Indian Journal of Medical Microbiology IAMM  | About us |  Subscription |  e-Alerts  | Feedback |  Login   
  Print this page Email this page   Small font sizeDefault font sizeIncrease font size
 Home | Ahead of Print | Current Issue | Archives | Search | Instructions  
Users Online: 1765 Official Publication of Indian Association of Medical Microbiologists 
 ~  Similar in PUBMED
 ~  Search Pubmed for
 ~  Search in Google Scholar for
 ~Related articles
 ~  Article in PDF (461 KB)
 ~  Citation Manager
 ~  Access Statistics
 ~  Reader Comments
 ~  Email Alert *
 ~  Add to My List *
* Registration required (free)  

 ~  Abstract
 ~ Introduction
 ~  Materials And Me...
 ~ Results
 ~ Discussion
 ~ Conclusions
 ~  References
 ~  Article Figures
 ~  Article Tables

 Article Access Statistics
    PDF Downloaded411    
    Comments [Add]    

Recommend this journal


  Table of Contents  
Year : 2017  |  Volume : 35  |  Issue : 2  |  Page : 228-236

Increasing incidence of penicillin- and cefotaxime-resistant Streptococcus pneumoniae causing meningitis in India: Time for revision of treatment guidelines?

1 Department of Paediatrics, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
2 Department of Clinical Microbiology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
3 National Institute of Epidemiology, ICMR, Chennai, Tamil Nadu, India
4 Department of General Medicine, Christian Medical College and Hospital, Vellore, Tamil Nadu, India

Date of Web Publication5-Jul-2017

Correspondence Address:
Valsan Philip Verghese
Department of Paediatrics, Christian Medical College and Hospital, Vellore, Tamil Nadu
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijmm.IJMM_17_124

Rights and Permissions

 ~ Abstract 

Purpose: Pneumococcal meningitis is a life-threatening infection, requiring prompt diagnosis and effective treatment. Penicillin resistance in pneumococcal infections is a concern. Here, we present the antibiotic susceptibility profile of pneumococcal meningeal isolates from January 2008 to August 2016 to elucidate treatment guidelines for pneumococcal meningitis. Materials and Methods: Invasive pneumococcal isolates from all age groups, were included in this study. Minimum inhibitory concentrations for the isolates were identified by agar dilution technique and VITEK System 2. Serotyping of isolates was done by co-agglutination technique. Results: Out of 830 invasive pneumococcal isolates, 167 (20.1%) isolates were from meningeal infections. Cumulative penicillin resistance in pneumococcal meningitis was 43.7% and cefotaxime non-susceptibility was 14.9%. Penicillin resistance amongst meningeal isolates in those younger than 5 years, 5–16 years of age and those aged 16 years and older was 59.7%, 50% and 27.3%, respectively, with non-susceptibility to cefotaxime in the same age groups being 18%, 22.2% and 10.4%. Penicillin resistance amongst pneumococcal meningeal isolates increased from 9.5% in 2008 to 42.8% in 2016, whereas cefotaxime non-susceptibility increased from 4.7% in 2008 to 28.5% in 2016. Serotypes 14, 19F, 6B, 6A, 23F, 9V and 5 were the most common serotypes causing meningitis, with the first five accounting for over 75% of resistant isolates. Conclusions: The present study reports increasing penicillin resistance and cefotaxime non-susceptibility to pneumococcal meningitis in our setting. This highlights the need for empiric therapy with third-generation cephalosporins and vancomycin for all patients with meningitis while awaiting results of culture and susceptibility testing.

Keywords: Cefotaxime non-susceptible, combination therapy, India, penicillin resistance, pneumococcal meningitis

How to cite this article:
Verghese VP, Veeraraghavan B, Jayaraman R, Varghese R, Neeravi A, Jayaraman Y, Thomas K, Mehendale SM. Increasing incidence of penicillin- and cefotaxime-resistant Streptococcus pneumoniae causing meningitis in India: Time for revision of treatment guidelines?. Indian J Med Microbiol 2017;35:228-36

How to cite this URL:
Verghese VP, Veeraraghavan B, Jayaraman R, Varghese R, Neeravi A, Jayaraman Y, Thomas K, Mehendale SM. Increasing incidence of penicillin- and cefotaxime-resistant Streptococcus pneumoniae causing meningitis in India: Time for revision of treatment guidelines?. Indian J Med Microbiol [serial online] 2017 [cited 2020 Oct 23];35:228-36. Available from:

 ~ Introduction Top

Pneumococcal meningitis is lethal even in optimal therapeutic settings, with a case fatality rate close to 30%[1],[2] and long-term neurological sequelae in a significant proportion of survivors.[2],[3] The burden of disease is also high in resource-poor developing countries like India,[4] indicating the need for strategies to prevent disease and to formulate effective treatment guidelines.

