|Year : 2017 | Volume
| Issue : 1 | Page : 95-100
Prevalence of pneumococcal serotypes in adults ≥50 years of age
Chand Wattal1, Neeraj Goel1, SP Byotra2
1 Department of Clinical Microbiology and Immunology, Sir Ganga Ram Hospital, New Delhi, India
2 Department of Medicine, Sir Ganga Ram Hospital, New Delhi, India
|Date of Web Publication||16-Mar-2017|
Department of Clinical Microbiology and Immunology, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi - 110 060
Source of Support: None, Conflict of Interest: None
Context: Currently, majority of studies on antibiotic resistance and serotype prevalence in Streptococcus pneumoniae are in paediatric population and there is limited epidemiologic data pertaining to elderly Indian population. Aims: This study was undertaken to assess antibiotic resistance pattern and the coverage of the polysaccharide vaccine 23 (PPV23) in the elderly population. Settings and Design: This was a prospective 2-year pneumococcal surveillance study in patients with community-acquired pneumococcal infections of ≥50 years' age group on fifty isolates of S. pneumoniae. Materials and Methods: Antibiotic susceptibility by Kirby-Bauer disc diffusion method and minimum inhibitory concentration susceptibility testing by E-test method were performed for various antibiotics. All isolates were serotyped by the capsular Quellung method with commercial antisera. Results: All S. pneumoniae isolates were sensitive to penicillin and ceftriaxone. Non-susceptibility to levofloxacin, co-trimoxazole, erythromycin and clindamycin was noted as 16%, 74%, 10% and 6%, respectively. Prevalence of multidrug resistance in S. pneumoniae was observed as 6%. The most common serotypes observed in our study were 19A (14%), 8 (10%), 19F (8%), 3 (6%) and 9N (6%). PCV7, PCV10, PCV13 and PCV23 coverage was observed as 16%, 24%, 48% and 66%, respectively. The non-vaccine serotypes (NVTs) comprised 30% (n = 15) of the isolates. Conclusions: Our study shows different antibiotic susceptibility patterns of S. pneumoniae as compared to other neighbouring regions in Asia. The modest coverage of S. pneumoniae serotypes by PPV23 vaccine and prevalence of diverse NVTs in adult population make it a challenging task to recommend further changes in the future vaccine.
Keywords: Antimicrobial resistance, polysaccharide vaccine 23, Streptococcus pneumoniae, serotyping, vaccine
|How to cite this article:|
Wattal C, Goel N, Byotra S P. Prevalence of pneumococcal serotypes in adults ≥50 years of age. Indian J Med Microbiol 2017;35:95-100
|How to cite this URL:|
Wattal C, Goel N, Byotra S P. Prevalence of pneumococcal serotypes in adults ≥50 years of age. Indian J Med Microbiol [serial online] 2017 [cited 2017 Jun 25];35:95-100. Available from: http://www.ijmm.org/text.asp?2017/35/1/95/202332
| ~ Introduction|| |
Streptococcus pneumoniae is reported to be the most common cause of community-acquired pneumonia (CAP) and is estimated to cause approximately 30%–50% of CAP requiring hospitalisation in adults., Although the population aged <2 and ≥65 years have the highest rates of invasive pneumococcal disease (IPD) such as meningitis and bacteraemia, the highest mortality rates occur in individuals ≥65 years of age due to depleting immune mechanisms and associated co-morbid conditions.,,, Antimicrobial resistance (AMR) in S. pneumoniae further increases the mortality and morbidity associated with this infection., Penicillin had been the drug of choice for the treatment of pneumococcal infections, but now there are reports of high prevalence of penicillin-resistant pneumococci in certain regions of the world., Recent emergence of multidrug-resistant (MDR) S. pneumoniae is making its empirical treatment in outpatient settings difficult., Both incidence of IPD and AMR in S. pneumoniae has been linked to its serotype., Prevalence of various S. pneumoniae serotypes has shown to vary not only in different age groups and different geographic regions, but also with time in a given population exposed to antibiotics and pneumococcal vaccination.,, A polysaccharide vaccine containing 23 serotypes (PPV23) was introduced in 1980s to prevent pneumococcal disease in at-risk adults who have any of the several underlying medical conditions and to all persons >65 years of age.,, The protective value of PPV23 has been assessed to be 83%–63%. In addition, three pneumococcal conjugate vaccines (PCVs); PCV7, PCV10 and PCV13 are currently licensed for use in children. In addition, in 2014/2015, the US Advisory Committee on Immunization Practices (ACIPs) recommended routine use of PCV13 (Prevnar 13®) in series with PPV23 in all adults aged ≥65 years.,
As the efficacy of the vaccine is dependent on its coverage of the various serotypes in a given population, it is important to carry out periodic local surveillance studies to ascertain the different serotypes. Currently, the vast majority of studies on S. pneumoniae infections and serotypes have been reported in paediatric population and there is limited epidemiologic data pertaining to elderly Indian population. Therefore, this study was undertaken to assess the prevailing AMR and the serotype pattern in pneumococcal infections in adults ≥50 years of age.
