactamase-producing isolates compared to
?-lactamase-negative isolates (99.6% vs. 94.1%, respectively). The in vitro
susceptibility of H. influenzae isolates was higher to azithromycin compared to
clarithromycin (98.4% vs. 87.2%), respectively. CONCLUSIONS: Reliance on the
nitrocefin test alone to predict susceptibility to ?-lactams, i.e., ampicillin,
could lead to false susceptibility and a higher chance of treatment failure. The
high prevalence of BLNAR and BLPACR in Asia and the West Pacific, along with
rising resistance to other antibiotics, highlights the need for reliable
diagnostic testing and stringent containment protocols. Empirical therapy with
clarithromycin for H. influenzae infections should be used with caution,
especially in high resistance settings.
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