Invasive Streptococcus pneumoniae from Portugal: implications for vaccination and antimicrobial therapy

The distribution of pneumococcal serotypes among 465 invasive isolates recovered from 1999 to 2002 in Portugal was analysed by age group. Serotype 14 was either the most prevalent or the second most prevalent in all age groups. Among children aged < 2 years, serotypes 6B and 23F, which are usually associated with children, together with serotypes 19A and 14, accounted for more than half of the isolates. In contrast, in older adults (> or = 60 years), serotypes 3, 14, 1, 8 and 4 were the most prevalent. The potential coverage of the seven-valent conjugate vaccine is 63.2% among infants, and does not change significantly if children aged < 6 years are considered, which is a lower coverage than in other European countries. The potential coverage of the 23-valent polysaccharide vaccine is high in all age groups, particularly among older adults (80.7%). All isolates were tested for their susceptibility to penicillin, cefuroxime, cefotaxime, vancomycin, erythromycin, clindamycin, levofloxacin, gatifloxacin, moxifloxacin, linezolid, quinupristin-dalfopristin, tetracycline, chloramphenicol and trimethoprim-sulphamethoxazole. Most isolates collected from children aged < 6 years had decreased susceptibility to at least one antibiotic class, whereas isolates from patients aged > or = 6 years were mostly susceptible to all antimicrobial agents tested. Overall, 23% of isolates showed reduced susceptibility to penicillin. Most (98.5%) isolates remained fully susceptible to cefotaxime, and a single isolate was resistant to quinolones.     

Simultaneous identification of 29 prevalent invasive pneumococcal serotypes or pairs of serotypes by hybridization-ligation PCR

A hybridization-ligation PCR assay was developed for the simultaneous detection and identification of 21 pneumococcal serotypes and 8 pairs of serotypes in the same serogroup: 1, 2, 3, 4, 5, 6A, 6B, 6C-6D, 7F-7A, 8, 9A-9V, 9N-9L, 11A, 14, 15B-15C, 16F, 17F, 18B-18C, 19A, 19F, 20, 21, 22A-22F, 23A, 23B, 23F, 28A-28F, 35B and 38. This novel assay was validated with 185 serotyped pneumococcal invasive clinical isolates and 57 culture-negative pleural fluids previously typed by real-time PCR.     

Invasive pneumococcal infections in Denmark from 1995 to 1999: epidemiology, serotypes, and resistance

Danish nationwide surveillance data on invasive pneumococcal disease from the 5-year period from 1995 to 1999, including 5,452 isolates, are presented and described. Annual overall incidence rates, serotype distribution, and antimicrobial susceptibility patterns of the isolates were monitored. Major changes in the total annual incidence rate from 27/100,000 in 1996 to 17/100,000 in 1999 and a significant change in the proportion of invasive isolates belonging to types 1 and 12F were observed. The serotype coverage rate by the 23-valent polysaccharide vaccine among the elderly was 92.9%, and the serotype coverage rate by the 7-, 9-, and 11-valent pneumococcal conjugate vaccines among children less than 2 years old were 71.7, 75.2, and 81.4%, respectively. Invasive isolates with reduced susceptibility to penicillin or erythromycin increased from 1995 to 1999, with a high proportion of the penicillin-nonsusceptible invasive isolates originating from people 60 years old or older (57.0%). These observations underline the importance of adequate surveillance systems of invasive pneumococcal disease to introduce and maintain national vaccine strategies and adequate antibiotic policy.     

Invasive Pneumococcal Infections in Denmark from 1995 to 1999: Epidemiology, Serotypes, and Resistance

Danish nationwide surveillance data on invasive pneumococcal disease from the 5-year period from 1995 to 1999, including 5,452 isolates, are presented and described. Annual overall incidence rates, serotype distribution, and antimicrobial susceptibility patterns of the isolates were monitored. Major changes in the total annual incidence rate from 27/100,000 in 1996 to 17/100,000 in 1999 and a significant change in the proportion of invasive isolates belonging to types 1 and 12F were observed. The serotype coverage rate by the 23-valent polysaccharide vaccine among the elderly was 92.9%, and the serotype coverage rate by the 7-, 9-, and 11-valent pneumococcal conjugate vaccines among children less than 2 years old were 71.7, 75.2, and 81.4%, respectively. Invasive isolates with reduced susceptibility to penicillin or erythromycin increased from 1995 to 1999, with a high proportion of the penicillin-nonsusceptible invasive isolates originating from people 60 years old or older (57.0%). These observations underline the importance of adequate surveillance systems of invasive pneumococcal disease to introduce and maintain national vaccine strategies and adequate antibiotic policy.     

