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Antibiotics

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.

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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

An evolutionary model to predict the frequency of antibiotic resistance under seasonal antibiotic use, and an application to Streptococcus pneumoniae.

Proc Biol Sci. 2017 May 31;284(1855). pii: 20170679. doi: 10.1098/rspb.2017.0679.

An evolutionary model to predict the frequency of antibiotic resistance under seasonal antibiotic use, and an application to Streptococcus pneumoniae.

Blanquart F1, Lehtinen S2,3, Fraser C2,3.

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Abstract

The frequency of resistance to antibiotics in Streptococcus pneumoniae has been stable over recent decades. For example, penicillin non-susceptibility in Europe has fluctuated between 12% and 16% without any major time trend. In spite of long-term stability, resistance fluctuates over short time scales, presumably in part due to seasonal fluctuations in antibiotic prescriptions. Here, we develop a model that describes the evolution of antibiotic resistance under selection by multiple antibiotics prescribed at seasonally changing rates. This model was inspired by, and fitted to, published data on monthly antibiotics prescriptions and frequency of resistance in two communities in Israel over 5 years. Seasonal fluctuations in antibiotic usage translate into small fluctuations of the frequency of resistance around the average value. We describe these dynamics using a perturbation approach that encapsulates all ecological and evolutionary forces into a generic model, whose parameters quantify a force stabilizing the frequency of resistance around the equilibrium and the sensitivity of the population to antibiotic selection. Fitting the model to the data revealed a strong stabilizing force, typically two to five times stronger than direct selection due to antibiotics. The strong stabilizing force explains that resistance fluctuates in phase with usage, as antibiotic selection alone would result in resistance fluctuating behind usage with a lag of three months when antibiotic use is seasonal. While most antibiotics selected for increased resistance, intriguingly, cephalosporins selected for decreased resistance to penicillins and macrolides, an effect consistent in the two communities. One extra monthly prescription of cephalosporins per 1000 children decreased the frequency of penicillin-resistant strains by 1.7%. This model emerges under minimal assumptions, quantifies the forces acting on resistance and explains up to 43% of the temporal variation in resistance.

© 2017 The Authors.

KEYWORDS:

adaptation; antimicrobial resistance; balancing selection; drug resistance; fluctuating selection; microbiology

PMID: 28566489 PMCID: PMC5454275 DOI: 10.1098/rspb.2017.0679

Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae, a promising target for novel antimicrobial agents.

Dalton Trans. 2017 Jun 2. doi: 10.1039/c7dt01350g. [Epub ahead of print]

Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae, a promising target for novel antimicrobial agents.

Monteiro Pedroso M1, Selleck C1, Bilyj J1, Harmer JR2, Gahan LR1, Mitić N3, Standish AJ4, Tierney DL5, Larrabee JA6, Schenk G1.

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Abstract

CpsB is a metal ion-dependent hydrolase involved in the biosynthesis of capsular polysaccharides in bacterial organisms. The enzyme has been proposed as a promising target for novel chemotherapeutics to combat antibiotic resistance. The crystal structure of CpsB indicated the presence of as many as three closely spaced metal ions, modelled as Mn2+, in the active site. While the preferred metal ion composition in vivo is obscure Mn2+ and Co2+ have been demonstrated to be most effective in reconstituting activity. Using isothermal titration calorimetry (ITC) we have demonstrated that, in contrast to the crystal structure, only two Mn2+ or Co2+ ions bind to a monomer of CpsB. This observation is in agreement with magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) data that indicate the presence of two weakly ferromagnetically coupled Co2+ ions in the active site of catalytically active CpsB. While CpsB is known to be a phosphoesterase we have also been able to demonstrate that this enzyme is efficient in hydrolyzing the β-lactam substrate nitrocefin. Steady-state and stopped-flow kinetics measurements further indicated that phosphoesters and nitrocefin undergo catalysis in a conserved manner with a metal ion-bridging hydroxide acting as a nucleophile. Thus, the combined physicochemical studies demonstrate that CpsB is a novel member of the dinuclear metallohydrolase family.