Penicillin was the standard drug of choice for treating pneumococcal infections for many years until increasing global resistance to penicillin [5],[6] necessitated the use of alternative antibiotics. Penicillin susceptibility break points for Streptococcus pneumoniae of <0.06 μg/mL, 0.12–1 μg/mL and >2 μg/mL for susceptibility, intermediate susceptibility and resistance, respectively, were derived by the Clinical and Laboratory Standards Institute (CLSI) in the 1970s and followed till 2007. These guidelines, meant to ensure success in treating pneumococcal meningeal infections, were adapted for all pneumococcal infections.[7] However, large observational studies documenting the clinical success of parenteral penicillin therapy in patients with penicillin non-susceptible pneumococcal pneumonia and bacteraemia showed that break points formulated for successful treatment of pneumococcal meningeal infections may not be applicable to non-meningeal infections.[8],[9],[10] This resulted in the introduction by the CLSI in January 2008 of two separate susceptibility break points for pneumococcal meningeal and non-meningeal infections.[11] The new susceptibility break point changes were derived based on reviews on microbiological, pharmacokinetics and/or pharmacodynamics and clinical outcome data.[7] The revised 2008 CLSI break point changes for penicillin are represented in [Table 1]. Cefotaxime minimum inhibitory concentration (MIC) break points defining susceptibility, intermediate susceptibility and resistance published by CLSI are ≤0.5, 1.0 and ≥2 μg/mL, respectively, for meningeal infections from 1994[12] and ≤1.0, 2.0 and ≥4 μg/mL for non-meningeal infections from 2002.[7]
Table 1: Comparison of earlier and revised Clinical and Laboratory Standards Institute susceptibility break points for penicillin for treating pneumococcal infections

Click here to view

The revised CLSI susceptibility break points for penicillin in 2008 resulted in decreased penicillin non-susceptibility amongst non-meningeal pneumococcal isolates reported before 2008 due to the increase in non-susceptibility cut-offs to 4 μg/mL. Although the number of penicillin non-susceptible meningeal isolates remained unchanged, the number of isolates classified as resistant increased as those previously classified as having intermediate susceptibility with MIC 0.12–1 μg/mL were now re-categorised as resistant (MIC ≥0.12 μg/mL) under the 2008 break points.[13],[14] Despite these changes, non-susceptibility to penicillin and cefotaxime continues to increase over time amongst both meningeal and non-meningeal pneumococcal infections [15],[16] indicating the need for ever-evolving strategies for effective treatment guidelines.

In this study, we identify the pattern of antibiotic susceptibility in invasive pneumococcal infections over a period of 8 years and 8 months, with special emphasis on resistance to penicillin and non-susceptibility to third-generation cephalosporins in pneumococcal isolates causing meningitis, and review existing treatment guidelines for pneumococcal meningitis.

 ~ Materials And Methods Top

This laboratory-based prospective study was conducted at Christian Medical College Hospital, a tertiary care hospital in South India, from January 2008 to August 2016. Invasive pneumococcal isolates from blood, cerebrospinal fluid (CSF) and sterile body fluids in all age groups from our hospital as part of invasive bacterial disease surveillance and those from other sentinel sites as a part of reference laboratory activity for hospital-based sentinel surveillance of bacterial meningitis were included in this study. Pneumococcal isolation and confirmation were based on standard laboratory protocols.[17] MIC testing of isolates was done by agar dilution [18] from 2008 to 2010 and with VITEK System 2 (BioMerieux, France) from 2011 to 2016. Antimicrobial susceptibility testing interpretations were based on CLSI guidelines 2016.[19] Serotyping of isolates was done by co-agglutination technique [20] with Neufeld antisera obtained from Statens Serum Institut, Denmark.

Case definitions

Pneumococcal meningeal infection was defined as isolation of S. pneumoniae from CSF or blood in a patient with a clinical syndrome consistent with meningitis: CSF leucocytosis >100 cells/mm 3 or 10–100 cells/mm 3 with either an elevated CSF protein (>100 mg/dL) or decreased CSF glucose (<40 mg/dl).[21] Pneumococcal non-meningeal infection was defined as isolation of S. pneumoniae from blood or sterile body fluids from a patient without a meningitis clinical syndrome.[22]

 ~ Results Top

A total of 830 invasive pneumococcal isolates were investigated in this study, of which 37.5% (311) of the isolates were in children aged <5 years, 12.8% (106) in children aged 5–16 years and 49.7% (413) of the isolates were from those 16 years of age and older. 20.1% (167) of the isolates were from meningeal infection, whereas 79.9% (663) of the isolates were from non-meningeal infections.