Serotype-specific penicillin resistance of Streptococcus pneumoniae in Germany from 1992 to 2008

A total of 12,137 isolates from invasive pneumococcal disease was collected between January 1, 1992, and December 31, 2008, by the German National Reference Center for Streptococci (NRCS). Data on penicillin susceptibility were available for 11,814 isolates, whereat 8837 isolates (74.8%) were from adults, and 2977 isolates (25.2%) originated from children. Overall, the leading serotypes were serotypes 14 (16.5% of serotyped isolates), 3 (8.1%), 7F (7.7%), 1 (7.4%), and 23F (6.0%). The overall nonsusceptibility rate of all isolates adds up to 5.5% (intermediate, 4.3%; resistant, 1.2%) when the CLSI 2006 guidelines were applied, and to 1.4% (intermediate, 0.2%; resistant, 1.2%) when using the CLSI 2009 guidelines. Generally, slightly higher resistance rates were observed among children than among adults. Serotypes contributing considerably to pneumococcal penicillin nonsusceptibility by a combination of frequency among invasive isolates and relatively high penicillin nonsusceptibility are 19A, 9V, 6B, 19F, 23F, and 14. While the nonsusceptibility among serotype 19A isolates increased considerably over the years, the development of nonsusceptibility rates among the other serotypes is less and more ambiguous.     

Serotypes of carriage and invasive isolates of Streptococcus pneumoniae in Brazilian children in the era of pneumococcal vaccines

Nasopharyngeal carriage of Streptococcus pneumoniae is a key factor in the development of invasive disease and the spread of resistant strains within the community. A single nasopharyngeal swab was obtained from 648 unvaccinated children aged <5 years, either healthy or with acute respiratory tract infection or meningitis, during the winters of 2000 and 2001. The overall pneumococcal carriage rate was 35.8% (95% CI 32.1-39.6). The pneumococcal serotypes found most frequently in the nasopharynx were 14, 6B, 6A, 19F, 10A, 23F and 18C, which included five of the seven serotypes in the currently licensed seven-valent conjugate vaccine (PCV7); serotypes 4 and 9V were less common. Serotypes 1 and 5 were isolated rarely from the nasopharynx. A comparison of 222 nasopharyngeal isolates with 125 invasive isolates, matched for age and time to the carrier isolates, showed a similar prevalence of penicillin non-susceptible pneumococci (PNSp) (19.8% and 19.2%, respectively). PNSp serotypes were similar (6B, 14, 19F, 19 A, 23B and 23F) for carriage and invasive disease isolates. The coverage of PCV7 for carriage isolates (52.2%) and invasive isolates (62.4%) did not differ significantly (p 0.06); similarly, there was no significant difference in PCV7 coverage for carriage isolates (34.5%) and invasive isolates (28.2%) of PNSp. These data suggest that PCV7 has the potential to reduce pneumococcal carriage and the number of carriers of PNSp belonging to vaccine serotypes.     

Molecular epidemiology of pneumococcal carriage among children with upper respiratory tract infections in Hanoi,Vietnam

To investigate the molecular epidemiology of pneumococcal nasopharyngeal carriage in Hanoi, Vietnam, we studied 84 pneumococcal strains retrieved from children with upper respiratory tract infections. Serotypes 23F (32%), 19F (21%), 6B (13%), and 14 (10%) were found most often. A significant number of strains were antibiotic resistant. Fifty-two percent of the strains were (intermediate) resistant to penicillin, 87% were (intermediate) resistant to co-trimoxazole, 76% were resistant to tetracycline, 73% were resistant to erythromycin, and 39% were (intermediate) resistant to cefotaxime. Seventy-five percent were resistant to three or more classes of antibiotics. A high degree of genetic heterogeneity among the penicillin resistance genes was observed. In addition, the tetracycline resistance gene tet(M) and the erythromycin resistance gene erm(B) were predominantly observed among the isolates. Molecular analysis of the 84 isolates by restriction fragment end labeling (RFEL) revealed 35 distinct genotypes. Twelve of these genotypes represented a total of eight genetic clusters with 61 isolates (73%). The two largest clusters contained 24 and 12 isolates, and the isolates in those clusters were identical to the two internationally spreading multidrug-resistant clones Spain 23F-1 and Taiwan 19F-14, respectively. The remaining RFEL types were Vietnam specific, as they did not match the types in our reference collection of 193 distinct RFEL types from 16 countries. Furthermore, 57 of the 61 horizontally spreading isolates (93%) in the eight genetic clusters were covered by the seven-valent conjugate vaccine, whereas this vaccine covered only 43% of the isolates with unique genotypes. According to the serotype distribution of the nasopharyngeal pneumococcal isolates, this study suggests a high potential benefit of the seven-valent pneumococcal conjugate vaccine for children in Hanoi.     

