Antibiotic Susceptibility and Molecular Typing of Invasive Haemophilus influenzae Isolates, with Emergence of Ciprofloxacin Resistance, 2017–2021, Italy

Abstract

Haemophilus influenzae invasive disease is a severe infection that needs rapid antibiotic therapy. The aim of the study was to perform and evaluate the serotype distribution, antibiotic susceptibility and molecular characteristics of 392 H. influenzae invasive isolates collected during 2017–2021 in Italy. The majority of isolates were NTHi (305/392, 77.8%), followed by Hib (49/392, 12.5%). Ampicillin resistance was frequently detected (85/392, 21.7%): 12.2% were β-lactamase producers (all blaTEM except one blaROB), 9.4% were β-lactamase-negative ampicillin-resistant (BLNAR), with mutations in the ftsI gene. Six isolates were resistant to ciprofloxacin, with substitutions in GyrA and ParC. An MLST analysis revealed the occurrence of international resistant clones, such as ST103 and ST14, highlighting the importance of molecular surveillance.

National Danish surveillance of invasive clinical Haemophilus influenzae isolates and their resistance profile

“…Among the isolates tested, we detected genes encoding beta-lactamase enzymes in 12.5% of the isolates, with TEM-1B being the most frequently detected variant. This finding is consistent with previous studies demonstrating the predominance of TEM-type beta-lactamases in H. influenzae (Tønnessen et al, 2022;Giufrè et al, 2023).…”

“…Our findings revealed an overall beta-lactam resistance rate of 26.3% within the three classic distinct resistance mechanisms (gBLPAR, gBLNAR, and gBLPACR). These results are consistent with previous reports highlighting the widespread occurrence of these resistance mechanisms (Tønnessen et al, 2022;Giufrè et al, 2023). Notably, we observed a decrease in the frequency of gBLPAR isolates and an increase in gBLNAR isolates in 2020, coinciding with the first year of COVID-19.…”

“…Notably, the mutations V547I, N569S, and D350N were present in over 60% of BLNAS isolates. These mutations have previously been reported to confer resistance to beta-lactam antibiotics and contribute to the gBLNAR phenotype (Barbosa et al, 2011;Giufrè et al, 2023).…”

“…The emergence and spread of antibiotic resistance in H. influenzae strains present a notable challenge in effectively addressing invasive infections (Tønnessen et al, 2022;Giufrè et al, 2023). This study aimed to analyze the molecular characteristics of various antimicrobial resistance traits among the collected H. influenzae isolates.…”

“…Molecular analysis of beta-lactam resistance was done by blasting for beta-lactamase gene 6 and if positive was termed genetic betalactamase-positive ampicillin-resistant (gBLPAS). Moreover, they were further analyzed and characterized by PBP3 substitutions (PBP group; Skaare et al, 2014) including ftsI allele typing (Giufrè et al, 2023).…”