Of the 167 isolates causing meningitis in our study group, 43.7% (73) and 14.9% (25) were non-susceptible to penicillin and cefotaxime, respectively [Table 2], with all isolates non-susceptible to cefotaxime being non-susceptible to penicillin as well. Amongst the 25 meningeal isolates non-susceptible to cefotaxime, 17 isolates had intermediate susceptibility, whereas 8 isolates were fully resistant to cefotaxime. Non-susceptibility to erythromycin and co-trimoxazole was found in 37.1% (62) and 97% (162) respectively. Non-susceptibility to erythromycin along with penicillin was noted in 29.9% (50) of isolates causing meningitis. Multidrug resistance (non-susceptibility to penicillin, cefotaxime and erythromycin) was found in 12.3% (20) of study isolates causing pneumococcal meningitis.
Table 2: Penicillin resistance and cefotaxime non-susceptibility in invasive pneumococcal isolates, January 2008 - August 2016

Click here to view

Amongst pneumococcal isolates causing meningitis in <5 year, 5–16 year and ≥16 year age groups, 59.7% (43), 50% (9) and 27.3% (21), respectively, were non-susceptible to penicillin. Cefotaxime non-susceptibility amongst meningeal isolates was 18% (13), 22.2% (4) and 10.4% (8) in 0–5 years, 5–16 year and ≥16 year age groups, with nine, three and five isolates, respectively, having intermediate susceptibility to cefotaxime while four, one and three isolates were fully resistant amongst each of the age groups. Amongst non-meningeal isolates, non-susceptibility to penicillin was seen in four isolates (0.60%). Three of these isolates were from children younger than 5 years, with one isolate being fully resistant and the other two having intermediate susceptibility to penicillin. Only one isolate from a subject older than 16 years had intermediate susceptibility to penicillin. Overall, penicillin non-susceptibility was 9.3% from all invasive pneumococcal disease (IPD) isolates [Table 2].

Over the study period, penicillin resistance amongst pneumococcal meningeal isolates increased from 9.5% in 2008 to 42.8% in 2016, whereas cefotaxime non-susceptibility increased from 4.7% in 2008 to 28.5% in 2016 [Figure 1].
Figure 1: Trend analysis of penicillin and cefotaxime non-susceptibility in pneumococcal meningeal isolates, January 2008 – August 2016.

Click here to view

Serotypes 14 (22 isolates), 19F (17 isolates), 6B (13 isolates), 6A (11 isolates), 23F, 9V and 5 (7 isolates each) were the predominant serotypes causing pneumococcal meningitis, making up 50.3% of all meningeal serotypes [Table 3]. Serotypes 14, 19F, 6B, 5 and 9V were predominant in pneumococcal meningeal isolates in children <5 years of age. 19F and 6A predominated in those aged 5–16 years and were also found in meningeal isolates from those older than 16 years, along with serotypes 3, 1, 6B, 15A and 13 [Figure 2].
Table 3: Serotype distribution and penicillin resistance in pneumococcal meningeal isolates (n=167)

Click here to view
Figure 2: Serotype distribution of isolates of Streptococcus pneumoniae causing meningitis, by age group.

Click here to view

In this study, serotypes 14 (19 isolates), 6A and 19F (11 isolates each), 6B (10 isolates) and 23F (5 isolates) were the predominant serotypes in penicillin-resistant pneumococcal meningitis, making up 76.7% of all resistant isolates [Table 3]. 58.9% of penicillin-resistant meningeal isolates were from children younger than 5 years. Serotypes 14, 19F and 6B were the most common causes of penicillin-resistant pneumococcal meningitis in children <5 years of age, whereas serotypes 6A, 19F, 23F, 6B and 19V predominated in those older than 5 years [Figure 3].
Figure 3: Serotype distribution of penicillin-resistant isolates of Streptococcus pneumoniae causing meningitis.

Click here to view

 ~ Discussion Top

Although the overall prevalence of non-susceptibility to penicillin in IPD during the study period remains low at 9.3%, increasing penicillin resistance of pneumococcal meningeal isolates, from <10% in 2008 to over 40% by 2016, mirrors the rise in resistance to penicillin documented worldwide [Table 4].[2],[14],[15],[16],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39],[40],[41],[42],[43],[44],[45] The range of documented global penicillin resistance after 2008 ranges from 20% to 30% in Brazil and Argentina through 40% in the USA to over 50% in Asia and Africa, with rates approaching or above 80% in Taiwan and China. Although factors such as the injudicious use of antibiotics could account for this increase in developing countries, international dissemination of penicillin-resistant clones such as ST 63 (Sweden 15A-25), already documented from our institution,[46] could also contribute to rising penicillin resistance in our country.
Table 4: Penicillin and cefotaxime non-susceptibility of invasive pneumococcal infections in other parts of the world