Prevalence and patterns of resistance of Streptococcus pneumoniae strains isolated from carriers attending day care centers in the area of Athens

The prevalence and patterns of Streptococcus pneumoniae resistance to antibiotics was examined in 146 nasopharyngeal carrier strains obtained during April and May, 1997, from 382 healthy children attending eight day care centers (DCCs) in the area of Athens. Reduced susceptibility to at least one antibiotic was found in 32.6% as follows: penicillin 11.4% (intermediate), cefotaxime 0.8% (intermediate), trimethoprim-sulfamethoxazole 22.7%, erythromycin 13.6%, tetracycline 11.4%, chloramphenicol 8.3%. Most of the nonsusceptible to penicillin isolates belonged to serogroups 23, 9, and 19. Multidrug resistance was detected in 11.4% of S. pneumoniae isolates including five penicillin nonsusceptible serogroup 23 strains. More than half of the multidrug resistant strains were susceptible to penicillin and belonged to serogroups 6 (4), 23 (1), 19 (1), and 1(1). Strains that belonged to the same serogroup/serotype and had identical resistance patterns appeared to cluster in some DCCs. Antibiotic use in the previous month was associated with reduced susceptibility to penicillin (p = 0.007) and multidrug resistance (p = 0.012). In conclusion, a moderate prevalence of reduced susceptibility to penicillin in pneumococcal carrier strains was found in our community. Multidrug resistance was common and was often associated with susceptibility to penicillin. Several distinct patterns of resistance were observed, suggesting the spread of resistant clones to our country.     

Changes in epidemiology and antimicrobial susceptibility of nontyphoid Salmonella in children in southern Taiwan, 1997–2016

BackgroundThis study aimed to investigate the changing trends in serogroup distribution and antimicrobial susceptibility of nontyphoid Salmonella (NTS) isolated from children in the past two decades in Taiwan.MethodsThis retrospective study enrolled patients aged younger than 18 years with culture-proven NTS infection in a tertiary medical center from 1997 to 2016. Data on age, Salmonella serogroup, culture sample, and antimicrobial susceptibility were obtained from medical records. The rates of Salmonella serogroups and antimicrobial resistance were compared between period 1 (1997–2006) and period 2 (2007–2016).ResultsA total of 2075 NTS isolates were identified from 1997 to 2016 (1036 in period 1, 1039 in period 2). The major isolates were from feces (89.1%) and blood (10.4%). The most common serogroup was serogroup B (54.8%), followed by serogroup D (18.8%). There was a significant decline in the proportion of serogroup B with a concomitant rise in serogroup D in the past two decades. In period 2, resistance to cefotaxime and cefixime increased remarkably among serogroup B, whereas resistance to ampicillin increased notably among serogroup D. Furthermore, the incidence of multidrug-resistant (≥3 antibiotics) NTS significantly decreased in both serogroup B and serogroup D in period 2.ConclusionThis study revealed a significant rise in serogroup D with a concomitant decline in serogroup B NTS infection in Taiwanese children. Moreover, antimicrobial resistance to third-generation cephalosporins increased in serogroup B. Continuous surveillance of NTS serogroup distribution and antimicrobial susceptibility is mandatory to formulate therapeutic strategies for NTS infections.     

Antibiotic resistance in Streptococcus pneumoniae in six Latin American countries: 1993-1999 surveillance