| ~ Materials and Methods|| |
The study was conducted at a 675-bed, multi-speciality, tertiary care teaching hospital in New Delhi, India. This was a prospective 2-year pneumococcal surveillance study conducted between February 2013 and January 2015.
During this period, fifty consecutive S. pneumoniae isolates were collected from patients ≥50 years with pneumococal infections. The pneumococcal infection was categorised as IPD if S. pneumoniae was isolated from the sterile body sites such as blood, cerebrospinal fluid (CSF), pus, pleural fluids or any other sterile body fluids. S. pneumoniae isolates obtained from lower respiratory tract infections (sputum, endotracheal secretions and bronchial lavage/washings) from the patients with clinical and radiographic findings of pneumonia were included in the study only if the samples met the quality criteria of white blood cells ≥10 times the number of squamous epithelial cells per low-power field of microscopy accompanied by moderate-to-heavy predominant growth of S. pneumoniae in culture. Respiratory samples not meeting the above criteria were rejected and excluded from the study. Only the first isolate from each patient was included. Furthermore, any S. pneumoniae isolate obtained after 72 h of hospital admission was excluded from the study.
Identification and antimicrobial susceptibility testing
All the S. pneumoniae isolates were identified by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry, the VITEK MS system (BioMérieux, Marcy l'Etoile, France). Antimicrobial susceptibility testing (AST) was performed by Kirby-Bauer disc diffusion method as per the Clinical and Laboratory Standards Institute (CLSI) criteria for the following antibiotics: oxacillin, levofloxacin, co-trimoxazole, erythromycin, clindamycin and vancomycin. In addition, minimum inhibitory concentration (MIC) susceptibility testing system was performed using E-test (BioMérieux, Marcy l'Etoile, France) for the following antibiotics: penicillin, ceftriaxone, ciprofloxacin, co-trimoxazole and interpreted according to the CLSI standard. We also routinely performed the AST by automated VITEK II system (BioMérieux, Marcy l'Etoile, France) for diagnostic purposes but did not evaluate its result separately in this study as it was out of the purview of the present study.
All isolates were serotyped by the capsular Quellung method with commercial antisera (Statens Serum Institut, Copenhagen, Denmark) as per the manufacturer's guidelines.
The study was approved by the hospital's Institutional Review Board vide their letter number: EC/08/12/397.
| ~ Results|| |
A total of fifty patients of ≥50 years were recruited during the study period. The number of male patients was significantly higher than the female patients (male: 82% [n = 41], female: 18% [n = 9], P < 0.05). Maximum isolates were recovered from respiratory specimen (60%, n = 30), followed by blood (34%, n = 17), body fluids (2%, n = 1), pus (2%, n = 1) and corneal scrapings (2%, n = 1). The clinical presentation and predisposing factors for S. pneumoniae infection are shown in [Table 1] and [Table 2], respectively.
|Table 2: Predisposing factors for Streptococcus pneumoniae infection (n=50)|
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All S. pneumoniae isolates were sensitive to penicillin, ceftriaxone and vancomycin. Antimicrobial sensitivity to other drugs is shown in [Table 3] and [Figure 1]. Oxacillin disc diffusion testing showed 8% (n = 4) resistance, but all these isolates were sensitive to penicillin on MIC testing. Mean MIC, MIC range, MIC50 and MIC90 values of penicillin, ceftriaxone, levofloxacin and co-trimoxazole are depicted in [Table 4]. MDR in S. pneumoniae was defined as resistance to ≥3 classes of antibiotics  and was observed as 6% in our study.