Click here to view

Increasing non-susceptibility to cefotaxime amongst meningeal isolates, from <5% in 2008 to over 25% in 2016 parallels the rise in penicillin resistance, with most studies documenting that cefotaxime non-susceptibility is predominantly seen amongst penicillin non-susceptible isolates.[6],[7] Although cefotaxime non-susceptibility is less well characterised amongst global surveillance studies, our figures are close to the over 30% cefotaxime non-susceptibility documented from Asia and Africa.[33],[37]

While different penicillin susceptibility break points were formulated for meningeal and non-meningeal pneumococcal isolates based on documentation of clinical cure in non-meningeal pneumococcal infections such as pneumonia,[8],[10] there are fewer studies on outcomes in pneumococcal meningitis. Cefotaxime has been proved to be efficacious in treating patients with pneumococcal meningitis with isolates resistant to penicillin but susceptible to cefotaxime.[12] Conversely, treatment of pneumococcal meningitis with cefotaxime or ceftriaxone to which the isolates were intermediately resistant has been associated with treatment failure.[47],[48] Case fatality rates are usually higher with pneumococcal meningitis compared to non-meningeal infections, especially in those with non-susceptible infections.[49] From 1995 to 2005 at a public hospital in Brazil, the case fatality rate was 37% in children with pneumococcal meningitis, of whom 17% were penicillin resistant. Mortality was significantly higher amongst children <15 years of age with penicillin resistance, which was also associated with a higher case fatality rate even when the initial treatment regimen included ceftriaxone. The case fatality rate was higher amongst those who did not receive an antibiotic to which the isolate was susceptible during the first 24 h of therapy.[2] Amongst survivors assessed before discharge, 36% were documented to have a neurological deficit, similar to the 40% incidence of sequelae from another Brazilian study.[24] Child survivors of pneumococcal meningitis in Bangladesh showed evidence of hearing, visual, mental, or psychomotor delay, with ≥1 type of impairment in 65% of children on short-term follow-up and in 49% on long-term follow-up after 6–24 months.[3]

The high mortality and morbidity associated with pneumococcal meningitis has led to most recent antibiotic treatment guidelines for pneumococcal meningitis recommending the use of vancomycin along with cefotaxime or ceftriaxone to treat pneumococcal meningitis where the isolate is non-susceptible to both penicillin and cefotaxime [Table 5].[50],[51],[52],[53],[54] The Indian Council of Medical Research's recently released guidelines on antimicrobial use in common syndromes [55] recommends the use of ceftriaxone with ampicillin (without vancomycin) in the treatment of acute bacterial meningitis due to the low level of penicillin resistance in pneumococcal infections. Our study is one of the first in the country to document penicillin non-susceptibility in meningeal versus non-meningeal isolates in IPD. The high level of penicillin resistance in our pneumococcal meningeal isolates leads us to believe that it would be prudent to add vancomycin to ceftriaxone for initial treatment of acute bacterial meningitis till culture reports become available, after which antibiotics can be administered based on results of susceptibility testing. Non-susceptibility to penicillin in non-meningeal pneumococcal isolates in our study being <1%, penicillin (or ceftriaxone) would continue to be appropriate therapy for such infections.
Table 5: Various antibiotic guidelines for pneumococcal meningitis in children and adults

Click here to view

The most common serotypes 14, 19F, 6B, 6A, 9V, 23F and 5 documented in this study were the same as those documented to be the most prevalent globally.[37],[56] Non-susceptibility to penicillin was predominantly seen with the first six of the above-mentioned serotypes, similar to studies elsewhere.[31],[57] Serotypes 1 (associated with meningitis outbreaks in Africa), 3 and 15A were the next most commonly isolated serotypes. Serotype 3, commonly found in meningitis in infants and children below the age of 2 in Brazil,[25] was only isolated from those older than 16 years in our study. The 13-valent pneumococcal conjugate vaccine (PCV-13), already available in India from private healthcare providers, would cover 86% of penicillin-resistant isolates in those <5 years of age, and 80% of resistant isolates in those aged 5 years and older [Figure 3]. This is similar to other surveillance studies that predict over 80% coverage of IPD serotypes by PCV-13.[32],[37],[42] Serotype 19A, a significant cause of penicillin-resistant IPD after introduction of PCV-7,[58],[59] was only seen in 2 isolates, both resistant, that would also be covered by PCV-13.

A limitation of our study was the use of two different methods for testing susceptibility, the agar dilution method for 198 isolates from 2008 to 2010 and since VITEK system 2 (an automated system with lesser turnaround time) was available from 2011, the VITEK system 2 to ascertain MIC for 632 isolates from 2011 to 2016. Studies comparing VITEK system with reference methods for identifying penicillin MIC for S. pneumoniae have shown excellent essential agreement with 91.8%–95% and categorical agreement with 94.2%–96%.[60],[61] To validate our findings with VITEK system 2, 33 isolates that were penicillin non-susceptible to S. pneumoniae by VITEK system 2 were rechecked with E-test, and we obtained 100% concordance. With the E-test also having excellent essential agreement and categorical agreement with 95%–96% and 93%–97%, respectively,[60],[61] we feel that this is unlikely to have affected the validity of our results.

