Extensively drug-resistant Haemophilus influenzae - emergence, epidemiology, risk factors, and regimen

Abstract

Background: Concern about Haemophilus influenzae infection has been increasing over recent decades. Given the emergence of H. influenzae with severe drug resistance, we assessed the prevalence of as well as risk factors and potential therapies for extensively drug-resistant (XDR) H. influenzae infection in Taiwan.

Results: In total, 2091 H. influenzae isolates with disk diffusion-based antibiotic susceptibility testing from 2007 to 2018 were enrolled. H. influenzae strains resistant to ampicillin, chloramphenicol, levofloxacin, and trimethoprim-sulfamethoxazole tended to be isolated from patient wards (≧41%), whereas those resistant to amoxicillin-clavulanate, cefotaxime, and cefuroxime were more likely to be isolated from intensive care units (approximately 50%). XDR H. influenzae was first identified in 2007, and its incidence did not significantly change thereafter. Overall prevalence of single, multiple, and extensively drug-resistant H. influenzae over 2007-2018 was 21.5% (n = 450), 26.6% (n = 557), and 2.5% (n = 52), respectively. A stepwise logistic regression analysis revealed that blood culture (odds ratio: 4.069, 95% confidence intervals: 1.339-12.365, P = 0.013) was an independent risk factor for XDR H. influenzae infection. No nosocomial transmission of XDR H. influenzae observed. Antibiotic susceptibility testing results demonstrated that cefotaxime was effective against 78.8% (n = 41) of the XDR strains.

Conclusions: The presence of XDR H. influenzae strains was identified in Taiwan, and cefotaxime was efficacious against most of these strains.

Keywords: Antimicrobial susceptibility testing; Cefotaxime; Drug resistance; Haemophilus influenzae.

Fig. 1

Drug non-susceptibility in Haemophilus influenzae. a Incidences of drug non-susceptibility to different antimicrobial agents in H. influenzae isolates from 2007 to 2018 (n = 2091) are shown. Fisher’s exact tests or Pearson Chi-square tests were used to assess the significance of the non-susceptible rate of each drug in each year when compared to the overall mean value. *P <  0.05, **P <  0.01, ***P <  0.001. x̄, mean value. b Comparisons of drug non-susceptibility rates in β-lactamase-positive and β-lactamase-negative H. influenzae isolates. P-values are obtained from Fisher’s exact tests

Fig. 2

Drug non-susceptibility of Haemophilus influenzae from different origins. a Percentages of drug non-susceptible H. influenzae in specimens from different departments are shown. b Comparisons of drug non-susceptibility rates in hospitalized patients between respiratory care wards/center (n = 313) and other units (n = 1106) are shown in column graphs. P-values are obtained from Chi-square tests

Fig. 3

Drug resistant status of Haemophilus influenzae. (a) Trends of different H. influenzae drug resistant status from 2007 to 2018 are shown. (b) β-lactamase-positive rates in MDR, non-MDR, XDR, and non-XDR H. influenzae isolates are shown. The number of each group is shown in the bar. P-values are obtained from Pearson Chi-square tests. Proportions of different drug resistant status under (c) different specimen types and (d) different specimen sources are shown. Pearson Chi-square tests were used to assess the significance of each analysis. MDR, multiple drug-resistance; NR, no resistance; SDR, single drug-resistance; TDR, two drug-resistance; x̄, mean value; XDR, extensive drug-resistance