Increasing Incidence of Penicillin- and Cefotaxime-resistant Streptococcus pneumoniae Causing Meningitis in India: Time for Revision of Treatment Guidelines?

Verghese, Valsan Philip; Veeraraghavan, Balaji; Jayaraman, Ranjith; Varghese, Rosemol; Neeravi, Ayyanraj; Jayaraman, Yuvaraj; Thomas, Kurien; Mehendale, Sanjay

doi:10.4103/ijmm.ijmm_17_124

Cited by 32 publications

(11 citation statements)

References 49 publications

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“…The data for patients belonging to all age groups were reviewed from seven studies. 35 – 41 Unlike the majority of the studies that reported the predominance of bacterial meningitis, Yerramilli et al ., 37 in an observational study, reported a high prevalence of aseptic/viral meningitis (39%). The majority of the studies reported bacterial meningitis.…”

Section: Resultsmentioning

confidence: 99%

A systematic literature review on the prevalence and etiology of meningitis among critically ill and hospitalized patients in India

Ghia

Rambhad

2021

Therapeutic Advances in Infection

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Background: In India, owing to multiple factors, such as insufficient laboratory capacity, poor reporting systems due to limited access to healthcare facilities and limited disease surveillance programmes, the actual disease burden of meningitis is unknown and may be largely under-reported. Objective: A systematic literature review was performed to describe: (a) the prevalence of meningitis; and (b) its etiological pathogen across different regions, age groups and patients with comorbidities. Method: A systematic literature search was conducted between 1990 and 2020 using PubMed and Google Scholar databases to identify Indian studies reporting the prevalence rates and etiology of meningitis. A total of 51 studies were included in the final analysis. Results: A total of 38 studies reported prevalence of meningitis and 21 studies reported data on the etiology of meningitis in India. These studies included mixed patient populations: (a) pyogenic meningitis; (b) meningitis in sick or hospitalized patients with tuberculosis, acute febrile encephalopathy syndrome, septicaemia, invasive pneumococcal disease or respiratory compromise; and (c) meningitis patients with comorbidities. The prevalence of confirmed bacterial meningitis in the pediatric population (0–14 years) ranged between 0.5% and 61.8%. A total of seven studies reported the prevalence of meningitis in patients of all age groups (0–75 years), with prevalence ranging between 8.68% and 78.85%. Cryptococcal meningitis was predominant in patients with positive HIV/AIDS, with a prevalence ranging between 2.09% and 53.1%. Streptococcus pneumoniae was found to be the predominant pathogen causing meningitis across different regions of India, with a frequency ranging from 4% to 61.8% in patients of all age groups. Conclusion: This systematic literature review displayed the possible range of frequency of bacterial meningitis pathogens across a wide variety of age groups in different regions of India. Further studies are warranted to monitor meningitis cases, which may facilitate the development of prevention and treatment strategies in India.

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Section: Resultsmentioning

confidence: 99%

A systematic literature review on the prevalence and etiology of meningitis among critically ill and hospitalized patients in India

Ghia

Rambhad

2021

Therapeutic Advances in Infection

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“…resistance in S. pneumoniae gradually increased in India from 9.5% in 2008 to 42.8% in 2016, while cefotaxime nonsusceptibility increased from 4.7% in 2008 to 28.5% in 2016 among meningeal isolates (Verghese et al, 2017).…”

