Viewing entries in
Epidemiology

Streptococcus pneumoniae serotype 19A: Worldwide epidemiology.

Expert Rev Vaccines. 2017 Aug 7. doi: 10.1080/14760584.2017.1362339. [Epub ahead of print]

Streptococcus pneumoniae serotype 19A: Worldwide epidemiology.

Isturiz R1, Sings HL1, Hilton B1, Arguedas A2, Reinert RR3, Jodar L1.

Author information

Abstract

INTRODUCTION:

Streptococcus pneumoniae causes mucosal and invasive diseases with high morbidity and mortality. Introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) into routine infant immunization programs worldwide resulted in serotype 19A becoming a leading cause of the remaining pneumococcal disease burden in vaccinated and unvaccinated individuals. This article reviews the impact of the latest generation PCVs (10-valent PCV, PCV10, and 13-valent PCV, PCV13) on serotype 19A. Areas covered: This article covers immune responses elicited by PCV7, PCV10 and PCV13 against serotype 19A and their impact on nasopharyngeal (NP) carriage and disease in vaccinated and unvaccinated populations using data from surveillance systems, randomized controlled trials, and observational studies. Expert commentary: As expected from a PCV containing serotype 19A, PCV13 elicits significantly higher functional immune responses against serotype 19A than PCV7 and PCV10. Higher responses are likely to be linked to both direct impact in vaccinated populations and reductions in 19A NP carriage in children, thus inducing herd protection and reducing 19A invasive pneumococcal disease (IPD) in nonvaccinated children and adults. In contrast, PCV7 and PCV10 have shown mixed evidence of direct short-lived cross-protection and little to no impact on 19A carriage, resulting in continued transmission and disease.

KEYWORDS:

Antimicrobial resistance; Streptococcus pneumoniae; epidemiology; invasive pneumococcal disease; nasopharyngeal carriage; pneumococcal conjugate vaccines; serotype 19A

PMID: 28783380 DOI: 10.1080/14760584.2017.1362339

Current challenges in the accurate identification of Streptococcus pneumoniae and its serogroups/serotypes in the vaccine era.

J Microbiol Methods. 2017 Aug 2;141:48-54. doi: 10.1016/j.mimet.2017.07.015. [Epub ahead of print]

Current challenges in the accurate identification of Streptococcus pneumoniae and its serogroups/serotypes in the vaccine era.

Varghese R1, Jayaraman R1, Veeraraghavan B2.

Author information

Abstract

Streptococcus pneumoniae is a major cause of pneumonia, meningitis and other invasive diseases resulting in high mortality and morbidity among children under the age of five. Inaccurate identification of S. pneumoniae masks the exact estimation of disease burden and could delay treatment options. This is the common problem most frequently faced in developing countries due to several reasons that include poor infrastructure, insensitive operational procedures and lack of expertise. Inconsistent methods for phenotypic detection often delay the early identification and confirmation of S. pneumoniae. For serotyping S. pneumoniae, Quellung method is the gold standard which can be performed only on viable isolates, needs expertise and is expensive. Therefore, the data available on disease burden and serotype prevalence is not truly estimated in most of the developing countries, in turn, the use of available pneumococcal vaccines have been restricted. This current review deliberates an overview on advantages and limitations of routinely used phenotypic tests for S. pneumoniae identification. Also discussed in this review are the roles and current challenges faced by various molecular identification and serogroup/serotype identification methods of S. pneumoniae, including PCR, real time PCR, sequence analysis of different specific genes of S. pneumoniae, PCR combined with RFLP, MALDI-TOF, MLST, MLSA and WGS.

Copyright © 2017 Elsevier B.V. All rights reserved.

KEYWORDS:

Accurate identification; Limitations; Molecular methods; S. pneumoniae; Serotyping

PMID: 28780272 DOI: 10.1016/j.mimet.2017.07.015

Assessment of a novel bile solubility test and MALDI-TOF for the differentiation of Streptococcus pneumoniae from other mitis group streptococci.

Sci Rep. 2017 Aug 2;7(1):7167. doi: 10.1038/s41598-017-07772-x.