The impact of invasive pneumococcal invasive disease is increased by the emergence of antibiotic resistance. We report regional and temporal variations in antibiotic resistance for 4,105 invasive Streptococcus pneumoniae isolates collected from Latin American children <5 years, between 1993 and 1999. Reduced susceptibility to penicillin was detected in 1,182 isolates (28.8%); 36% of these were resistant (> or = 2 microg/ml), including 12.6% with MIC > or = 4 microg/ml, occurring primarily in serotypes 14 and 23F. Reduced susceptibility to third-generation cephalosporins was detected in 12.1% of the collection. Mexico had the highest proportion of reduced susceptibility to penicillin (51.6%) and to third-generation cephalosporins (22%), whereas Brazil had the lowest at 20.9% and 0.7%, respectively. Isolates cultured from patients with pneumonia were more likely to have reduced susceptibility to third-generation cephalosporins than isolates from patients with meningitis (p < 0.0001). Susceptibility to trimethoprim-sulfamethoxazole, chloramphenicol, erythromycin, and vancomycin was tested by disk diffusion for 2.899 isolates. Reduced susceptibility was observed for 45.6%, 11.5%, 6.9%, and 0%, respectively. Thirty-one percent of the strains were resistant to > or = 2 drugs. High levels of antibiotic resistance in Latin America emphasize the need for the development of and adherence to rational antibiotic use guidelines. On-going surveillance will monitor the impact of these programs.     

Characteristics of the major etiologic agents of bacterial meningitis isolated in Poland in 1997-1998

Bacterial meningitis remains a major cause of morbidity and mortality worldwide, especially in children. In this paper, we present the results of the first two years (1997-98) of activity of the National Reference Centre for Bacterial Meningitis (NRCBM) on the etiologic agents of bacterial meningitis in Poland. Of the 220 isolates sent to the NRCBM, the most frequently identified was Neisseria meningitidis (n = 90, 40.9%), followed by Haemophilus influenzae (n = 58, 26.4%), and Streptoccus pneumoniae (n = 46, 20.9%). Of the meningococcal isolates, 88.9% belonged to serogroup B and 10.0% to serogroup C, and the most prevalent serotype was 22 (43.3%). Most meningococci were highly sensitive to penicillin; however, 10% of them had decreased susceptibility to penicillin. More than 90% of H. influenzae belonged to serotype b, and all were susceptible to third generation cephalosporins and chloramphenicol. A broad distribution of serotypes was found among pneumococcal isolates, of which the most common were serotypes 3 and 8. Penicillin nonsusceptible isolates constituted 13% of all pneumococcal isolates. Three of the resistant pnemococci belonged to serotype 23F. Data presented in this paper demonstrate the current epidemiological situation of bacterial meningitis in Poland.     

Distribution of capsular types and antibiotic susceptibility of invasive Streptococcus pneumoniae isolated from aborigines in central Australia.

Streptococcus pneumoniae strains isolated from 203 episodes of invasive disease in central Australian Aborigines were studied. Capsular types from children aged 0 to 4 years (n = 89) belonged most commonly to types 14, 6B, 9V, 4, 18C, and 19F, which together accounted for 67% of the pediatric strains. In adults (n = 98), types 1, 7F, 3, 4, 12F, and 8 contributed 68% of the isolates. Of 114 pneumococci from patients 5 years and older, 102 (89.5%) were types represented in the 23-valent pneumococcal polysaccharide vaccine. The MICs of five antibiotics were determined for 201 strains by using the E-Test (AB Biodisk). No chloramphenicol or ceftriaxone resistance was found, but 46 strains (22.9%) showed diminished susceptibility to one or more of the drugs penicillin, erythromycin, and trimethoprim-sulfamethoxazole. Penicillin resistance occurred in 15.4% of all isolates tested but only within the intermediate range (0.1 to 1.0 microgram/ml). Resistance to trimethoprimsulfamethoxazole affected 13.9% of the pneumococci tested. All type 23F and most type 19F organisms were resistant to one or more antibiotics. Resistance was significantly more common in pediatric isolates than in those from adults (chi 2(1) = 14.1; P < 0.001).     

Pre- and postvaccination clonal compositions of invasive pneumococcal serotypes for isolates collected in the United States in 1999, 2001, and 2002

