The impact of pneumococcal conjugate vaccines on carriage of and disease caused by Streptococcus pneumoniae serotypes 6C and 6D in southern Israel.

The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) followed by PCV13 resulted in a dramatic reduction in carriage and disease rates of Streptococcus pneumoniae (Sp) serotype 6B (Sp6B) and Sp6A. The structural modifications of the capsule of Sp6A and Sp6B to become Sp6C and Sp6D, respectively, raised a concern that eradication of Sp6A/Sp6B by PCV could be accompanied by an increase in Sp6C/Sp6D. This study examines the dynamics and clonal distribution of Sp6C/Sp6D relative to Sp6A/Sp6B during 1999-2014, pre- and post-PCV implementation. Sp were cultured from Blood/CSF and MEF of children <2 years, and from conjunctiva and nasopharynx of children <5 years. PCR was applied for Sp6C and Sp6D identification. Clonality was determined by PFGE and MLST. PCV introduction resulted in decreased carriage rates and conjunctivitis caused by serogroup 6 serotypes. Incidence of Sp6A, Sp6B and Sp6D in otitis media dropped gradually along with PCV7/13 introduction, whereas Sp6C rates increased in the PCV7 period and then decreased following PCV13 implementation. In invasive pneumococcal disease, complete elimination of serogroup 6 was found in the PCV era. Similar clonal composition was found for Sp6C and Sp6D pre- and post-PCV. We conclude that Sp6C and Sp6D do not act as replacement serotypes for Sp6A and Sp6B following vaccination with PCV13. The major Sp6C and Sp6D clones present pre-PCV persisted also post-PCV implementation, suggesting that these clones possess an advantage retained post-vaccination.

Outbreaks of Invasive Kingella kingae Infections in Closed Communities.

OBJECTIVES: To describe the results of the epidemiologic investigation of outbreaks of invasive Kingella kingae infections among attendees at daycare facilities located in 4 closed communities in Israel. STUDY DESIGN: The preschool-aged population of communities with clusters of Kingella cases had oropharyngeal cultures performed. K kingae isolates from infected patients and healthy contacts were genotyped by pulsed field gel electrophoresis to determine the spread of outbreak strains. RESULTS: The affected closed communities (3 military bases and 1 "kibbutz" commune) were characterized by tight social and family networks and intensive mingling. The outbreaks affected 9 of 51 attendees (attack rate: 17.6%) age 8-19 months (median: 12 months), within a 21-day period. Cases included skeletal system infections (n = 8) and bacteremia (n = 1); K kingae isolates were confirmed by the use of blood culture vials and selective media. Clinical presentation was mild and acute-phase reactants were usually normal or only moderately elevated. Thirty out of 55 (54.5%) asymptomatic children carried the outbreak strains. Analysis of the 3 clusters in which the entire preschool-aged population was cultured revealed that 31 of 71 (43.7%) children younger than 24 months of age were colonized with K kingae organisms compared with 8 of 105 (7.6%) older children (P < .001). CONCLUSIONS: Clusters of invasive K kingae infections characterized by sudden onset, high attack rate, and wide dissemination of the outbreak strain can occur in daycare facilities and closed communities. Because the mild clinical presentation of invasive K kingae infections and the fastidious nature of the organism, a high index of suspicion and use of sensitive detection methods are recommended.

Baseline epidemiology and genetic structure of Streptococcus pneumoniae serotype 6D in southern Israel prior to introduction of pneumococcal conjugate vaccines.

We characterized Streptococcus pneumoniae serotype 6D from among previously identified S. pneumoniae serotype 6B strains from Jewish and Bedouin children in southern Israel during a decade before vaccination. S. pneumoniae serotype 6D isolates constituted 6.7% of the presumed S. pneumoniae serotype 6B isolates. S. pneumoniae serotype 6D strains belonged to 20 sequence types that were differentially distributed between the two ethnic groups.

Clonal distribution of common pneumococcal serotypes not included in the 7-valent conjugate vaccine (PCV7): marked differences between two ethnic populations in southern Israel.