PMID: 28573276 DOI: 10.1039/c7dt01350g

Integrated proteomic and metabolomic analysis reveals that rhodomyrtone reduces the capsule in Streptococcus pneumoniae.

Sci Rep. 2017 Jun 2;7(1):2715. doi: 10.1038/s41598-017-02996-3.

Integrated proteomic and metabolomic analysis reveals that rhodomyrtone reduces the capsule in Streptococcus pneumoniae.

Mitsuwan W1, Olaya-Abril A2, Calderón-Santiago M3, Jiménez-Munguía I2, González-Reyes JA4, Priego-Capote F3, Voravuthikunchai SP1, Rodríguez-Ortega MJ5.

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Abstract

The emergence of antibiotic-resistant pathogenic bacteria is a healthcare problem worldwide. We evaluated the antimicrobial activity of rhodomyrtone, an acylphloroglucinol present in Rhodomyrtus tomentosa leaves, against the human Gram-positive pathogen Streptococcus pneumoniae. The compound exhibited pronounced anti-pneumococcal activity against a broad collection of clinical isolates. We studied the effects at the molecular level by integrated proteomic and metabolomic analysis. The results revealed alterations in enzymes and metabolites involved in several metabolic pathways including amino acid biosynthesis, nucleic acid biosynthesis, glucid, and lipid metabolism. Notably, the levels of two enzymes (glycosyltransferase and UTP-glucose-1-phosphate uridylyltransferase) and three metabolites (UDP-glucose, UDP-glucuronic acid and UDP-N-acetyl-D-galactosamine) participating in the synthesis of the pneumococcal capsule clearly diminished in the bacterial cells exposed to rhodomyrtone. Rhodomyrtone-treated pneumococci significantly possessed less amount of capsule, as measured by a colorimetric assay and visualized by electron microscopy. These findings reveal the utility of combining proteomic and metabolomic analyses to provide insight into phenotypic features of S. pneumoniae treated with this potential novel antibiotic. This can lead to an alternative antibiotic for the treatment of S. pneumoniae infections, because of the growing concern regarding antimicrobial resistance.

PMID: 28578394 PMCID: PMC5457420 DOI: 10.1038/s41598-017-02996-3

Long Persistence of a Streptococcus pneumoniae 23F Clone in a Cystic Fibrosis Patient.

mSphere. 2017 Jun 7;2(3). pii: e00201-17. doi: 10.1128/mSphere.00201-17. eCollection 2017 May-Jun.

Long Persistence of a Streptococcus pneumoniae 23F Clone in a Cystic Fibrosis Patient.

Rieger M1, Mauch H2, Hakenbeck R1.