|Table 3: Percentage antimicrobial sensitivity of Streptococcus pneumoniae|
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|Figure 1: Antibiotic susceptibility pattern of Streptococcus pneumoniae isolates (n = 50).|
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The most common serotype identified was 19A (14%), followed by 8 (10%), 19F (8%); 3 and 9N (6%) [Table 5] and [Figure 2]. PCV7, PCV10, PCV13 and PCV23 coverage was observed as 16%, 24%, 48% and 66%, respectively [Figure 3]. The non-vaccine serotype (NVT) comprised 30% (n = 15) of the isolates [Table 5] and [Figure 3]. The invasive serotypes comprised 38% (n = 19) of the total isolates in this study. These invasive isolates were as follows: 19A (15.8%), 1 (10.5%), 8 (10.5%), 3, 5, 13, 29, 31, 38, 10C, 24B, 47F, 7F, 9N and 9V (5.3% each). Interestingly, 36.8% (n = 7) of the invasive isolates were NVTs.
|Table 5: Serotypes of Streptococcus pneumoniae including nonvaccine serotypes (n=50)|
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|Figure 2: Percentage prevalence of various serotypes of Streptococcus pneumoniae.|
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|Figure 3: Streptococcus pneumoniae serotypes covered by various pneumococcal vaccines.|
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| ~ Discussion|| |
The present study describes the AMR pattern and serotype distribution of S. pneumoniae among adult population (≥50 years) from New Delhi, North India.
Antibiotic susceptibility testing
We did not find any penicillin non-susceptible pneumococci (PNSP) isolate in our study. Another study from South India between 2007 and 2011 also showed a low PNSP rate of 4.5%. Our findings are also consistent with the Asian Network for Surveillance of Resistant Pathogens study where India had the lowest rate (0%) of PNSP in the whole Asia. This study also showed an overall low prevalence rate of PNSP in Asian countries in non-meningeal isolates (mean: 4.6%, range: 0%–13.7%). Historically, there have been many reports of high prevalence of PNSP from across the world including Asia.,, The percentage of PNSP was reported as 33% in 1999–2000 in the USA. PNSP varied from 38.6% to 71.4% in Asia in 2000–2001. However, it is important to make a note that PNSP rates in non-meningitis clinical syndrome depend on whether the pre-2008 MIC (intermediate: 0.12–1.0 µg/ml; and resistant: ≥2.0 µg/ml) or 2008 MIC (intermediate: 4 µg/ml; and resistant: ≥8 µg/ml) breakpoints are used, thus limiting the comparability of the historic data and the recent data on PNSP. On analysis of penicillin MIC90, we observed its creep from 0.03 in 2000–2001 to 0.25 µg/ml in the current study. Similar penicillin MIC90 creep (1.0 µg/ml) has been seen in isolates from other parts of India in 2008–2009. We also did not report any resistance to ceftriaxone in S. pneumoniae, which is in agreement with the prevalence of low resistance to ceftriaxone (0%–4.4%) from other centres in India as well. As AMR has been shown to be associated with antibiotic consumption in S. pneumoniae, the low prevalence of its resistance to penicillin and ceftriaxone in India appears to be due to much lower use of penicillin group of antibiotics in comparison to macrolides or quinolones.,, Moreover, the availability of penicillin in Indian market is also limited.