Assessment of a novel bile solubility test and MALDI-TOF for the differentiation of Streptococcus pneumoniae from other mitis group streptococci.

Slotved HC1, Facklam RR2, Fuursted K3.

Author information

Abstract

This study assesses a novel bile solubility test and MALDI-TOF for the differentiation of Streptococcus pneumoniae from other mitis group streptococci, including differentiation of S. pneumoniae from Streptococcus pseudopneumoniae. Eighty-four species verified mitis group isolates were subjected to our bile solubility test (which measures and calculates the differences of absorbance in the test tube containing 10% sodium deoxycholate versus a blank control tube, after incubation for 10 minutes at 36 °C using a spectrophotometer) and MALDI-TOF MS (both the standard result output and by visual spectra evaluation). Applying a calculated optimal cut-off absorbance-value of 2.1, differentiated S. pneumoniae from all but one other mitis group streptococci (one S. mitis isolate generated an OD-value above 2.1). MALDI-TOF score value identification identified correctly 46 S. pneumoniae and 4 S. pseudopneumoniae but misidentified 16 other mitis group strains. Visual spectra evaluation correctly identified all S. pneumoniae and S. pseudopneumoniae strains but misidentified 13 other mitis group strains. The bile solubility test based on spectrophotometric reading described in this study can differentiate S. pneumoniae from other Streptococcus species. Combining the bile solubility test and the MALDI-TOF spectra results provide a correct identification of all S. pneumoniae and S. pseudopneumoniae isolates.

PMID: 28769078 PMCID: PMC5540920 DOI: 10.1038/s41598-017-07772-x

Fluorescence Imaging of Streptococcus pneumoniae with the Helix pomatia agglutinin (HPA) As a Potential, Rapid Diagnostic Tool.

Front Microbiol. 2017 Jul 18;8:1333. doi: 10.3389/fmicb.2017.01333. eCollection 2017.

Fluorescence Imaging of Streptococcus pneumoniae with the Helix pomatia agglutinin (HPA) As a Potential, Rapid Diagnostic Tool.

Domenech M1,2, García E1,2.

Author information

Abstract

Streptococcus pneumoniae is a common human pathogen and a major causal agent of life-threatening infections that can either be respiratory or non-respiratory. It is well known that the Helix pomatia (edible snail) agglutinin (HPA) lectin shows specificity for terminal αGalNAc residues present, among other locations, in the Forssman pentasaccharide (αGalNAc1→3βGalNAc1→3αGal1→4βGal1→4βGlc). Based on experiments involving choline-independent mutants and different growth conditions, we propose here that HPA recognizes the αGalNAc terminal residues of the cell wall teichoic and lipoteichoic acids of S. pneumoniae. In addition, experimental evidence showing that pneumococci can be specifically labeled with HPA when growing as planktonic cultures as well as in mixed biofilms of S. pneumoniae and Haemophilus influenzae has been obtained. It should be underlined that pneumococci were HPA-labeled despite of the presence of a capsule. Although some non-pneumococcal species also bind the agglutinin, HPA-binding combined with fluorescence microscopy constitutes a suitable tool for identifying S. pneumoniae and, if used in conjunction with Gram staining and/or other suitable technique like antigen detection, it may potentially facilitate a fast and accurate diagnosis of pneumococcal infections.

KEYWORDS:

Forssman antigen; Streptococcus pneumoniae; binding lectins; fluorescence microscopy; teichoic acids

PMID: 28769901 PMCID: PMC5513899 DOI: 10.3389/fmicb.2017.01333

Development of PCRSeqTyping-a novel molecular assay for typing of Streptococcus pneumoniae.

Pneumonia (Nathan). 2017 May 25;9:8. doi: 10.1186/s41479-017-0032-3. eCollection 2017.

Development of PCRSeqTyping-a novel molecular assay for typing of Streptococcus pneumoniae.

Nagaraj G1, Ganaie F1, Govindan V1, Ravikumar KL1.

Author information

Abstract

BACKGROUND:

Precise serotyping of pneumococci is essential for vaccine development, to better understand the pathogenicity and trends of drug resistance. Currently used conventional and molecular methods of serotyping are expensive and time-consuming, with limited coverage of serotypes. An accurate and rapid serotyping method with complete coverage of serotypes is an urgent necessity. This study describes the development and application of a novel technology that addresses this need.

