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Journal of Chemotherapy
ISSN: 1120-009X (Print) 1973-9478 (Online) Journal homepage: https://www.tandfonline.com/loi/yjoc20
Surveillance of penicillin resistance of Neisseria
meningitidis
strains from invasive infections
between 2013 and 2018 in Turkey
Eda Karadag Oncel, Mehmet Ceyhan, Sevgen Tanir Basaranoglu, Venhar
Gurbuz, Ahmet Emre Aycan, Yasemin Ozsurekci, Zafer Kurugol, Melike
Keser Emiroglu, Ilker Devrim, Adem Karbuz, Havva Ozlem Altay Akisoglu &
Nezahat Gurler
To cite this article: Eda Karadag Oncel, Mehmet Ceyhan, Sevgen Tanir Basaranoglu, Venhar Gurbuz, Ahmet Emre Aycan, Yasemin Ozsurekci, Zafer Kurugol, Melike Keser Emiroglu, Ilker Devrim, Adem Karbuz, Havva Ozlem Altay Akisoglu & Nezahat Gurler (2020) Surveillance of penicillin resistance of Neisseria�meningitidis strains from invasive infections between 2013 and 2018 in Turkey, Journal of Chemotherapy, 32:4, 213-216, DOI: 10.1080/1120009X.2020.1721176
To link to this article: https://doi.org/10.1080/1120009X.2020.1721176
Published online: 07 Feb 2020.
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Surveillance of penicillin resistance of
Neisseria meningitidis strains from
invasive infections between 2013 and 2018
in Turkey
Eda Karadag Oncel
1, Mehmet Ceyhan
2, Sevgen Tanir Basaranoglu
2, Venhar
Gurbuz
2, Ahmet Emre Aycan
2, Yasemin Ozsurekci
2, Zafer Kurugol
3, Melike
Keser Emiroglu
4, Ilker Devrim
5, Adem Karbuz
6, Havva Ozlem Altay
Akisoglu
7, Nezahat Gurler
81
Clinics of Pediatric Infectious Diseases, SBU Izmir Tepecik Research and Training Hospital, _Izmir, Turkey;
2
Department of Pediatric Infectious Diseases, Hacettepe University School of Medicine, Ankara, Turkey;
3
Department of Pediatric Infectious Diseases, Ege University School of Medicine, Izmir, Turkey;4Department of Pediatric Infectious Diseases, Selc¸uk University Faculty of Medicine, Konya, Turkey;5Department of
Pediatric Infectious Diseases, Dr. Behc¸et Uz Children’s Hospital, Izmir, Turkey;6Clinics of Pediatric Infectious Diseases, Okmeydanı Training and Research Hospital, Istanbul, Turkey;7Department of Microbiology, Dr. Sami Ulus Maternity and Children’s Training and Research Hospital, Ankara, Turkey;
8
Department of Medical Microbiology, Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey
Neisseria meningitidis (N. meningitidis) is regarded as the leading cause of bacterial meningitis in many regions of the world. The empiric antimicrobial treatment is mainly based on antimicrobial resistance and patient characteristics. We aimed to analyze susceptibility patterns of N. meningitidis strains isolated in Turkey. Invasive meningococci collected in a multicenter, hospital-based, epidemiological surveillance study of pediatric (0–18 years of age) bacterial meningitis cases between 2013 and 2018 were studied. Five isolates (8.7%) displayed resistance to penicillin-G, while 13 isolates (22.8%) had intermediate susceptibility. All iso-lates were cefotaxime and rifampin susceptible. The data shows appropriateness of third-generation cephalo-sporins in empirical use for meningococcal infections in children. Since Turkey is located in a transition zone geographically, surveillance reports are very crucial.
Keywords: Neisseria meningitidis, antimicrobial susceptibility, surveillance, epidemiology, antimicrobial resistance, penicillin
Introduction
Neisseria meningitidis (N. meningitidis) is a
Gram-negative pathogen causing severe meningi-tis and septicemia, requiring prompt interventions
at the admission of pediatric patients. An
extended spectrum cephalosporin such as ceftriax-one is currently recommended for empirical
treat-ment of invasive meningococcal infections.1
Ceftriaxone, ciprofloxacin, and rifampin are
rec-ommended as chemoprophylactic agents.2 Active
surveillance of invasive meningococcal diseases is useful for determination of distribution of
sero-types and antimicrobial susceptibilities.
Serotyping helps in deciding immunization poli-cies, whereas antibiotic susceptibilities enable deci-sion making about empirical treatments, as well as chemoprophylaxis.
