ABSTRACT
Streptococcus pneumoniae is one of the most common bacteria causing community-acquired pneumonia and meningitis. The use of 7-valent pneumococcal conjugate vaccine (PCV7) has reduced the incidence of pneumococcal disease while changing pneumococcal population through herd immunity and non-vaccine pneumococci replacement. This study investigated molecular epidemiologic characteristics of pneumococcal strains in the Kinki region of Japan from 2008 to 2013. A total of 159 invasive pneumococcal isolates were characterized by serotyping, antibiotic susceptibility testing, PCR analysis of penicillin-binding protein genes, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). In adult populations, pediatric PCV7 introduction decreased isolates expressing PCV7 serotypes via herd immunity and increased isolates expressing non-PCV7 serotypes. The rate of penicillin resistance and isolates with alterations in all three pbp genes was higher in PCV7 type isolates than in non-PCV7 type isolates. In MLST analysis, all of serotype 19F isolates were of the same sequence type, ST236, which is the antimicrobial-resistant clone Taiwan19F-14, and the majority of serotypes 23F and 19A isolates were of ST1437 and ST3111 respectively, which are the predominant clones of antimicrobial-resistant pneumococci in Japan. In PFGE profiles, serotype 6B-ST2224, serotype 19F-ST236, serotype 19A-ST3111, and serotype 23F-ST1437 formed six separate clusters composed of genetically identical strains, and genetically identical serotype 22F-ST433 formed two different clusters between the pre- and post-PCV7 period. The results of molecular analysis suggest the spread and persistence of these identical antimicrobial resistant clones in the Kinki region and genetic changes of epidemic clone serotype 22F-ST433 before and after pediatric PCV7 introduction.
Subject(s)
Heptavalent Pneumococcal Conjugate Vaccine/therapeutic use , Pneumococcal Infections/epidemiology , Streptococcus pneumoniae/classification , Streptococcus pneumoniae/genetics , Adolescent , Adult , Child , Community-Acquired Infections/epidemiology , Community-Acquired Infections/genetics , Community-Acquired Infections/microbiology , Community-Acquired Infections/prevention & control , Electrophoresis, Gel, Pulsed-Field , Humans , Immunologic Factors/therapeutic use , Japan/epidemiology , Microbial Sensitivity Tests , Molecular Epidemiology , Multilocus Sequence Typing , Penicillin Resistance , Penicillin-Binding Proteins/genetics , Pneumococcal Infections/genetics , Pneumococcal Infections/microbiology , Pneumococcal Infections/prevention & control , Serogroup , Serotyping , Streptococcus pneumoniae/isolation & purification , Vaccines, Conjugate/therapeutic useABSTRACT
BACKGROUND: Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP). This cross-sectional study aimed to determine the prevalence of macrolide-resistant M. pneumoniae strains in a convenience series of 234 adult hospitalised and nonhospitalised subjects with a diagnosis of CAP in January 2013 to April 2015 in South Italy. METHODS: Respiratory samples were subjected to real-time PCR. In M. pneumoniae-positive samples, domain V of 23S rRNA was sequenced to detect resistance-conferring point mutations. P1 major adhesion protein typing and multiple loci variable-number tandem repeat analysis (MLVA) were also performed. RESULTS: Of the 234 samples, 15 (6.4%) were positive for M. pneumoniae. Three of these had a macrolide-resistant genotype: two and one had A2063G and A2064G mutations, respectively. Fourteen of the 15 strains were subtyped: half had subtype 1 and half had subtype 2. Eight strains underwent MLVA profiling: one each had the J, A, and Z type. The remainder was unclassifiable. CONCLUSIONS: This novel discovery of macrolide-resistant M. pneumoniae strains in adults with CAP in Italy suggests that there may be increasing circulation of these strains in the population. To facilitate rapid optimization of the antibiotic strategy in Italy, macrolide resistance should be monitored by a surveillance system that is based on molecular methods.
Subject(s)
Community-Acquired Infections/drug therapy , Drug Resistance, Bacterial/genetics , Macrolides/therapeutic use , Pneumonia, Mycoplasma/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Community-Acquired Infections/epidemiology , Community-Acquired Infections/genetics , Community-Acquired Infections/microbiology , Female , Genotype , Humans , Italy/epidemiology , Macrolides/adverse effects , Male , Microbial Sensitivity Tests , Middle Aged , Minisatellite Repeats/genetics , Mutation , Mycoplasma pneumoniae/drug effects , Mycoplasma pneumoniae/genetics , Mycoplasma pneumoniae/pathogenicity , Pneumonia, Mycoplasma/epidemiology , Pneumonia, Mycoplasma/genetics , Pneumonia, Mycoplasma/microbiology , Young AdultABSTRACT
OBJECTIVE: To determine the susceptibility of bacterial respiratory tract pathogens, isolated from children (0-12 years) as part of the global PROTEKT surveillance study (1999-2000), to a range of antibacterials, including the ketolide telithromycin. METHODS: Minimum inhibitory concentrations of the antibacterials studied were determined at a central laboratory using the NCCLS microdilution broth method. Macrolide resistance mechanisms were detected by PCR. RESULTS: Of 779 Streptococcus pneumoniae isolates worldwide, 43% were non-susceptible to penicillin (18% intermediate; 25% resistant) and 37% were resistant to erythromycin, with considerable intercountry variation. Eighteen per cent of 653 Haemophilus influenzae and >90% of 316 Moraxella catarrhalis isolates produced beta-lactamase. Of 640 Streptococcus pyogenes isolates, 10% were resistant to erythromycin, with considerable intercountry variation. All S. pneumoniae and 99.8% of H. influenzae isolates were susceptible to telithromycin using breakpoints proposed to the NCCLS (Subject(s)
Anti-Bacterial Agents/therapeutic use
, Community-Acquired Infections/microbiology
, Drug Resistance, Bacterial
, Ketolides
, Respiratory Tract Infections/microbiology
, Community-Acquired Infections/drug therapy
, Community-Acquired Infections/epidemiology
, Community-Acquired Infections/genetics
, Drug Resistance, Multiple
, Female
, Global Health
, Humans
, Macrolides/therapeutic use
, Male
, Microbial Sensitivity Tests
, Polymerase Chain Reaction
, Population Surveillance
, Respiratory Tract Infections/drug therapy
, Respiratory Tract Infections/epidemiology
, Respiratory Tract Infections/genetics
ABSTRACT
In recent years, antibacterial resistance among respiratory pathogens implicated in community-acquired respiratory tract infections (RTIs) has spread worldwide at an alarming rate. Thus, there is a pressing need for new antibacterials that retain activity against resistant organisms, have a low potential to select for resistance and do not induce cross-resistance. Telithromycin is the first of a new class of antibacterials - the ketolides - that have been designed specifically to overcome resistance among respiratory tract pathogens. This paper presents the first results of the PROTEKT study (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin), a worldwide surveillance study initiated to chart the prevalence of important resistance phenotypes and genotypes and the comparative activity of telithromycin against such strains. Analysis of over 7,000 bacterial isolates by April 2001 has confirmed the notable prevalence of strains resistant to commonly prescribed RTI antibacterials for all the pathogens studied. Telithromycin demonstrates high activity against isolates of Streptococcus pneumoniae, irrespective of penicillin G, macrolide or fluoroquinolone resistance. Telithromycin is also highly active against other respiratory tract pathogens, including Streptococcus pyogenes and beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis. These data justify the assertion that telithromycin is a promising new candidate for the empirical treatment of community-acquired RTIs, particularly in the face of increasing antibacterial resistance.