METHODS:

Polymerase chain reaction (PCR) was performed, targeting 1061 bp cpsB region, and the amplicon was subjected to sequencing. The sequence data was analyzed using the National Centre for Biotechnology Information database. For homologous strains, a second round of PCR, sequencing, and data analysis was performed targeting 10 group-specific genes located in the capsular polysaccharide region. Ninety-one pneumococcal reference strains were analyzed with PCRSeqTyping and compared with Quellung reaction using Pneumotest Kit (SSI, Denmark).

RESULTS:

A 100% correlation of PCRSeqTyping results was observed with Pneumotest results. Fifty-nine reference strains were uniquely identified in the first step of PCRSeqTyping. The remaining 32 homologous strains out of 91 were also uniquely identified in the second step.

CONCLUSION:

This study describes a PCRSeqTyping assay that is accurate and rapid, with high reproducibility. This assay is amenable for clinical testing and does not require culturing of the samples. It is a significant improvement over other methods because it covers all pneumococcal serotypes, and it has the potential for use in diagnostic laboratories and surveillance studies.

KEYWORDS:

Molecular serotyping; PCRSeqTyping; Streptococcus pneumoniae; cpsB sequencing

PMID: 28702310 PMCID: PMC5471960 DOI: 10.1186/s41479-017-0032-3

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

Indian J Med Microbiol. 2017 Apr-Jun;35(2):228-236. doi: 10.4103/ijmm.IJMM_17_124.

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

Verghese VP1, Veeraraghavan B2, Jayaraman R2, Varghese R2, Neeravi A2, Jayaraman Y3, Thomas K4, Mehendale SM3.

Author information

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.

PMID: 28681811 DOI: 10.4103/ijmm.IJMM_17_124

Conjugation of PspA4Pro with capsular Streptococcus pneumoniae polysaccharide serotype 14 does not reduce the induction of cross-reactive antibodies.

Clin Vaccine Immunol. 2017 Jun 21. pii: CVI.00118-17. doi: 10.1128/CVI.00118-17. [Epub ahead of print]

Conjugation of PspA4Pro with capsular Streptococcus pneumoniae polysaccharide serotype 14 does not reduce the induction of cross-reactive antibodies.

da Silva MA1, Converso TR1,2, Gonçalves VM1, Leite LCC1, Tanizaki MM1, Barazzone GC3.

Author information

Abstract

Current pneumococcal vaccines are composed of bacterial polysaccharides as antigens plain or conjugated to carrier proteins. While efficacious against vaccine serotypes, epidemiologic data shows increasing incidence of infections caused by non-vaccine serotypes of Streptococcus pneumoniae. The use of Pneumococcal surface protein A (PspA) as a carrier protein in a conjugate vaccine could help preventing serotype replacement by increasing vaccine coverage and reducing selective pressure of S. pneumoniae serotypes. PspA is present in all pneumococcal strains, is highly immunogenic and is known to induce protective antibodies. Based on its sequence, PspA has been classified into 3 families and 6 clades. A PspA fragment derived from family 2 clade 4 (PspA4Pro) was shown to generate antibodies with a broad-range of cross-reactivity, across clades and families. Here, PspA4Pro was modified and conjugated to capsular polysaccharide serotype 14 (PS14). We investigated the impact of conjugation on the immune response induced to PspA4Pro and PS14. Mice immunized with the PS14-mPspA4Pro conjugate produced higher titers of anti-PS14 antibodies than the animals that received co-administered antigens. Both conjugated and co-administered PS14 and mPspA4Pro induced antibodies with opsonophagocytic activity against PS14-carrying strain as well as against a panel of strains bearing PspAs from five clades (encompassing families 1 and 2) bearing a non-PS14 serotype. Furthermore, mice immunized with PS14-mPspA4Pro were protected against nasal colonization with a non-related S. pneumoniae strain bearing PspA from clade 1, serotype 6B. These results demonstrate that the cross-reactivity mediated by PspA4Pro is retained following conjugation, supporting the use of PspA4 as a carrier protein in order to enhance pneumococcal vaccine coverage and encourage its further investigation as a candidate in future vaccine designs.

