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Observational Study
. 2019 Dec 11;19(1):1049.
doi: 10.1186/s12879-019-4675-y.

First-line antibiotic susceptibility pattern of toxigenic Corynebacterium diphtheriae in Indonesia

Dominicus Husada  1 , Sugi Deny Pranoto Soegianto  2 , Indra Suwarin Kurniawati  3 , Adi Pramono Hendrata  3 , Eveline Irawan  3 , Leny Kartina  2 , Dwiyanti Puspitasari  2 , Parwati Setiono Basuki  2 , Ismoedijanto  2
Affiliations
Observational Study

First-line antibiotic susceptibility pattern of toxigenic Corynebacterium diphtheriae in Indonesia

Dominicus Husada et al. BMC Infect Dis. .

Abstract

Background: Diphtheria has been reported as an outbreak in some regions in Indonesia, most especially in East Java Province. Resistance to penicillin, erythromycin, and other antibiotics, single or multiple, has been reported in several studies. This study aims to evaluate the first-line antibiotic susceptibility pattern of toxigenic Corynebacterium diphtheriae isolates.

Methods: This descriptive observational study was performed from August to November 2018. C. diphtheriae isolates were collected from diphtheria patients and carriers in East Java from 2012 to 2017 and kept at the Balai Besar Laboratorium Kesehatan Daerah Surabaya or the Public Health Laboratory of Surabaya. Sample selection was done by random cluster sampling. The sensitivity test by E-test®of the five antibiotics (penicillin, oxacillin, erythromycin, azithromycin, and clarithromycin) was done to determine the minimum inhibitory concentration (MIC). The Clinical and Laboratory Standards Institute M45A (2015) Corynebacterium spp. for penicillin and erythromycin was used as standard.

Results: From 114 targeted isolates, 108 were viable and toxigenic. The E-test was performed on the viable isolates. The majority of the hosts were male (58.3%), with median (range) age of 6.5 (1-14) years. Half of the samples were from the 1 to 5-year-old age group. The isolates were acquired much more from patients (78.7%) than carriers (21.3%) and from pharyngeal swab (74.1%). Most of these isolates were from Madura Island (47.2%) and the northern and eastern parts of the province (horseshoe area). Mitis isolates were the major variant (76.9%). The susceptibility pattern of C. diphtheriae to erythromycin was better than that to penicillin. The E-test result for penicillin was 68.52% susceptible, 31.48% intermediate, and 0% resistant (MIC range, < 0.016 to 2 μg/L) and for erythromycin (MIC range, < 0.016 to > 256 μg/L) was 85.2% susceptible, 12% intermediate, and 2.8% resistant The MIC range for oxacillin was 1 to 96 μg/L, while for both azithromycin and clarithromycin were < 0.016 to > 256 μg/L.

Conclusion: The susceptibility rate of C. diphtheriae to erythromycin is higher than that to penicillin. The regular update of antibiotic selection to the national guidelines is recommended. The MIC reference standard to azithromycin and clarithromycin is also needed.

Keywords: Corynebacterium diphtheriae; Erythromycin; First line antibiotics; Indonesia; Penicillin; Susceptibility pattern; Toxigenic.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
MIC of the five antibiotics. a Penicillin; b erythromycin; c oxacillin; d clarithromycin; e azithromycin Vertical axis: Number of isolates Horizontal axis: MIC (μg/L) Biotypes: mitis (red); gravis (blue)
Fig. 2
Fig. 2
Comparison of MIC of the three macrolides, focusing on less susceptible isolates to erythromycin a Resistant isolates to erythromycin (3 isolates). b Intermediate isolates to erythromycin (13 isolates) Vertical axis: MIC (μg/L); In Fig. 2b, the MIC of azithromycin was one tenth of the real value Horizontal axis: code number of isolates Color: erythromycin/EM (red), clarithromycin/CH (yellow), azithromycin/AZ (green)
See this image and copyright information in PMC

References

    1. Hughes GJ, Mikhail AF, Husada D, Irawan E, Kafatos G, Bracebridge S, Pebody R, Efstratiou A. Seroprevalence and determinants of immunity to diphtheria for children living in two districts of contrasting incidence during an outbreak in East Java, Indonesia. Pediatr Infect Dis J. 2015;34(11):1152–1156. doi: 10.1097/INF.0000000000000846. - DOI - PubMed
    1. Husada D, Puspitasari D, Kartina L, Basuki PS, Moedjito I, Kartiko BW. Six-year surveillance of diphtheria outbreak in Indonesia. Open Forum Infect Dis. 2017;4(Suppl 1):S224.
    1. Pereira GA, Pimenta FP, Dos Santos FRW, Damasco PV, Junior RH, Mattos-Guaraldi AL. Antimicrobial resistance among Brazilian Corynebacterium diphtheriae strains. Mem Inst Oswaldo Cruz. 2008;103:507–510. doi: 10.1590/S0074-02762008000500019. - DOI - PubMed
    1. Engler KH, Warner M, George RC. In vitro activity of ketolides HMR 3004 and HMR 3647 and seven other antimicrobial agents against Corynebacterium diphtheriae. J Antimicrob Chemother. 2001;47:27–31. doi: 10.1093/jac/47.1.27. - DOI - PubMed
    1. Kneen R, Pham NG, Solomon T, Tran TM, Nguyen TT, Tran BL, Wain J, Day NP, Tran TH, Parry CM, White NJ. Penicillin vs. erythromycin in the treatment of diphtheria. Clin Infect Dis. 1998;27:845–850. doi: 10.1086/514959. - DOI - PubMed

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