 ~ Conclusions Top

Our study documents the presence of significant increase in penicillin resistance and cefotaxime non-susceptibility in pneumococcal meningitis in India. This emphasises the need to use combination therapy with vancomycin added to cefotaxime or ceftriaxone for all patients with pneumococcal meningitis until the treatment regimen can be modified using results of susceptibility testing. Penicillin is still a reliable drug for non-meningeal pneumococcal infections. The results from this study can be used to formulate treatment guidelines for pneumococcal meningitis in other parts of the country as well.


Our sincere thanks to the Centers for Disease Control and Prevention, Atlanta, USA for providing laboratory training to conduct pneumococcal surveillance in India.

Financial support and sponsorship

The World Health Organization, Geneva, and Ministry of Health and Family Welfare, for their financial support to conduct pneumococcal surveillance activities in India.

Conflicts of interest

There are no conflicts of interest.

 ~ References Top

Weisfelt M, van de Beek D, Spanjaard L, Reitsma JB, de Gans J. Clinical features, complications, and outcome in adults with pneumococcal meningitis: A prospective case series. Lancet Neurol 2006;5:123-9.  Back to cited text no. 1
Gouveia EL, Reis JN, Flannery B, Cordeiro SM, Lima JB, Pinheiro RM, et al. Clinical outcome of pneumococcal meningitis during the emergence of pencillin-resistant Streptococcus pneumoniae: An observational study. BMC Infect Dis 2011;11:323.  Back to cited text no. 2
Saha SK, Khan NZ, Ahmed AS, Amin MR, Hanif M, Mahbub M, et al. Neurodevelopmental sequelae in pneumococcal meningitis cases in Bangladesh: A comprehensive follow-up study. Clin Infect Dis 2009;48 Suppl 2:S90-6.  Back to cited text no. 3
O'Brien KL, Wolfson LJ, Watt JP, Henkle E, Deloria-Knoll M, McCall N, et al. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: Global estimates. Lancet 2009;374:893-902.  Back to cited text no. 4
Felmingham D, White AR, Jacobs MR, Appelbaum PC, Poupard J, Miller LA, et al. The Alexander Project: The benefits from a decade of surveillance. J Antimicrob Chemother 2005;56 Suppl 2:ii3-21.  Back to cited text no. 5
Song JH, Jung SI, Ko KS, Kim NY, Son JS, Chang HH, et al. High prevalence of antimicrobial resistance among clinical Streptococcus pneumoniae isolates in Asia (an ANSORP study). Antimicrob Agents Chemother 2004;48:2101-7.  Back to cited text no. 6
Weinstein MP, Klugman KP, Jones RN. Rationale for revised penicillin susceptibility breakpoints versus Streptococcus pneumoniae: Coping with antimicrobial susceptibility in an era of resistance. Clin Infect Dis 2009;48:1596-600.  Back to cited text no. 7
Song JH, Jung SI, Ki HK, Shin MH, Ko KS, Son JS, et al. Clinical outcomes of pneumococcal pneumonia caused by antibiotic-resistant strains in Asian countries: A study by the Asian Network for Surveillance of Resistant Pathogens. Clin Infect Dis 2004;38:1570-8.  Back to cited text no. 8
Yu VL, Chiou CC, Feldman C, Ortqvist A, Rello J, Morris AJ, et al. An international prospective study of pneumococcal bacteremia: Correlation with in vitro resistance, antibiotics administered, and clinical outcome. Clin Infect Dis 2003;37:230-7.  Back to cited text no. 9
Pallares R, Liñares J, Vadillo M, Cabellos C, Manresa F, Viladrich PF, et al. Resistance to penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain. N Engl J Med 1995;333:474-80.  Back to cited text no. 10
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing: 18th Informational Supplement. CLSI Document M100-S18. Wayne, PA: Clinical and Laboratory Standards Institute; 2008.  Back to cited text no. 11
Jacobs RF, Kaplan SL, Schutze GE, Dajani AS, Leggiadro RJ, Rim CS, et al. Relationship of MICs to efficacy of cefotaxime in treatment of Streptococcus pneumoniae infections. Antimicrob Agents Chemother 1996;40:895-8.  Back to cited text no. 12
Centers for Disease Control and Prevention (CDC). Effect of new susceptibility breakpoints on reporting of resistance in Streptococcus pneumoniae – United States, 2003. MMWR Morb Mortal Wkly Rep 2004;53:152-4.  Back to cited text no. 13