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Abstract

Streptococcus pneumoniae isolates of serotype 23F with intermediate penicillin resistance were recovered on seven occasions over a period of 37 months from a cystic fibrosis patient in Berlin. All isolates expressed the same multilocus sequence type (ST), ST10523. The genome sequences of the first and last isolates, D122 and D141, revealed the absence of two phage-related gene clusters compared to the genome of another ST10523 strain, D219, isolated earlier at a different place in Germany. Genomes of all three strains carried the same novel mosaic penicillin-binding protein (PBP) genes, pbp2xpbp2b, and pbp1a; these genes were distinct from those of other penicillin-resistant S. pneumoniae strains except for pbp1a of a Romanian S. pneumoniae isolate. All PBPs contained mutations that have been associated with the penicillin resistance phenotype. Most interestingly, a mosaic block identical to an internal pbp2xsequence of ST10523 was present in pbp2x of Streptococcus mitis strain B93-4, which was isolated from the same patient. This suggests interspecies gene transfer from S. pneumoniae to S. mitis within the host. Nearly all genes expressing surface proteins, which represent major virulence factors of S. pneumoniaeand are typical for this species, were present in the genome of ST10523. One exception was the hyaluronidase gene hlyA, which contained a 12-nucleotide deletion within the promoter region and an internal stop codon. The lack of a functional hyaluronidase might contribute to the ability to persist in the host for an unusually long period of time. IMPORTANCEStreptococcus pneumoniae is a common resident in the human nasopharynx. However, carriage can result in severe diseases due to a unique repertoire of pathogenicity factors that are rare in closely related commensal streptococci. We investigated a penicillin-resistant S. pneumoniae clone of serotype 23F isolated from a cystic fibrosis patient on multiple occasions over an unusually long period of over 3 years that was present without causing disease. Genome comparisons revealed an apparent nonfunctional pneumococcus-specific gene encoding a hyaluronidase, supporting the view that this enzyme adds to the virulence potential of the bacterium. The 23F clone harbored unique mosaic genes encoding penicillin resistance determinants, the product of horizontal gene transfer involving the commensal S. mitis as donor species. Sequences identical to one such mosaic gene were identified in an S. mitis strain from the same patient, suggesting that in this case S. pneumoniaeplayed the role of donor.

KEYWORDS:

23F clone; Streptococcus pneumoniae; cystic fibrosis; hyaluronidase; penicillin-binding proteins; persistence

PMID: 28596991 PMCID: PMC5463027 DOI: 10.1128/mSphere.00201-17

The Alpha-Tocopherol Form of Vitamin E Boosts Elastase Activity of Human PMNs and Their Ability to Kill Streptococcus pneumoniae.

Front Cell Infect Microbiol. 2017 May 3;7:161. doi: 10.3389/fcimb.2017.00161. eCollection 2017.

The Alpha-Tocopherol Form of Vitamin E Boosts Elastase Activity of Human PMNs and Their Ability to Kill Streptococcus pneumoniae.

Bou Ghanem EN1, Lee JN1, Joma BH2, Meydani SN3, Leong JM1, Panda A3.

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Abstract

Despite the availability of vaccines, Streptococcus pneumoniae remains a leading cause of life-threatening infections, such as pneumonia, bacteremia and meningitis. Polymorphonuclear leukocytes (PMNs) are a key determinant of disease course, because optimal host defense requires an initial robust pulmonary PMN response to control bacterial numbers followed by modulation of this response later in infection. The elderly, who manifest a general decline in immune function and higher basal levels of inflammation, are at increased risk of developing pneumococcal pneumonia. Using an aged mouse infection model, we previously showed that oral supplementation with the alpha-tocopherol form of vitamin E (α-Toc) decreases pulmonary inflammation, in part by modulating neutrophil migration across lung epithelium into alveolar spaces, and reverses the age-associated decline in resistance to pneumococcal pneumonia. The objective of this study was to test the effect of α-Toc on the ability of neutrophils isolated from young (22-35 years) or elderly (65-69 years) individuals to migrate across epithelial cell monolayers in response to S. pneumoniae and to kill complement-opsonized pneumococci. We found that basal levels of pneumococcal-induced transepithelial migration by PMNs from young or elderly donors were indistinguishable, suggesting that the age-associated exacerbation of pulmonary inflammation is not due to intrinsic properties of PMNs of elderly individuals but rather may reflect the inflammatory milieu of the aged lung. Consistent with its anti-inflammatory activity, α-Toc treatment diminished PMN migration regardless of donor age. Unexpectedly, unlike previous studies showing poor killing of antibody-opsonized bacteria, we found that PMNs of elderly donors were more efficient at killing complement-opsonized bacteria ex vivo than their younger counterparts. We also found that the heightened antimicrobial activity in PMNs from older donors correlated with increased activity of neutrophil elastase, a serine protease that is required to kill pneumococci. Notably, incubation with α-Toc increased PMN elastase activity from young donors and boosted their ability to kill complement-opsonized pneumococci. These findings demonstrate that α-Toc is a potent modulator of PMN responses and is a potential nutritional intervention to combat pneumococcal infection.