We primarily aimed to analyze antimicrobial susceptibilities of isolates from pediatric invasive meningococcal diseases, along with serotypes. Materials and methods
Invasive meningococci collected in a multicenter, hospital-based, epidemiological surveillance study of pediatric (0–18 years of age) bacterial meningitis cases in Turkey between 2013 and 2018 were studied. This epidemiological surveillance system consisted of 33 different hospitals in 7 geographical
regions of Turkey. Until antimicrobial
Corresponding author: Sevgen Tanir Basaranoglu, Department of Pediatric Infectious Diseases, Hacettepe University Faculty of Medicine, Sihhiye/Ankara, Turkey. Email:sevgent@gmail.com
susceptibility testing, disease causing isolates of N. meningitides cultured from blood and cerebrospinal
fluid were stored in 80C following collection
from centers. Then all of the isolates were cultured on sheep blood agars and incubated at 35–37C in
5% CO2 for 24 hours. After incubation, strains
were cultured on sheep blood agar plates and
re-incubated at 35–37C in 5% CO2 for 24 hours,
again. New colonies were collected and transferred to Mueller-Hinton broth, in order to adjust a sus-pension with a turbidity equivalent to that of 0.5 McFarland standard. Afterwards, few droplets were collected from the suspensions and inoculated
on 5% sheep blood Mueller Hinton broth.
Following partial absorption of suspension by the plate (in 10–15 minutes), E-test strips for penicillin G, cefotaxime and rifampin were placed on agar. Each and every strain were treated the same for each E-tests. Plates were incubated at 35–37C in
5% CO2 for 20–24 hours. After incubation,
min-imum inhibitory concentrations were calculated. The results of antimicrobial susceptibility tests were interpreted according to Clinical and Laboratory
Standards@Institute (CLSI-2014) recommendations3
(Table 1). Additionally, a sample of blood or CSF were also transported for phenotyping via polymer-ase chain reaction. The phenotypic determinations
of strains, based on the antigenic formula
(serogroup: serotype: serosubtype) of meningococcal isolates, were performed by standard methods in the Meningococcal Reference Unit, Health Protection Agency, Manchester, United Kingdom.4–6The study
was reviewed and approved by the local
Ethical Committee.
Statistical analyses were performed using IBM SPSS Statistics (Windows, Version 22.0. Armonk, NY: IBM Corp.). Descriptive statistics were used to summarize the participants’ baseline characteris-tics, including medians, interquartile ranges (IQR) for continuous and frequency distributions for cat-egorical variables.
Results
The study comprised of 57 patients with a median
age of 24 months (IQR: 7–72). Fifty-nine percent
(n¼ 34) of patients were male.
Five isolates (8.7%) displayed resistance to peni-cillin-G, while 13 isolates (22.8%) had intermediate susceptibility. All isolates were cefotaxime and rifampin susceptible. Overall, 38 (66.6%) strains were determined as serotype B, 11 (19.2%) as sero-type W, 4 (7%) as serosero-type A, 3 (5.2%) as serosero-type Y, and 1 (1.7%) as serotype X. Among the penicil-lin-G non- susceptible and intermediate susceptible
isolates, 55.5% (n¼ 10) were serogroup B; 27.7%
(n¼ 5) were serogroup W, and 11% (n ¼ 2) were
serogroup Y. All of the serogroup A isolates were
penicillin susceptible. Susceptibility pattern to
Penicillin G and serogroup distribution according to years were shown inTable 2.
Discussion
This was the first report of antibiotic susceptibility profile of N. meningitidis isolates obtained from pediatric meningitis surveillance data of Turkey. Penicillin non-susceptible and intermediate-suscep-tible isolates comprised 8.7% and 21% of the tested meningococci, respectively. None of the isolates were resistant to cefotaxime and rifampin. Since N. meningitidis is the leading cause of pediatric bacter-ial meningitis cases in Turkey after implementation of routine vaccination for Haemophilus influenzae type b and Streptococcus pneumoniae under 2 years
of age,7 empirical and targeted treatment options
of meningococcal meningitis became extremely important, in order to prevent deaths and sequelae. Antimicrobial treatment and chemoprophylaxis for patients with meningococcal disease and their close contacts is critical to reduce morbidity and mortal-ity and to prevent secondary cases.
Continuously changing epidemiology of the dis-ease requires surveillance of incidence, serogroup variations and antimicrobial susceptibility of men-ingococcal disease. Turkey is geographically located in a transition zone between Middle East, Asia and
Europe and is effected from both sides’
epidemi-ology. Epidemiology of meningitis belt of Africa also effects Turkey, because of the transmission of meningococcus by Hajj pilgrims from this area to
Saudi Arabia and to countries sending
pil-grims there.