Centers for Disease Control. Effect of new susceptibility breakpoints on reporting of resistance inStreptococcus pneumoniae– United States, 2006-2007. Morb Mortal Wkly Rep 2008;57:1353-5.  Back to cited text no. 14
Jones RN, Sader HS, Mendes RE, Flamm RK. Update on antimicrobial susceptibility trends among Streptococcus pneumoniae in the United States: Report of ceftaroline activity from the SENTRY Antimicrobial Surveillance Program (1998-2011). Diagn Microbiol Infect Dis 2013;75:107-9.  Back to cited text no. 15
Guo LY, Zhang ZX, Wang X, Zhang PP, Shi W, Yao KH, et al. Clinical and pathogenic analysis of 507 children with bacterial meningitis in Beijing, 2010-2014. Int J Infect Dis 2016;50:38-43.  Back to cited text no. 16
Castillo D, Harcourt B, Hatcher C, Jackson M, Katz L, Mair R, et al. Laboratory Methods for the Diagnosis of Meningitis Caused by Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenza: WHO manual, 2nd ed. Geneva: World Health Organization; 2011.  Back to cited text no. 17
Zhang SX, Rawte P, Brown S, Lo S, Siebert H, Pong-Porter S, et al. Evaluation of CLSI agar dilution method and Trek Sensititre broth microdilution panel for determining antimicrobial susceptibility of Streptococcus pneumoniae. J Clin Microbiol 2011;49:704-6.  Back to cited text no. 18
Clinical and Laboratory Standards Institute (CLSI). Performance standards for antimicrobial susceptibility testing; 26th informational supplement. CLSI document M100-S. Wayne, PA: CLSI; 2016.  Back to cited text no. 19
Lalitha MK, Pai R, John TJ, Thomas K, Jesudason MV, Brahmadathan KN, et al. Serotyping of Streptococcus pneumoniae by agglutination assays: A cost-effective technique for developing countries. Bull World Health Organ 1996;74:387-90.  Back to cited text no. 20
World Health Organization. Coordinated Invasive Bacterial Vaccine Preventable Diseases (IB-VPD) Surveillance Network Case Definitions, Updated January, 2012. Available from: [Last accessed on 2017 Mar 13].  Back to cited text no. 21
Case definitions for pneumococcal syndromes and other severe bacterial infections. Clin Infect Dis 2009;48 Suppl 2:S197-202.  Back to cited text no. 22
Reis JN, Cordeiro SM, Coppola SJ, Salgado K, Carvalho MG, Teixeira LM, et al. Population-based survey of antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae from meningitis patients in Salvador, Brazil. J Clin Microbiol 2002;40:275-7.  Back to cited text no. 23
Berezin EN, Falleiros-Carvalho LH, Lopes CR, Sanajotta AT, Brandileone MC, Menegatti S, et al. Pneumococcal meningitis in children: Clinical findings, most frequent serotypes and outcome. J Pediatr (Rio J) 2002;78:19-23.  Back to cited text no. 24
Alvares JR, Mantese OC, Paula AD, Wolkers PC, Almeida VV, Almeida SC, et al. Prevalence of pneumococcal serotypes and resistance to antimicrobial agents in patients with meningitis: Ten-year analysis. Braz J Infect Dis 2011;15:22-7.  Back to cited text no. 25
Grenón SL, Salvi Grabulosa MC, Regueira MM, Fossati MS, von Specht MH. Pneumococcal meningitis in children under 15 years of age in Misiones (Argentina). Sixteen year's epidemiological surveillance. Rev Argent Microbiol 2014;46:14-23.  Back to cited text no. 26
Demczuk WH, Martin I, Griffith A, Lefebvre B, McGeer A, Lovgren M, et al. Serotype distribution of invasive Streptococcus pneumoniae in Canada after the introduction of the 13-valent pneumococcal conjugate vaccine, 2010-2012. Can J Microbiol 2013;59:778-88.  Back to cited text no. 27
Arditi M, Mason EO Jr., Bradley JS, Tan TQ, Barson WJ, Schutze GE, et al. Three-year multicenter surveillance of pneumococcal meningitis in children: Clinical characteristics, and outcome related to penicillin susceptibility and dexamethasone use. Pediatrics 1998;102:1087-97.  Back to cited text no. 28
Mera RM, Miller LA, Amrine-Madsen H, Sahm DF. Impact of new Clinical Laboratory Standards Institute Streptococcus pneumoniae penicillin susceptibility testing breakpoints on reported resistance changes over time. Microb Drug Resist 2011;17:47-52.  Back to cited text no. 29
European Centre for Disease Prevention and Control. Surveillance of Invasive Pneumococcal Disease in Europe, 2010. Stockholm: ECDC; 2012. Available from: [Last accessed on 2017 Mar 13].  Back to cited text no. 30