KEYWORDS:

S. pneumoniae; aging; infection; inflammation; neutrophils; serine proteases; vitamin E

PMID: 28516066 PMCID: PMC5413490 DOI: 10.3389/fcimb.2017.00161

Susceptibility of streptococcus pneumoniae to fluoroquinolones and macrolides in upper respiratory tract infections.

Wiad Lek. 2017;70(2):224-226.

Susceptibility of streptococcus pneumoniae to fluoroquinolones and macrolides in upper respiratory tract infections.

Mykhalko YO1, Duhovych TV1, Kish PP2.

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Abstract

INTRODUCTION:

Streptococcal species are known as the most common cause of bacterial upper respiratory tract infections (URTI). Once bacterial infection is diagnosed it demands empirical antibiotic prescription. On the other hand antimicrobial resistance is a global burden in today's medicine. For that reason, knowing of antimicrobial susceptibility patterns in population is an important background for successful treatment of bacterial caused URTI. The aim of this study was to analyze S. pneumoniae resistance and susceptibility patterns to fluoroquinolones and macrolides in URTI.

MATERIALS AND METHODS:

The results of microbiological examination of 2,055 pharyngeal swabs taken from patients with bacterial caused tonsillitis, pharyngitis and laryngitis were analyzed. Antimicrobial susceptibility testing for levofloxacin, ofloxacin, gatifloxacin, erythromycin, clarithromycin, azithromycin was performed with the disk-diffusion method.

RESULTS:

The incidence of S. pneumoniae in the etiological structure of bacterial caused URTI was increasing from 22.47% of cases in 2011 to 36.48% in 2015. The susceptibility of this microorganism to ofloxacin, gatifloxacin and levofloxacin decreased from 96.25%, 100% and 95.00% in 2011 to 44.22%, 65.99% and 62.59% in 2015 respectively. The susceptibility of S. pneumoniae to erythromycin, azithromycin and clarithromycin also decreased from 30.00%, 63.75% and 41.25% in 2011 to 6.80%, 26.53%, 27.21 in 2015.

CONCLUSIONS:

Among investigated antibiotics levofloxacin can be recommended for empiric therapy of URTI because of high pneumococci susceptibility to this drug.

KEYWORDS:

fluoroquinolones; macrolides ; susceptibility; Streptococcus pneumoniae

PMID: 28511165

Genome Evolution to Penicillin Resistance in Serotype 3 Streptococcus pneumoniae by Capsular Switching.

Antimicrob Agents Chemother. 2017 Jun 19. pii: AAC.00478-17. doi: 10.1128/AAC.00478-17. [Epub ahead of print]

Genome Evolution to Penicillin Resistance in Serotype 3 Streptococcus pneumoniae by Capsular Switching.

Chiba N1,2, Murayama SY3, Morozumi M1, Iwata S1, Ubukata K4.

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Abstract

Streptococcus pneumoniae of serotype 3 was collected from cases of invasive pneumococcal disease (n = 124) throughout Japan from April 2010 to March 2013. A penicillin-resistant S. pneumoniae (PRSP) isolate from an adult patient, KK0981 of serotype 3, was identified among these strains. Whole-genome analysis characterized this PRSP as a recombinant strain derived from PRSP of serotype 23F with the cps-locus (20.3 kb) replaced by that of a penicillin-susceptible strain of serotype 3.

Copyright © 2017 American Society for Microbiology.

PMID: 28630198 DOI: 10.1128/AAC.00478-17

Tokai J Exp Clin Med. 2017 Apr 20;42(1):37-40.

Performance Evaluation of a Newly Developed and Fully Automated Bacteriological Analyzer "RAISUS ANY" for Antimicrobial Susceptibility Testing of Fastidious Bacteria Haemophilus influenzae and Streptococcus pneumoniae.