We report a high prevalence of non-susceptibility to levofloxacin (16%) as compared to other Asian countries (2.4%) and the world (3.7%).,, Levofloxacin MIC90 in our study was 3 µg/ml (range: 0.25–32 µg/ml) as compared to 2 µg/ml (range: 1–2 µg/ml) in other Asian countries. Two of the isolates in our study showed very high MICs of 32 µg/ml. The high fluoroquinolone resistance observed in this study may limit the empirical use of fluoroquinolones in CAP in Indian settings. We showed a comparatively low prevalence of non-susceptibility to erythromycin (10%) and clindamycin (6%). Another study from South India also showed similar rates of macrolide resistance (13.6%). This is in contrast to a high macrolide resistance reported from the other Asian countries to erythromycin (72.7%), azithromycin (69.7%) and clarithromycin (68.9%). There is also an increase in resistance to macrolide in the Western hemisphere. A Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin (US) study reported an increasing trend in the macrolide non-susceptible S. pneumoniae, which increased significantly from 30.5% to 35.3% during 2005–2006 in 1 year (P < 0.0001). This increase in macrolide resistance is mainly seen in the serotypes 19A and 19F. In a study by Song et al., serotypes 19A and 19F showed a macrolide resistance of 86% and 79.8%, respectively. This high percentage of macrolide resistance in these two serotypes was due to the expansion of clonal complex (CC) 271. Our study also demonstrated 50% resistance to macrolide in serotype 19F, but in contrast, serotype 19A showed nil resistance to macrolide.
There was a high prevalence of resistance to co-trimoxazole (74%), which is comparable to other Indian reports of 68.9%–82% non-susceptibility to co-trimoxazole in S. pneumoniae., High level of non-susceptibility to co-trimoxazole in India can be due to the previous recommendation of use of this drug for the treatment of acute respiratory tract infection. Our study also showed a low rate of MDR (4%) which is in close agreement to 5.3% rate as reported by Molander et al., from India. In contrast, high MDR rates are seen in the Asian regions such as China (83.3%), Vietnam (75.5%), South Korea (63.9%), Hong Kong (62.2%) and Taiwan (59.7%) although lower rates of MDR in S. pneumoniae are seen in the Western world ranging from 0% to 43% in comparison to Asia.,,
The most common serotypes observed in our study were 19A (14%), 8 (10%), 19F (8%), 3 (6%) and 9N (6%). In a study by Shariff et al., from New Delhi between 2007 and 2010 on 126 S. pneumoniae isolates, a similar dominance of serotype 19 (26%) serogroup, followed by 6 (11%), 7 (10%), 1 (9%) and 14 (7%) was seen. This study did not further differentiate serogroup 19 into subtypes and had included patients from all age groups (2–77 years). Molander et al. from Vellore in their study on 138 S. pneumoniae isolates in adults (≥18 years of age) showed 1 (17.4%), 5 (11.6%), 6B (7.2%), 19F (5.1%) and 14 (2.2%) as the first five most common serotypes. Major serotypes of S. pneumoniae in the Asian region from elderly patients (≥65 years) in 541 patients were 19F (17%), 3 (12.4%), 23F (9.8%), 6B (7.9%), 14 (5.5%) and 19A (5.0%). In a report from Thailand, out of 172 isolates taken from patients ≥65 years between 2006 and 2009, the most common isolates were 6B, 19A, 23F, 4 and 9V. From the above data, it seems that there is a large dispersion in the prevalence of various serotypes from different parts of the world with predominance of 19A/19F serotypes. We have also seen the emergence of relatively hitherto uncommon serotypes such as 8, 3 and 9N. Serotype 19A is also being commonly reported as the predominant serotype associated with multidrug resistance. Serotype 19A constituted 20% of isolates in the USA and more than 30% were MDR.,,, In particular, a high prevalence of MDR in serotype 19A pneumococci has been observed in Hong Kong (100%), China (94.7%), Taiwan (90.9%) and South Korea (90.6%). Around 41% of 19A serotypes in the USA are also reported to be PNSP. In contrast, we did not report any MDR or PNSP in 19A serotype. The possible reason for this could be that the Indian isolates are of 1796 (2000, USA) and 4217 (1996, India) sequence types, which are not the same as MDR ST 320 types predominantly seen in Asian isolates., It has also been observed that the majority of the STs (78 of the 96 STs) circulating in India were unique sequences and only 4 STs were found in many countries with larger numbers.