Imöhl M, Reinert RR, Tulkens PM, van der Linden M. Penicillin susceptibility breakpoints for Streptococcus pneumoniae and their effect on susceptibility categorisation in Germany (1997-2013). Eur J Clin Microbiol Infect Dis 2014;33:2035-40.  Back to cited text no. 31
Ramdani-Bouguessa N, Ziane H, Bekhoucha S, Guechi Z, Azzam A, Touati D, et al. Evolution of antimicrobial resistance and serotype distribution of Streptococcus pneumoniae isolated from children with invasive and noninvasive pneumococcal diseases in Algeria from 2005 to 2012. New Microbes New Infect 2015;6:42-8.  Back to cited text no. 32
Ziane H, Manageiro V, Ferreira E, Moura IB, Bektache S, Tazir M, et al. Serotypes and antibiotic susceptibility of Streptococcus pneumoniae isolates from invasive pneumococcal disease and asymptomatic carriage in a pre-vaccination period, in Algeria. Front Microbiol 2016;7:803.  Back to cited text no. 33
Nhantumbo AA, Gudo ES, Caierão J, Munguambe AM, Comé CE, Zimba TF, et al. Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae in children with acute bacterial meningitis in Mozambique: Implications for a national immunization strategy. BMC Microbiol 2016;16:134.  Back to cited text no. 34
Saha SK, Baqui AH, Darmstadt GL, Ruhulamin M, Hanif M, El Arifeen S, et al. Comparison of antibiotic resistance and serotype composition of carriage and invasive pneumococci among Bangladeshi children: Implications for treatment policy and vaccine formulation. J Clin Microbiol 2003;41:5582-7.  Back to cited text no. 35
Waisbourd-Zinman O, Bilavsky E, Tirosh N, Samra Z, Amir J. Penicillin and ceftriaxone susceptibility of Streptococcus pneumoniae isolated from cerebrospinal fluid of children with meningitis hospitalized in a tertiary hospital in Israel. Isr Med Assoc J 2010;12:225-8.  Back to cited text no. 36
Kim SH, Song JH, Chung DR, Thamlikitkul V, Yang Y, Wang H, et al. Changing trends in antimicrobial resistance and serotypes of Streptococcus pneumoniae isolates in Asian countries: An Asian Network for Surveillance of Resistant Pathogens (ANSORP) study. Antimicrob Agents Chemother 2012;56:1418-26.  Back to cited text no. 37
Al-Waili BR, Al-Thawadi S, Hajjar SA. Impact of the revised penicillin susceptibility breakpoints for Streptococcus pneumoniae on antimicrobial resistance rates of meningeal and non-meningeal pneumococcal strains. Ann Saudi Med 2013;33:111-5.  Back to cited text no. 38
Moore CE, Giess A, Soeng S, Sar P, Kumar V, Nhoung P, et al. Characterisation of invasive Streptococcus pneumoniae isolated from Cambodian children between 2007-2012. PLoS One 2016;11:e0159358.  Back to cited text no. 39
Phongsamart W, Srifeungfung S, Chatsuwan T, Nunthapisud P, Treerauthaweeraphong V, Rungnobhakhun P, et al. Changing trends in serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae causing invasive diseases in Central Thailand, 2009-2012. Hum Vaccin Immunother 2014;10:1866-73.  Back to cited text no. 40
Su LH, Wu TL, Kuo AJ, Chia JH, Chiu CH. Antimicrobial susceptibility of Streptococcus pneumoniae at a university hospital in Taiwan, 2000-07: Impact of modified non-meningeal penicillin breakpoints in CLSI M100-S18. J Antimicrob Chemother 2009;64:336-42.  Back to cited text no. 41
Xue L, Yao K, Xie G, Zheng Y, Wang C, Shang Y, et al. Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae isolates that cause invasive disease among Chinese children. Clin Infect Dis 2010;50:741-4.  Back to cited text no. 42
Zhao C, Zhang F, Chu Y, Liu Y, Cao B, Chen M, et al. Phenotypic and genotypic characteristic of invasive pneumococcal isolates from both children and adult patients from a multicenter surveillance in China 2005-2011. PLoS One 2013;8:e82361.  Back to cited text no. 43
Pan F, Han L, Huang W, Tang J, Xiao S, Wang C, et al. Serotype distribution, antimicrobial susceptibility, and molecular epidemiology of Streptococcus pneumoniae isolated from children in Shanghai, China. PLoS One 2015;10:e0142892.  Back to cited text no. 44
Jin P, Wu L, Oftadeh S, Kudinha T, Kong F, Zeng Q. Using a practical molecular capsular serotype prediction strategy to investigate Streptococcus pneumoniae serotype distribution and antimicrobial resistance in Chinese local hospitalized children. BMC Pediatr 2016;16:53.  Back to cited text no. 45