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confidence: 98%

Emergence of Meropenem Resistance Among Cefotaxime Non-susceptible Streptococcus pneumoniae: Evidence and Challenges

et al. 2022

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The principal causative agent of acute bacterial meningitis (ABM) in children and the elderly is Streptococcus pneumoniae, with a widespread increase in penicillin resistance. Resistance is due to non-synonymous single-nucleotide polymorphisms (nsSNPs) that alter the penicillin-binding proteins (PBPs), the targets for all β-lactam drugs. Hence, resistance against one β-lactam antibiotic may positively select another. Since meropenem is an alternative to cefotaxime in meningeal infections, we aim to identify whether nsSNPs in the PBPs causing penicillin and cefotaxime resistance can decrease the pneumococcal susceptibility to meropenem. Comparison of the nsSNPs in the PBPs between the cefotaxime-resistant Indian (n = 33) and global isolates (n = 28) revealed that nsSNPs in PBP1A alone elevated meropenem minimal inhibitory concentrations (MICs) to 0.12 μg/ml, and nsSNPs in both PBP2X and 2B combined with PBP1A increases MIC to ≥ 0.25 μg/ml. Molecular docking confirmed the decrease in the PBP drug binding affinity due to the nsSNPs, thereby increasing the inhibition potential and the MIC values, leading to resistance. Structural dynamics and thermodynamic stability pattern in PBPs as a result of mutations further depicted that the accumulation of certain nsSNPs in the functional domains reduced the drug affinity without majorly affecting the overall stability of the proteins. Restricting meropenem usage and promoting combination therapy with antibiotics having non-PBPs as targets to treat cefotaxime non-susceptible S. pneumoniae meningitis can prevent the selection of β-lactam resistance.

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“…Bhutan, Maldives, Sri Lanka and Thailand had the lowest U5M and pneumococcal deaths among studied countries, and the highest burden was in India (e.g., high case-fatality due to IPD in young children) [32]. Antibiotic resistance to penicillin was estimated at 10% (range up to 20%) for IPD overall in India [12], however considerably higher rates of nearly 60% were reported when considering meningitis isolates [33]. Sri Lanka, on the other hand, had lower mortality numbers, yet high resistance to almost all antibiotics.…”

Section: Discussionmentioning

confidence: 88%

Invasive Pneumococcal Disease burden and PCV coverage in children under five in Southeast Asia: implications for India

Kolhapure

Yewale²,

Agrawal

et al. 2021

J Infect Dev Ctries

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Introduction: Pneumococcal diseases, though preventable, are a major public health problem in Southeast Asia and particularly in India. Pneumococcal conjugate vaccines (PCVs) are used in the region for over a decade, but to understand their impact, invasive pneumococcal diseases (IPD) burden and PCV coverage data in the region are needed. Methodology: A literature search was conducted to identify i) key evidence published between February 2008 and February 2018 on IPD burden, serotype prevalence and antibiotic resistance in Southeast Asia, and ii) PCV serotype and vaccination coverage in Southeast Asia. Results: 49 relevant articles were included in the final analysis. Mortality in children under 5 years remains high in Southeast Asian countries, with around 25% of deaths due to IPD in India and Pakistan. There was a lack of recent data on IPD incidence. Antibiotic resistance to IPD isolates is increasing, with high resistance rates especially for meningeal isolates. Based on serotype distribution data, primarily for India, available PCVs would cover around 70-80% of IPD-causing serotypes. Vaccine coverage was around 15-20% in India to 98% in South Korea. Conclusions: Widespread PCV use could successfully reduce IPD burden in the region due to high serotype coverage by available PCVs; emphasis should be placed on increasing vaccination uptake, for every child, particularly in India. Reducing health system barriers and improving surveillance and awareness is essential to improve coverage and effectively prevent IPD morbidity and mortality particularly in at risk regions.

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Increasing Incidence of Penicillin- and Cefotaxime-resistant Streptococcus pneumoniae Causing Meningitis in India: Time for Revision of Treatment Guidelines?

Cited by 32 publications

References 49 publications

A systematic literature review on the prevalence and etiology of meningitis among critically ill and hospitalized patients in India

A systematic literature review on the prevalence and etiology of meningitis among critically ill and hospitalized patients in India

Emergence of Meropenem Resistance Among Cefotaxime Non-susceptible Streptococcus pneumoniae: Evidence and Challenges

Invasive Pneumococcal Disease burden and PCV coverage in children under five in Southeast Asia: implications for India

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