This study aimed to compare the clonal distribution of common pneumococcal strains not included in the 7-valent pneumococcal conjugate vaccine (PCV7) that were isolated from cases of acute otitis media (AOM) and invasive pneumococcal disease (IPD) in two distinct ethnic populations in southern Israel during the decade (1999 to 2008) preceding PCV7 implementation. Isolates recovered from Jewish and Bedouin children <5 years old were characterized by antibiotic resistance and molecular epidemiology using pulsed-field gel electrophoresis and multilocus sequence typing. Of 5,236 AOM and 425 IPD isolates, 43% and 57% were from Jewish and Bedouin children, respectively. PCV7 accounted for 54% and 45% of the AOM and IPD episodes, respectively. Eleven major non-PCV7 serotypes (1, 3, 5, 6A, 7F, 12F, 15B/C, 19A, 21, 33F, and 35B) constituted 31% and 42% of the AOM and IPD episodes, respectively. The clonal distributions of the 11 non-PCV7 serotypes and their antibiotic susceptibilities were significantly different among the two ethnic populations in both the AOM and IPD groups. About half of the AOM and IPD cases resulted from non-PCV7 pneumococci, even before PCV7 implementation. The significant differences between the two ethnic populations suggest that lifestyle and microenvironment are major determinants in the clonal distribution of disease-causing pneumococci. Post-PCV7 surveillance is important in understanding non-PCV7 clonal expansion in the two distinct populations.

Epidemiology of invasive Kingella kingae infections in 2 distinct pediatric populations cohabiting in one geographic area.

The annual incidence of invasive Kingella kingae infection in children younger than 4 years of age was significantly higher in westernized Jews than in indigent Bedouins living side by side in southern Israel (12.21/100,000 and 5.83/100,000, respectively, (P < 0.05). One K. kingae clone was overrepresented among isolates from Jewish children, suggesting that differences in bacterial pathogenicity may contribute to the morbidity excess detected in this population group.

Dissemination of Kingella kingae in the community and long-term persistence of invasive clones.

BACKGROUND: Although Kingella kingae is being increasingly recognized as an important pediatric pathogen, our current understanding of the transmission of the organism is limited. The dissemination of K. kingae in the community was studied in 2 ethnic groups living side-by-side in Southern Israel. METHODS: Organisms recovered from oropharyngeal cultures, obtained from healthy young Jewish and Bedouin children during a 12-month period, were typed by pulsed-field gel electrophoresis and compared. RESULTS: Isolates from Bedouin children usually differed from those derived from Jews, confirming the relative social isolation of the 2 populations and the importance of close mingling in the spread of K. kingae. Significant clustering of genotypic clones in households and Bedouin neighborhoods was observed, indicating person-to-person transmission through intimate contact. Organisms detected in the study were identical to historical isolates recovered over the last 15 years from respiratory carriers and patients with bacteremia or skeletal infections. CONCLUSIONS: The present study demonstrates that children may be asymptomatically colonized in the respiratory tract by virulent K. kingae clones. The organism is transmitted from child-to-child through intimate contact. Some strains exhibit increased fitness and are maintained in the population for prolonged periods.

An international serotype 3 clone causing pediatric noninvasive infections in Israel, Costa Rica, and Lithuania.

BACKGROUND: Serotype 3 is known for its ability to cause invasive diseases worldwide. In the United States, after introduction of the 7-valent pneumococcal conjugate vaccine (PCV7), the prevalence of a serotype 3 clone (Netherlands-31/ST180) increased. The present study was aimed to evaluate the importance of serotype 3 clones in noninvasive infections in Israel, Costa Rica, and Lithuania. METHODS: Molecular typing and antibiotic resistance were performed on 77 serotype 3 strains recovered from pediatric noninvasive infections during 2003-2005, and on 50 carried strains from healthy carriers. RESULTS: Serotype 3 ranked second among isolates from noninvasive infections in Costa Rica and Lithuania, and seventh among the Israeli isolates. Pulsed field gel electrophoresis (PFGE) analysis revealed the presence of 1 major cluster (64/77, 83%); this cluster comprised 60/64 fully susceptible strains that corresponded to the Netherlands-31/ST180 clone, and 4/64 multidrug-resistant strains, all from Lithuania, that corresponded to ST505, a double locus variant of ST180. Two additional fully susceptible clones, ST458 (11/77, 14%) and ST1116 (2/77, 3%), were found among the Israeli and Costa Rican strains, respectively. The same PFGE clusters identified among noninvasive infections were found among 50 isolates from carriers, with the same molecular characteristics. CONCLUSIONS: Serotype 3 accounts for a large proportion of mucosal disease in children, even before the introduction of PCV7. The data presented here describe for the first time the importance of a multidrug-resistant serotype 3 clone, ST505, in noninvasive infections.