Copyright © 2017 American Society for Microbiology.

PMID: 28637805 DOI: 10.1128/CVI.00118-17

10-valent pneumococcal conjugate vaccine (PCV10) decreases metabolic activity but not nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae.

Vaccine. 2017 Jun 28. pii: S0264-410X(17)30841-1. doi: 10.1016/j.vaccine.2017.06.048. [Epub ahead of print]

10-valent pneumococcal conjugate vaccine (PCV10) decreases metabolic activity but not nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae.

Andrade DC1, Borges IC2, Bouzas ML2, Oliveira JR2, Fukutani KF3, Queiroz AT3, de Oliveira CI4, Barral A4, Van Weyenbergh J5, Nascimento-Carvalho C6.

Author information

Abstract

BACKGROUND:

The effect of pneumococcal vaccination is widely variable when measured by nasopharyngeal carriage of vaccine and non-vaccine targets. The aim of this study was to compare the carriage rates and metabolic activity of Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae and Moraxella catarrhalis among children who were or were not vaccinated with PCV10.

METHODS:

We included children with acute respiratory infection aged 6-23months from a cross-sectional study (CHIADO-IVAS). Nasopharyngeal aspirates were collected and respiratory pathogens were quantified by nCounter digital transcriptomics (Nanostring) and metagenomic sequencing of 16S ribosomal RNA (Illumina). The metabolic rate was calculated by the ratio between RNA transcripts and 16S DNA reads.

RESULTS:

Out of the 80 patients in this study, 53 were vaccinated with PCV10 and 27 were unvaccinated. There was no difference in nasopharyngeal carriage rates of S. pneumoniae, S. aureus, H. influenzae or M. catarrhalis by either transcriptomic analysis or 16S metagenomics. However, unvaccinated children presented a higher metabolic rate for S. pneumoniae compared to PCV10-vaccinated children (Median [25-75th percentiles]: 126 [22.75-218.41] vs. 0[0-47.83], p=0.004). Furthermore, unvaccinated children presented a positive correlation between mRNA counts and 16S DNA reads for S. pneumoniae (r=0.707; p<0.001) and H. influenzae (r=0.525; p=0.005), in contrast to vaccinated children. No such effect was observed for S. aureus and M. catarrhalis.

CONCLUSIONS:

Vaccination by PCV10 exerts a pathogen-specific effect on pneumococcal metabolic rate. Pathogen RNA/DNA ratio might represent a more sensitive readout for vaccine follow-up, as compared to nasopharyngeal carriage.

Copyright © 2017 Elsevier Ltd. All rights reserved.

KEYWORDS:

Capsular polysaccharides; Metabolism; Nasopharyngeal colonization; Protein D

PMID: 28668567 DOI: 10.1016/j.vaccine.2017.06.048

Phylogenetic analysis of emergent Streptococcus pneumoniae serotype 22F causing invasive pneumococcal disease using whole genome sequencing.

PLoS One. 2017 May 22;12(5):e0178040. doi: 10.1371/journal.pone.0178040. eCollection 2017.

Phylogenetic analysis of emergent Streptococcus pneumoniae serotype 22F causing invasive pneumococcal disease using whole genome sequencing.

Demczuk WHB1, Martin I1, Hoang L2, Van Caeseele P3, Lefebvre B4, Horsman G5, Haldane D6, Gubbay J7, Ratnam S8, German G9, Daley Bernier J10, Strudwick L11, McGeer A12, Zhanel GG13, Van Domselaar G1,14, Graham M1,14, Mulvey MR1.