Monitoring of serotypes and their clonal associations is critical as pneumococci adapt to the selective pressures exerted by the pneumococcal seven-valent conjugate vaccine (PCV7). We genotyped 1,476 invasive isolates from the Active Bacterial Core surveillance (705 [89.8%] of the isolates were obtained from children <5 years of age, and 771 [18.4%] of the isolates were obtained from individuals >5 years of age) in 2001 and 2002 (after the introduction of PCV7). The data were compared to the results for 1,168 invasive isolates (855 [83.9%] of the isolates were from children <5 years of age) collected in 1999. Among children <5 years of age, the incidence of invasive disease due to non-PCV7 serogroups together with serogroup 19A increased (P < 0.001). Eighty-three clonal sets, representing 177 multilocus sequence types (STs), were compiled from the 3-year isolate set. Among the non-PCV7 serogroups, newly emerging clones were uncommon; and a significant expansion of already established clones occurred for serotypes 3 (ST180), 7F (ST191), 15BCF (ST199), 19A (ST199), 22F (ST433), 33F (ST662), and 38 (ST393). However, additional minor clonal types within serotypes 1, 6A, 6B, 7C, 9N, 10A, 12F, 14, 15B/C, 17F, 19A, 19F, 20, 22F, and 33F that were absent in 1999 were found during 2001 and 2002. Although 23 clonal sets exhibited multiple serotypes, for most serotypes there were either no changes or modest changes in clonal compositions since the introduction of PCV7. The only example of an identical ST shared between non-PCV7 and PCV7 or PCV7-related serotypes was ST199; however, ST199 was prevalent within serotypes 15B/C and 19A before and after PCV7 introduction. Continued genotypic surveillance is warranted, since certain clones not targeted by PCV7 are expanding, and their emergence as significant pathogens could occur with maintained vaccine pressure.     

Implications of Streptococcus pneumoniae penicillin resistance and serotype distribution in Kuwait for disease treatment and prevention

Streptococcus pneumoniae causes serious infections. Treatment is difficult because of the emergence of penicillin resistance in S. pneumoniae. Pneumococcal vaccines offer the promise of control and prevention of pneumococcal infections. Serotype prevalence and penicillin susceptibility data for a country will predict the usefulness of the vaccines in that country. In Kuwait, the 23-valent polysaccharide and the 7-valent conjugate vaccines are being used without knowledge of the prevalent serotypes in the country. To obtain the necessary background information, data on penicillin susceptibility and serogroups were obtained from 397 consecutive clinical isolates collected during 2004 and 2005. Two hundred fifty-three isolates (64%) were penicillin resistant, and resistance was significantly higher in patients ≤15 years old and among the upper respiratory tract and eye isolates. The most common serotypes were 23F, 19F, 6A, 6B, 14, and 19A. Among the penicillin-resistant strains, the most common serotypes were 23F, 19F, 6B, 14, and 9A. Among the invasive strains, the most common serotypes were 14, 23F, 19A, and 9V. The polysaccharide vaccine gave 82% coverage against invasive infections in all age groups >2 years. The coverage of the 7-valent conjugate vaccine against invasive serotypes in children ≤2 years old was 55%. This moderate coverage by the conjugate vaccine against invasive infections in children necessitates a revised strategy on the use of the present conjugate vaccine and shows the need for formulation of an improved vaccine for superior coverage for Kuwait and possibly other countries of the Arabian Gulf.     

Reduction in pediatric invasive pneumococcal disease in the Basque Country and Navarre, Spain, after introduction of the heptavalent pneumococcal conjugate vaccine

This study evaluated the incidence of invasive pneumococcal disease, identified the causal serotypes, and tracked the evolution of the antibiotic susceptibility of Streptococcus pneumoniae isolates in the regions of the Basque Country and Navarre, Spain, before and after the introduction of the heptavalent pneumococcal conjugate vaccine. The study included all children aged between birth and 5 years diagnosed with bacteremia, meningitis, or bacteremic pneumonia caused by pneumococci. By the second year after introduction of the heptavalent pneumococcal conjugate vaccine, compared with the period 1998–2001, the incidence of invasive disease decreased by 64.3% in children less than 12 months of age, by 39.7% in children less than 24 months of age, and by 37.5% in children less than 60 months of age. The prevalence of clinical isolates of S. pneumoniae that lacked susceptibility to penicillin decreased by 58.2% among children less than 60 months of age. With an estimated coverage by four-dose heptavalent pneumococcal conjugate vaccine of 28–45% in 2003, the number of invasive pneumococcal infections in the Basque Country and in Navarre fell significantly after just 2 years of immunization, underscoring the importance of improving vaccination coverage under a universal childhood immunization program.     

Early Changes in the Serotype Distribution of Invasive Pneumococcal Isolates from Children after the Introduction of Extended-valent Pneumococcal Conjugate Vaccines in Korea, 2011-2013