Although the invasive potential of various serotypes varies, classically, serotypes 1, 4 5, 7F, 8 and more recently 19A are shown to be highly invasive serotypes. In our study, 19A (15.8%) was the most common invasive serotype. Invasive serotype 19A increased significantly in Spain from 4.6% during 1990–1999 to 13.5% during 2000–2008. 19A was also the most common invasive serotype (18.2%), reported from the USA from blood and CSF samples. The recent emergence of serotype 19A is also due to the expansion of the CC 320/271. As discussed above, ST320 serotype 19A isolates show a higher rate of antibiotic resistance compared to non-ST320 isolates and therefore antibiotic abuse/overuse might facilitate the spread of MDR serotype 19A strains.,,
In the present study, the observed coverage of PCV7, PCV10, PCV13 and PPV23 vaccines for S. pneumoniae serotypes was 16%, 24%, 48% and 66%, respectively. We could find only one study in India from Vellore assessing the coverage of pneumococcal vaccines in elderly (≥60 years) age group. The coverage of S. pneumoniae serotypes in this study for the PCV7, PCV10, PCV13 and PPV23 vaccines was 29%, 60% and 77% and 83%, respectively. In another multicentric study from Asian countries, the serotypes covered by PCV7, PCV10 and PCV13 in S. pneumoniae isolates from adults (65 years old) were 46.2%, 47.3% and 68.8%, respectively, but it did not assess the coverage for PPV23. In Europe, the coverage of PPV23 vaccine for S. pneumoniae serotypes from various countries ranged from 79.2% to 81%. PPV23 vaccine was introduced in 1983 with sero-coverage of 88% of IPD isolates from globally dispersed sites., However, the coverage of the PPV23 vaccine has declined to 60%–76% of IPD cases in 2009 in the USA. Specifically to IPD isolates, the PPV23 coverage in our study was even lower as 57.9%. In contrast, Thomas et al. from South India noted a higher PPV23 coverage of 82.3% in IPD serotypes of S. pneumoniae. With regard to the efficacy of PPV23 vaccine, a recent Cochrane meta-analysis of the randomised controlled trials found strong evidence of PPV 23 efficacy against IPD (odds ratio 0.26, 95% confidence interval 0.14–0.45) but could not demonstrate evidence in preventing pneumonia (of all causes) or mortality in adults. In fact, PCV13 has demonstrated efficacy in preventing vaccine-type pneumococcal CAP (45% efficacy) and vaccine-type IPD (75% efficacy) in adults aged ≥65 years in a CAPiTA study  due to its better immunogenicity profile for the vaccine serotypes in adults. Such efficacy studies are warranted from Indian region in light of modest coverage of pneumococcal vaccines on prevalent S. pneumoniae isolates.
Limitations and strengths of the study
As with most surveillance studies, this study had limitations. Only patients who had samples positive for culture for S. pneumoniae were included, and thus may not represent the general population. Furthermore, as our hospital is a tertiary care referral centre in North India, bias towards selection of patients with more severe clinical S. pneumoniae infections may have occurred and therefore may not reflect the true serotype prevalence in the Indian community. At the same time, the strength of our study is that there is a scarce data from India on the pneumococcal serotypes in the elderly age group. Most of the studies on S. pneumoniae serotypes are from paediatric age group. Even in studies from adults, most of the studies include patients of ≥17 years' age group, thus limiting the assessment of prevalent serotype coverage of S. pneumoniae PPV23 vaccine in the elderly population for whom they are primarily indicated.
| ~ Conclusions|| |
To conclude, our study shows very different AST pattern as compared to other neighbouring regions in Asia. We did not report any PNSP isolate but observed higher prevalence of resistance to quinolones and co-trimoxazole. The modest coverage of prevailing S. pneumoniae serotypes by PPV23 vaccine in the adult population and diverse prevalence of various NVTs make it a challenging task to recommend further changes in the future vaccine. Ongoing surveillance of antimicrobial susceptibility and serotype prevalence will be critical in formulating an evidence-based antibiotic policy and developing appropriate preventive strategies in elderly population for the region.
Financial support and sponsorship
This work was financially supported by Pfizer Limited., Pfizer Centre, 5, Patel Estate, Off. S.V. Road, Jogeshwari (W), Mumbai - 400102 (grant number: WS2392243).
Conflicts of interest
Sir Ganga Ram Hospital has received grant support from Pfizer Limited to carry out serotyping for this study. The design, result and manuscript preparation of the study were not influenced or supported by Pfizer Limited.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]