Author information

Abstract

Since implementation of the 13-valent polyvalent conjugate vaccine (PCV13) in Canada during 2010, the proportion of PCV13 serotypes causing invasive pneumococcal disease (IPD) has declined from 55% (n = 1492) in 2010 to 31% (n = 764) in 2014. A concurrent increase of non-PCV13 serotypes has occurred and 22F has become the most prevalent serotype in Canada increasing from 7% (n = 183) to 11% (n = 283). Core single nucleotide variant phylogenetic analysis was performed on 137 Streptococcus pneumoniae serotype 22F isolates collected across Canada from 2005-2015. Six phylogenetic lineages (n = 117) were identified among a serotype 22F/ST433 clonal complex (CC), including a recently expanding erythromycin-resistant clone. Erythromycin-resistance was observed in 25 isolates possessing ermB, mef or a 23S rRNA A2061G point mutation; 2 penicillin-resistant isolates had recombinant pbp1a, pbp2a and/or pbp2x; 3 tetracycline-resistant isolates contained tetM; and 1 isolate was multidrug-resistant. Virulence factor analysis indicated a high level of homogeneity among the 22F/ST433 clonal complex strains. A group of 6 phylogenetic outlier strains had differing MLST, antimicrobial resistance and molecular profiles suggestive of capsule switching events. While capsule switch events among S. pneumoniae serotype 22F has been observed, increasing prevalence of S. pneumoniae serotype 22F can be attributed to an evolving homogenous clone expanding nationally through local transmission events.

PMID: 28531208 PMCID: PMC5439729 DOI: 10.1371/journal.pone.0178040

Clinically Relevant Detection of Streptococcus pneumoniae with DNA-Antibody Nanostructures.

Anal Chem. 2017 Jun 20;89(12):6900-6906. doi: 10.1021/acs.analchem.7b01508. Epub 2017 Jun 8.

Clinically Relevant Detection of Streptococcus pneumoniae with DNA-Antibody Nanostructures.

Wang J1, Leong MC1, Leong EZW1, Kuan WS2,3, Leong DT1.

Author information

Abstract

Streptococcus pneumoniae (SP) is a pathogenic bacterium and a major cause of community-acquired pneumonia that could be fatal if left untreated. Therefore, rapid and sensitive detection of SP is crucial to enable targeted treatment during SP infections. In this study, DNA tetrahedron (DNA TH) with a hollow structure is anchored on gold electrodes to construct an electrochemical immunosensor for rapid detection of pneumococcal surface protein A (PspA) peptide and SP lysate from synthetic and actual human samples. This DNA nanostructure-based immunosensor displays excellent electrochemical activity toward PspA with a sensitive linear region from 0 to 8 ng/mL of PspA peptide and a low limit of detection (LOD) of 0.218 ng/mL. In addition, this DNA-TH-based immunosensor exhibits good sensing performance toward SP lysate in a clinically relevant linear range from 5 to 100 CFU/mL with a LOD of 0.093 CFU/mL. Along with these attractive features, this electrochemical immunosensor is able to specifically recognize and detect the PspA peptide mixed with other physiologically relevant components like bovine serum albumin (BSA) and lipopolysaccharide. In addition, our sensor could detect SP lysate even when dispersed in BSA or Escherichia coli lysate. Lastly, uncultured samples from the nasal cavity, mouth, and axilla of a human subject could be successfully determined by this well-designed electrochemical immunosensor.

PMID: 28548485 DOI: 10.1021/acs.analchem.7b01508

Epidemiology of culture-confirmed infections of Streptococcus pneumoniae (2012-2015) and nasopharyngeal carriage in children and households in Taiwan (2014-2015).

J Med Microbiol. 2017 Jun;66(6):729-736. doi: 10.1099/jmm.0.000488. Epub 2017 Jun 8.

Epidemiology of culture-confirmed infections of Streptococcus pneumoniae (2012-2015) and nasopharyngeal carriage in children and households in Taiwan (2014-2015).

Janapatla RP1, Su LH2, Chen HH3, Chang HJ1, Tsai TC4, Chen PY5, Chen CL1, Chiu CH6.

Author information

Abstract

PURPOSE:

An observational study was performed to investigate the carriage rate and serotypes of Streptococcus pneumoniae in the 13-valent pneumococcal conjugate vaccine (PCV13) era in Taiwan.

METHODOLOGY:

From March 2014 to March 2015 a total of 500 healthy children and their households (631 adults) were enrolled from two large medical centres for nasopharyngeal carriage survey. Clinical isolates were prospectively collected from June 2012 to May 2015 at Chang Gung Memorial Hospital. We applied a multiplex polymerase chain reaction in addition to culture to detect S. pneumoniae.