Ohshima T1, Nomiya S, Yamamoto Y, Miyazawa M, Ohsuga J, Hisada A, Iwawaki K, Asai S, Miyachi H.

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Abstract

OBJECTIVE:

Antimicrobial susceptibility testing for fastidious bacteria, such as Haemophilus influenzae (H. influenzae) and Streptococcus pneumoniae (S. pneumoniae) has been performed manually. We evaluated the performance of a newly developed fully automated system for rapid bacterial identification and antimicrobial susceptibility testing "RAISUS ANY" (Nissui Pharmaceutical Co., Ltd.).

METHODS:

We evaluated the performance of "RAISUS ANY" for measurement of minimal inhibitory concentrations (MICs) of H. influenzae and S. pneumoniae, in comparison with the manual method (DP34, Eiken Chem. Co., Ltd.). The repeatability of MICs was studied using the reference strain of these bacteria, obtained from the American Type Culture Collection (ATCC, Manassas, VA, USA).

RESULTS:

The comparison with the manual method for 35 and 36 clinical strains of H. influenzae and S. pneumonia showed 62.9-100% and 86.1-100% agreement, respectively. Five of 35 H. influenzae strains that showed a trailing effect were stably and accurately measured for MICs without a variation among the examiners.

CONCLUSION:

In conclusion, the automated system "RAISUS ANY" provided a reliable MICs data for H. influenzae and S. pneumonia, suggesting its improvement in performance and reliability for routine antimicrobial susceptibility testing in clinical bacteriological laboratories.

PMID: 28413870

[Indexed for MEDLINE]

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.

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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

Braz J Infect Dis. 2017 May 1. pii: S1413-8670(16)30619-5. doi: 10.1016/j.bjid.2017.03.011. [Epub ahead of print]

Serotype changes and antimicrobial nonsusceptibility rates of invasive and non-invasive Streptococcus pneumoniae isolates after implementation of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Bulgaria.

Setchanova L1, Murdjeva M2, Stancheva I3, Alexandrova A4, Sredkova M5, Stoicheva T6, Yoneva M7, Kurchatova A8, Mitov I4.

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Abstract

The 10-valent pneumococcal conjugate vaccine (PCV10) has been included in Bulgarian Childhood Immunization Program since 2010. This study aimed to assess serotype distribution and antimicrobial resistance of 198 invasive and non-invasive Streptococcus pneumoniae strains that had been isolated in Bulgaria during 2011-2016 from patients with invasive (IPD) and non-invasive (NIPD) pneumococcal diseases. The most common invasive serotypes were 3 (10.1%), 19F (4.0%), and 7F (3.0%). A significant decrease in the proportion of invasive vaccine types (VTs) from 64.2% to 35.2% was found in comparison with pre-vaccine era. The most common serotypes among middle ear fluids were 3, 19A and 19F (5.6% each), and VTs fell down from 66.4% to 40.0% in post-PCV10 period. Among respiratory isolates, the most prevalent serotypes were some emergent serotypes such as 15A/B/C (5.0%), 19A, and 6C (4.0% each). VTs decreased significantly (16.3%) among vaccinated children compared to unvaccinated children and adults (44.0%). Two non-VTs (19A and 6C) have increased significantly more (p<0.05) in vaccinated children than in unvaccinated patients. The rates of antibiotic nonsusceptible S. pneumoniae in Bulgaria remained high in post-PCV10 era. Among all source of isolates, antimicrobial nonsusceptibility rates were: oral penicillin - 46.5%, trimethoprim-sulfamethoxazole - 45.4%, erythromycin - 43.9%, tetracycline - 37.4%, and multidrug-resistance (MDR) was 44%. The most common MDR serotypes were 19F, 19A, 6A/C, 15A/B/C and 23A. Our results proved that PCV10 vaccination substantially reduced VTs pneumococcal IPD and NIPD. There has been a shift in the distribution of S. pneumoniae serotypes mostly in vaccinated children but also in the whole population and strong serotype-specific antibiotic resistance was observed after vaccine implementation. Therefore, it is important to continue monitoring serotype changes and pneumococcal resistance among all patient ages in addition to aid in determining the long-term effectiveness of PCV10 interventions.

Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

KEYWORDS:

Antimicrobial nonsusceptibility; Invasive and non-invasive isolates; Serotypes; Streptococcus pneumoniae

PMID: 28472614 DOI: 10.1016/j.bjid.2017.03.011

Molecular characterization of penicillin non-susceptible Streptococcus pneumoniae isolated before and after pneumococcal conjugate vaccine implementation in Casablanca, Morocco.

Ann Clin Microbiol Antimicrob. 2017 Apr 4;16(1):23. doi: 10.1186/s12941-017-0200-6.

Molecular characterization of penicillin non-susceptible Streptococcus pneumoniae isolated before and after pneumococcal conjugate vaccine implementation in Casablanca, Morocco.

Diawara I1,2, Barguigua A3, Katfy K4,5, Nayme K4,6, Belabbes H4,5, Timinouni M6, Zerouali K4,5, Elmdaghri N4,5.

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Abstract

BACKGROUND:

Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide, especially among children and the elderly. The ability to effectively treat pneumococcal infection has been compromised due to the acquisition of antibiotic resistance, particularly to β-lactam drugs. This study aimed to describe the prevalence and molecular evolution of penicillin non-susceptible S. pneumoniae (PNSP) isolated from invasive diseases before and after pneumococcal conjugate vaccine implementation in Casablanca, Morocco.

METHODS:

Isolates were obtained from the Microbiology Laboratory of Ibn Rochd University Hospital Centre of Casablanca. Serogrouping was done by Pneumotest Kit and serotyping by the Quellung capsular swelling. Antibiotic susceptibility pattern was determined by disk diffusion and E-test methods. The PNSP were analyzed by pulsed-field gel electrophoresis (PFGE) and by genotyping of pbp1a, pbp2b, and pbp2x genes.

RESULTS:

A total of 361 S. pneumoniae isolates were collected from 2007 to 2014. Of these isolates, 58.7% were obtained before vaccination (2007-2010) and 41.3% after vaccination (2011-2014). Of the 361 isolates, 80 were PNSP (22.2%). Generally, the proportion of PNSP between pre- and post-vaccination periods were 31 and 13% (p = 0.009), respectively. The proportion of PNSP isolated from pediatric and adult (age > 14 years) patients decreased from 34.5 to 22.9% (p = 0.1) and from 17.7 to 10.2% (p = 0.1) before and after vaccine implementation, respectively. The leading serotypes of PNSP were 14 (33 vs. 57%) and 19A (18 vs. 14%) before and after vaccination among children. For adults, serotypes 19A (53%) and 23F (24%) were the dominant serotypes in the pre-vaccination period, while serotype 14 (22%) was the most prevalent after vaccination. There were 21 pbp genotypes in the pre-vaccination period vs. 12 for post-vaccination period. PFGE clustering showed six clusters of PNSP grouped into three clusters specific to pre-vaccination period (clusters I, II and III), two clusters specific to post-period (clusters V and VI) and a cluster (IV) that contained clones belonging to the two periods of vaccination.

CONCLUSION:

Our observations demonstrate a high degree of genetic diversity among PNSP. Genetic clustering among PNSP strains showed that they spread mainly by a restricted number of PNSP clones with vaccine serotypes. PFGE clustering combined with pbp genotyping revealed that vaccination can change the population structure of PNSP.

KEYWORDS:

Antibiotic resistance; Invasive pneumococcal disease; PFGE; Penicillin-binding proteins; Serotypes; Streptococcus pneumoniae; β-lactams

PMID: 28376809 PMCID: PMC5381081 DOI: 10.1186/s12941-017-0200-6