The important role of nontypable Streptococcus pneumoniae international clones in acute conjunctivitis.

BACKGROUND: In a recent epidemiological study in southern Israel, nontypable Streptococcus pneumoniae isolates were found to be highly associated with sporadic cases of acute conjunctivitis (AC). The purpose of the present study was to evaluate the relative importance in causing AC of the absence of capsule versus genotype properties. METHODS: DNA typing by pulsed-field gel electrophoresis (PFGE) was performed on 148 nontypable organisms isolated from 3 sites: nasopharynx of healthy children, middle-ear fluid, and conjunctiva. RESULTS: Analysis of the PFGE patterns revealed the presence of 6 clusters; 2 clusters that included 44% of the isolates (65/148) were associated with AC, and the remaining 4 were frequently isolated from the nasopharynx. Multilocus sequence typing, performed on representative isolates of the 2 major clusters, confirmed that the organisms were pneumococci; one is a single-locus variant of sequence type (ST) 448, and the other is related to ST344. Both types appear to be members of pneumococcal lineages that have lost capsular loci. The nontypable isolates showed high rates of resistance to antimicrobial agents. CONCLUSIONS: Our data suggest that the absence of the capsule--along with other, yet-unidentified genetic characteristics--provide S. pneumoniae with a selective virulence advantage in conjunctivitis.

Outbreak of Kingella kingae skeletal system infections in children in daycare.

OBJECTIVE: The objective of this study is to describe the investigation of an outbreak of one culture-proven and two presumptive cases of Kingella kingae osteomyelitis detected within a 15-day period in a daycare center in Israel. METHODS: Surveillance pharyngeal cultures were obtained from all attendees at the index daycare center and from two neighboring facilities. Combined amoxicillin-rifampin prophylaxis was administered to all children aged 6 to 30 months living in the community. K. kingae isolates were typed by pulsed field gel electrophoresis, random amplified polymorphic DNA analysis and sequencing of the rRNA genes. RESULTS: Surveillance cultures showed that four of 11 attendees at the index facility as well as five of 12 and one of 15 attendees at neighboring daycare centers carried K. kingae. Typing of isolates showed that the isolate from a child with osteomyelitis was identical to all other isolates from the same daycare center and different from organisms derived from the other facilities. Administration of prophylactic antibiotics resulted in partial eradication of the organism. CONCLUSIONS: Dissemination of K. kingae in a susceptible pediatric population may result in an outbreak of invasive disease. Our experience suggests the need for increased alertness for clusters of K. kingae infections among children in daycare.

Emergence of penicillin-nonsusceptible Streptococcus pneumoniae clones expressing serotypes not present in the antipneumococcal conjugate vaccine.

BACKGROUND: Penicillin-nonsusceptible Streptococcus pneumoniae isolates are confined mainly to a few serogroups. Capsular transformation may serve as a mechanism for spreading antibiotic resistance to new serotypes. METHODS: Antibiogram and molecular typing, by pulsed-field gel electrophoresis (PFGE), were performed on 46 nasopharyngeal and middle ear fluid (MEF) isolates expressing serotype 11A, 45 MEF isolates expressing serotype 15B/C (recovered during 1998-2003 from Israeli children <5 years old), and 57 MEF isolates expressing serotype 19F (recovered during 1998-2001 from Costa Rican children <7.5 years old). RESULTS: PFGE patterns showed that 49 (86%) of 57 serotype 19F isolates and 19 (41%) of 46 serotype 15B/C isolates were closely related. The vast majority of these isolates (80% of serotype 19F and 100% of serotype 15B/C isolates) were nonsusceptible to penicillin. Multilocus sequence typing (MLST) data show that the serotype 15B/C isolates belonged to the ST346 cluster, whereas the serotype 19F isolates were a single-locus variant of ST346. For serotype 11A isolates, PFGE patterns and MLST analysis showed that 8 (80%) of the 10 penicillin-nonsusceptible isolates belonged to a single clone--namely, ST156--which was identical to the international Spain9V-3 clone. CONCLUSIONS: Penicillin-nonsusceptible pneumococcal clones of serotypes not related to those included in the 11-valent conjugate vaccines may derive from capsular transformation of vaccine-related serotypes. Of particular concern was the detection of serotype 11A variants of the successful international Spain9V-3 clone. This phenomenon, although seemingly rare at present, can have implications for the long-term effectiveness of the conjugate vaccines.