RESULTS:

S. pneumoniae was isolated from 12.0 % of the children and 3.6 % of the households. In the children's cohort only 23.3 % of the isolates could be assigned to PCV13 serotypes; non-vaccine serotypes were predominant (76.6 %) and the most frequently detected non-vaccine serotypes were 15A/F and 15B/C (both 13.3 %), followed by 23A (6.7 %). In the household cohort, 21.7 % belonged to PCV13 serotypes, and 78.3 % to non-vaccine serotypes. Clinical analysis of culture-confirmed pneumococcal infection showed that infection caused by PCV13 serotypes decreased by 47 % from 83 % in 2012-2013 to 44 % in 2014-2015, while infection caused by non-PCV13 serotypes increased from 17 to 56 %. Among the carriage isolates a significantly higher percentage belonged to serogroup 15 compared to serogroup 19 (26.6 vs 6.66 %, 2014-2015; P=0.003). Therefore, clinical isolates belonging to serogroup 15 were more prevalent than those belonging to serogroup 19 (44.1 vs 32.3 %, 2014-2015; P=0.318).

CONCLUSION:

The isolation of non-vaccine serotypes and unknown serotypes after the introduction of PCV13 in children highlights the importance of continued surveillance for emerging serotypes.

PMID: 28590240 DOI: 10.1099/jmm.0.000488

Antimicrobial Resistant Streptococcus pneumoniae: Prevalence, Mechanisms, and Clinical Implications.

Am J Ther. 2017 May;24(3):e361-e369. doi: 10.1097/MJT.0000000000000551.

Antimicrobial Resistant Streptococcus pneumoniae: Prevalence, Mechanisms, and Clinical Implications.

Cherazard R1, Epstein M, Doan TL, Salim T, Bharti S, Smith MA.

Author information

Abstract

BACKGROUND:

Streptococcus pneumoniae is a major cause of pneumonia, meningitis, sepsis, bacteremia, and otitis media. S. pneumoniae has developed increased resistance to multiple classes of antibiotics.

STUDY DESIGN:

Systematic literature review of prevalence, mechanisms, and clinical implications in S. pneumoniae resistance.

AREAS OF UNCERTAINTY:

Since S. pneumoniae resistance to penicillin was first reported with subsequent development of resistance to other classes of drugs, selection of appropriate antibiotic treatment is challenging.

DATA SOURCES:

We searched PubMed (English language) for citations to antibiotic resistance in S. pneumoniae published before March 1, 2016.

RESULTS:

We present a review of S. pneumoniae resistance to beta-lactams, macrolides, lincosamides, fluoroquinolones, tetracyclines, and trimethoprim-sulfamethoxazole (TMP-SMX). There has been a steady decline in susceptibility of S. pneumoniae to commonly used beta-lactams. Phenotypic expression of penicillin resistance occurs as a result of a genetic structural modification in penicillin-binding proteins. Between 20% and 40% of S. pneumoniae isolates are resistant to macrolides. Macrolide resistance mechanisms include ribosomal target site alteration, alteration in antibiotic transport, and modification of the antibiotic. Approximately 22% of S. pneumoniae isolates are resistant to clindamycin. Similar to macrolide resistance, clindamycin involves a target site alteration. The prevalence of fluoroquinolone resistance is low, although increasing. S. pneumoniae resistance to fluoroquinolones occurs by accumulated mutations within the bacterial genome, increased efflux, or acquisition of plasmid-encoded genes. S. pneumoniae resistance has also increased for the tetracyclines. The primary mechanism is mediated by 2 genes that confer ribosomal protection. The prevalence of TMP-SMX resistance is around 35%. As with fluoroquinolones, resistance to TMP-SMX is secondary to mutations in the bacterial genome.

CONCLUSIONS:

Effective treatment of resistant S. pneumoniae is a growing concern. New classes of drugs, newer formulations of older drugs, combination antibiotic therapy, nonantibiotic modalities, better oversight of antibiotic usage, and enhanced preventive measures hold promise.

PMID: 28430673 DOI: 10.1097/MJT.0000000000000551