Gopi T, Ranjith J, Anandan S, Balaji V. Epidemiological characterisation of Streptococcus pneumoniae from India using multilocus sequence typing. Indian J Med Microbiol 2016;34:17-21.  Back to cited text no. 46
[PUBMED]  [Full text]  
Catalán MJ, Fernández JM, Vazquez A, Varela de Seijas E, Suárez A, Bernaldo de Quirós JC. Failure of cefotaxime in the treatment of meningitis due to relatively resistant Streptococcus pneumoniae. Clin Infect Dis 1994;18:766-9.  Back to cited text no. 47
Klugman KP, Friedland IR, Bradley JS. Bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in cerebrospinal fluid of children with acute bacterial meningitis. Antimicrob Agents Chemother 1995;39:1988-92.  Back to cited text no. 48
Navarro-Torné A, Dias JG, Hruba F, Lopalco PL, Pastore-Celentano L, Gauci AJ; Invasive Pneumococcal Disease Study Group. Risk factors for death from invasive pneumococcal disease, Europe, 2010. Emerg Infect Dis 2015;21:417-25.  Back to cited text no. 49
van de Beek D, Cabellos C, Dzupova O, Esposito S, Klein M, Kloek AT, et al. ESCMID guideline: Diagnosis and treatment of acute bacterial meningitis. Clin Microbiol Infect 2016;22 Suppl 3:S37-62.  Back to cited text no. 50
Antibiotic Guidelines 2015-16, Johns Hopkins Medicine. Treatment Recommendations for Adult Inpatients. Available from: [Last accessed on 2017 Mar 13].  Back to cited text no. 51
McGill F, Heyderman RS, Michael BD, Defres S, Beeching NJ, Borrow R, et al. The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults. J Infect 2016;72:405-38.  Back to cited text no. 52
Le Saux N; Canadian Paediatric Society, Infectious Diseases and Immunization Committee. Guidelines for the management of suspected and confirmed bacterial meningitis in Canadian children older than one month of age. Paediatr Child Health 2014;19:141-52.  Back to cited text no. 53
Swanson D. Meningitis. Pediatr Rev 2015;36:514-26. Available from: 36/12/514.full.pdf. [Last accessed on 2017 Mar 13].  Back to cited text no. 54
Indian Council of Medical Research. Department of Health Research, New Delhi, India, 2017. Treatment Guidelines for Antimicrobial Use in Common Syndromes. Available from: [Last accessed on 2017 Mar 13].  Back to cited text no. 55
Johnson HL, Deloria-Knoll M, Levine OS, Stoszek SK, Freimanis Hance L, Reithinger R, et al. Systematic evaluation of serotypes causing invasive pneumococcal disease among children under five: The pneumococcal global serotype project. PLoS Med 2010;7. pii: e1000348.  Back to cited text no. 56
Barroso DE, Godoy D, Castiñeiras TM, Tulenko MM, Rebelo MC, Harrison LH. ğ-Lactam resistance, serotype distribution, and genotypes of meningitis-causing Streptococcus pneumoniae, Rio de Janeiro, Brazil. Pediatr Infect Dis J 2012;31:30-6.  Back to cited text no. 57
Kyaw MH, Lynfield R, Schaffner W, Craig AS, Hadler J, Reingold A, et al. Effect of introduction of the pneumococcal conjugate vaccine on drug-resistant Streptococcus pneumoniae. N Engl J Med 2006;354:1455-63.  Back to cited text no. 58
Pelton SI, Huot H, Finkelstein JA, Bishop CJ, Hsu KK, Kellenberg J, et al. Emergence of 19A as virulent and multidrug resistant pneumococcus in Massachusetts following universal immunization of infants with pneumococcal conjugate vaccine. Pediatr Infect Dis J 2007;26:468-72.  Back to cited text no. 59
Mittman SA, Huard RC, Della-Latta P, Whittier S. Comparison of BD phoenix to VITEK 2, microscan MICroSTREP, and Etest for antimicrobial susceptibility testing of Streptococcus pneumoniae. J Clin Microbiol 2009;47:3557-61.  Back to cited text no. 60
Charles MK, Berenger BM, Turnbull L, Rennie R, Fuller J. Variability of ğ-lactam susceptibility testing for Streptococcus pneumoniae using 4 commercial test methods and broth microdilution. Diagn Microbiol Infect Dis 2016;84:240-5.  Back to cited text no. 61


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


Print this article  Email this article


2004 - Indian Journal of Medical Microbiology
Published by Wolters Kluwer - Medknow

Online since April 2001, new site since 1st August '04