Four antibiotic-resistant Streptococcus pneumoniae clones unrelated to the pneumococcal conjugate vaccine serotypes, including 2 new serotypes, causing acute otitis media in southern Israel.

This study examined the prevalence of antibiotic-resistant clones that belong to serotypes not included in the pneumococcal conjugate vaccines and that cause a significant percentage of acute otitis media (AOM) in children in southern Israel. During 1998-2001, 2467 pneumococcal isolates, obtained from middle-ear fluid of children <3 years old with AOM, were characterized by antimicrobial susceptibility testing, serotype testing, and pulsed-field gel electrophoresis. Non-vaccine type (NVT) strains constituted 477 (19%) of the 2467 isolates, of which 173 (36%) belonged to only 4 serotypes: 35B, 33F, 21, and 15B/C. For serotype 35B, 47 (96%) of 49 strains were penicillin nonsusceptible, and 93% constituted a single clone; for serotype 33F, 31 (82%) of 38 strains were penicillin nonsusceptible, and 95% constituted a single clone; for serotype 21, 38 (93%) of 41 strains were penicillin nonsusceptible, and 93% constituted a single clone; for serotype 15B/C, 22 (49%) of 45 strains were penicillin nonsusceptible, and 42% constituted a single clone. Two of these clones have not been described elsewhere. The high prevalence of NVT clones should increase the awareness of the potential for replacement of the vaccine strains with these NVT antibiotic-resistant strains.

Genetic relatedness of resistant and multiresistant Streptococcus pneumoniae strains, recovered in the Athens area, to international clones.

The prevalence of resistance to antibiotics was examined among 318 Streptococcus pneumoniae strains isolated during 1998 and 1999 in a children's hospital in Athens. The rate of resistance to penicillin was 25.8% (intermediate 22%, resistant 3.8%); 42.5% of the strains were resistant to > or = 1 antibiotic and 20% were multidrug resistant. Resistance to penicillin was lowest in invasive strains (8.3%) and highest in ear isolates (31%). A review of the same microbiology laboratory's records revealed that there has been a gradual increase in penicillin resistance since 1988-1989, when it was 5%. Capsular types were determined for 77 strains resistant to > or = 1 antibiotic, and 69 (90%) of them belonged to the following five serotypes: 19F, 14, 9V, 23F, and 6B. Seventy-five strains were analyzed by pulsed-field gel electrophoresis (PFGE) and 59/75 (79%) shared five electrophoretic types. The largest cluster consisted of 19 serotype 19F strains, of which 18 were nonsusceptible to penicillin and most were multidrug resistant and shared a common and distinct electrophoretic pattern not resembling any known clone. A group of 17 strains that were nonsusceptible to penicillin belonged to serotypes 9V (10), 14 (6), and 19F (1) and shared a common PFGE type similar to the international clone Spain9V-3. Seven serotype 23F strains, of which five were multidrug resistant, belonged to the international clone Spain23F-1. Among the strains susceptible to penicillin but resistant to non-beta-lactam antibiotics, the largest cluster consisted of 13 isolates resistant to erythromycin that belonged to serotype 14 and shared an electrophoretic pattern characteristic of the clone England14-9. Finally, three serotype 6B strains were penicillin susceptible and multidrug resistant and had features similar to the Mediterranean 6B clone. The introduction and spread of several antibiotic-resistant international clones accounts at least in part for the increase in pneumococcal resistance observed in recent years in the Athens metropolitan area.

Community-acquired methicillin-resistant Staphylococcus aureus in institutionalized adults with developmental disabilities.

Methicillin-resistant Staphylococcus aureus (MRSA) has recently been reported to emerge in the community setting. We describe the investigation and control of a community-acquired outbreak of MRSA skin infections in a closed community of institutionalized adults with developmental disabilities. In a 9-month period in 1997, 20 (71%) of 28 residents had 73 infectious episodes. Of the cultures, 60% and 32% obtained from residents and personnel, respectively, grew S. aureus; 96% and 27% were MRSA. All isolates were genetically related by pulsed-field gel electrophoresis and belonged to a phage type not previously described in the region. No known risk factors for MRSA acquisition were found. However, 58 antibiotic courses had been administered to 16 residents during the preceding 9 months. Infection control measures, antibiotic restriction, and appropriate therapy resulted in successful termination of this outbreak. Selective antibiotic pressure may result in the emergence, persistence, and dissemination of MRSA strains, causing prolonged disease.