Recently, a paper from Italy reported only 3 (27%) out of 11 strains that were fully susceptible to penicillin8 between 2013 and 2016. Before, until 2002, in the same region there were no penicillin resistant strains while only intermediate resistance were present (10%).9 Spain stated a similar penicil-lin resistance of meningococcal strains between 1986 and 1997. Of the 213 strains, 34% displayed reduced susceptibility and no resistant strains were detected.10
Later, between 1999 and 2006, in addition to reduced susceptibility to penicillin, ciprofloxacin
Table 1 MIC (lg/mL) interpretive breakpoints used for the antimicrobials tested in this study (CLSI 2014)
Susceptible Intermediate Resistant Penicillin G 0.06 0.12-0.25 0.5 Cefotaxime 0.12
Rifampin 0.5 1 2
E. K. Oncel et al. Surveillance of penicillin resistance of Neisseria meningitidis strains
resistance was reported from Spain.11 Recently, another data of rising resistance in meningococci came from France. Deghmane et al showed 2% of reduced susceptibility to third generation cephalo-sporins besides 26% of penicillin intermediate resistance. None of the isolates were resistant to
penicillin.12 Ten years of meningococcal
surveil-lance from Poland showed neither ciprofloxacin nor cephalosporin resistance, whereas 14.3% of iso-lates were intermediate susceptible and only 1.5% were resistant to penicillin.13 In a closer region to Turkey, Crotia, in a five year period, one isolate was ciprofloxacin resistant and 38.9% was inter-mediate susceptible to penicillin with no resistance to cephalosporins.14 In the present study, with no cephalosporin resistance and low non-susceptibility rates to penicillin, the data displayed the unique-ness of antibiotic susceptibility of meningococci in our country.
Invasive bacterial meningitis surveillance in
Turkey is mainly based on serogroup determination
by polymerase chain reaction. Therefore, the
serogroups in the present study did not reflect the whole pattern of serogroup distribution in our country. Between 2005 and 2012, the most preva-lent serogroup was W (38.1%), followed by B
(26.1%).7 During 2015–2016, the most common
serogroup was B (44.4%) and in 2017 most encoun-tered serogroup was W (65.2%) (unpublished data). Although there is a very rapidly changing epidemi-ology in the region, in the present report, it was important to note that non-susceptible and inter-mediate susceptible isolates were mostly from serogroup B. In Italy, four of the 8 penicillin
resist-ant isolates were serogroup B.8 In Poland,
serogroup B isolates were significantly more often nonsusceptible to penicillin than serogroup C (19% vs 11.3%). Among the ciprofloxacin resistant 10 isolates from Spain, 4 of them were serogroup B (11).On the other hand, between 2004 and 2011,
CDC reported penicillin nonsusceptibility in 19.5% of serogroup Y, whereas it was 7% serogroup B.15
The present study has some limitations, such as lack of follow-up evaluations, outcome data of patients, and further molecular studies of resistance genes. In addition, increased number of cultured meningococcus isolates would show the exact scene better. Still though, it is valuable showing the geo-graphical variations of meningococcal resistance in Turkey and the neighborhood.
Disclosure statement
The authors declare no conflict of interest.
Notes on contributors
Eda Karadag Oncel is an associate professor in
Pediatric Infectious Disease, Saglik Bilimleri
University, Izmir Tepecik Research and
Training Hospital.
Mehmet Ceyhan is a professor of Pediatric
Infectious Diseases in Hacettepe University
Medical School.
Sevgen Tanir Basaranoglu is a Pediatric Infectious
Disease specialist in Hacettepe University
Children’s Hospital.
Venhar Gurbuz is a medical biologist in Hacettepe
University Department of Pediatric
Infectious Diseases.
Ahmet Emre Aycan is a medical biologist in
Hacettepe University Department of Pediatric
Infectious Diseases.
Yasemin Ozsurekci is an associate professor of
Pediatric Infectious Diseases in Hacettepe
University Medical School.
Zafer Kurugol is a professor of Pediatric Infectious Diseases in Ege University Medical School.
Table 2 Susceptibility pattern to penicillin G and serogroup distribution according to years
2013 (n¼ 9) 2014 (n¼ 27) 2015 (n¼ 7) 2016 (n¼ 10) 2017 (n¼ 3) 2018 (n¼ 1) Total (n¼ 57) Penicillin G NS 1 4 0 0 0 0 5 (8.7) IS 1 4 4 2 1 0 12 (21) Serogroup A — 2 2 — — — 4 (7) Serogroup B 9 15 4 7 2 1 38 (66.6) NS 1 3 — — — — 4 (7) IS 1 1 3 1 — — 6 (10.5) Serogroup W — 8 1 1 1 — 11 (19.2) NS — 1 — — — — 1(1.7) IS — 2 1 — 1 — 4 (7) Serogroup Y 2 1 3 (5.2) IS 1 1 2 (3.5) Serogroup X 1 1 (1.7)
Melike Keser Emiroglu is an associate professor of
Pediatric Infectious Diseases in University
Medical School.
Ilker Devrim is a professor of Pediatric Infectious Diseases in Saglik Bilimleri University Izmir Dr Behcet Uz Children’s Hospital.
Adem Karbuz is an associate professor in Pediatric
Infectious Diseases in Istanbul Okmeydanı
Training and Research Hospital.
Havva Ozlem Altay Akisoglu is a Microbiology specialist in Ankara Dr Sami Ulus Maternity and Children’s Training and Research Hospital.
Nezahat Gurler is a professor of Microbiology in Istanbul University Medical School.
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E. K. Oncel et al. Surveillance of penicillin resistance of Neisseria meningitidis strains