This study was performed to measure early changes in the serotype distribution of pneumococci isolated from children with invasive disease during the 3-year period following the introduction of 10- and 13-valent pneumococcal conjugate vaccines (PCVs) in Korea. From January 2011 to December 2013 at 25 hospitals located throughout Korea, pneumococci were isolated among children who had invasive pneumococcal disease (IPD). Serotypes were determined using the Quellung reaction, and the change in serotype distribution was analyzed. Seventy-five cases of IPD were included. Eighty percent of patients were aged 3-59 months, and 32% had a comorbidity that increased the risk of pneumococcal infection. The most common serotypes were 19A (32.0%), 10A (8.0%), and 15C (6.7%). The PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, and 6A) accounted for 14.7% of the total isolates and the PCV13 minus PCV7 types (1, 3, 5, 7F and 19A) accounted for 32.0% of the total isolates. Serotype 19A was the only serotype in the PCV13 minus PCV7 group. The proportion of serotype 19A showed decreasing tendency from 37.5% in 2011 to 22.2% in 2013 (P = 0.309), while the proportion of non-PCV13 types showed increasing tendency from 45.8% in 2011 to 72.2% in 2013 (P = 0.108). Shortly after the introduction of extended-valent PCVs in Korea, serotype 19A continued to be the most common serotype causing IPD in children. Subsequently, the proportion of 19A decreased, and non-vaccine serotypes emerged as an important cause of IPD. The impact of extended-valent vaccines must be continuously monitored.     

Serotype distribution and antimicrobial resistance of invasive Streptococcus pneumoniae isolates among Croatian adults during a fifteen-year period (2005-2019)

AimTo assess serotype distribution, antibiotic resistance, and vaccine coverage against Streptococcus pneumoniae causing invasive infections in Croatian adults from 2005 to 2019.MethodsIn this retrospective study, invasive pneumococcal strains were collected through a microbiological laboratory network with country coverage >95%. Capsular typing was performed with the Quellung reaction. In vitro susceptibility testing was carried out according to the European Committee on Antimicrobial Susceptibility Testing guidelines. In macrolide-resistant isolates, the presence of ermB and mefA genes was evaluated.ResultsDuring the fifteen-year study period, 1123 invasive pneumococcal isolates were obtained. The most prevalent serotypes were 3, 14, 19A, 9V, 7F, and 23F, comprising 60% of all invasive pneumococcal isolates. Serotype 3 was the dominant serotype, with the highest prevalence in patients ≥65 years of age. Penicillin susceptibility, increased exposure was 18.6%, mostly associated with serotypes 14 and 19A. Resistance to penicillin was low (<1%). Macrolide resistance was 23%, mostly associated with serotypes 14, 19A, and 19F. The coverage with 13-valent conjugate vaccine (PCV13) and 23-valent polysaccharide vaccine (PPV23) was 80.2% and 93.6%, respectively.ConclusionsThe incidence of invasive pneumococcal disease in adults is highest in patients ≥65 years of age. Penicillin susceptibility, increased exposure and macrolide resistance were mostly associated with serotypes 14 and 19A. PCV13 and PPV23 provide very high serotype coverage. Future studies should evaluate the effects of the 10-valent vaccine, introduced in the Croatian National Immunization Program in June 2019, on serotype distribution and antibiotic resistance rates.

Streptococcus pneumoniae is among the most concerning human pathogens, with high morbidity and mortality rates worldwide. Pneumococcal infections range from non-invasive mucosal diseases (including acute otitis media, acute sinusitis, and pneumonia) to invasive, life-threatening infections (such as meningitis, sepsis, and bacteremic pneumonia) (1). Invasive pneumococcal disease (IPD) mostly affects children younger than 5 years and patients ≥65 years old (2). Every year, 500 000 children under 5 years of age die of IPD (3). Both morbidity and mortality rates are higher in developing countries (3). Community-acquired pneumonia is the most common pneumococcal disease worldwide, being responsible for more than 1.5 million of deaths annually. A significant fraction of these deaths are caused by Streptococcus pneumoniae (4,5).Antimicrobial resistance of Streptococcus pneumoniae is a growing global health problem, mostly affecting penicillin and macrolides. The patterns of antimicrobial susceptibility differ among serotypes and geographic regions (6). Penicillin resistance has emerged within a few decades after penicillin introduction and has spread worldwide (7). The prevalence of antibiotic-resistant Streptococcus pneumoniae has been increasing (8,9). In Europe, the resistance rate in France, Spain, and Eastern European countries is concerning (10). Worldwide, some regions, such as South Africa, have antibiotic non-susceptibility rates of up to 79% (11). However, in the past several years some countries have reported decreased resistance rates (12-15).Macrolide resistance is commonly present among invasive and non-invasive Streptococcus pneumoniae isolates. The main mechanisms are drug efflux system encoded by mef genes (M phenotype) and target modification mainly due to ermB genes, (MLS_B phenotype) (16,17).The new fluoroquinolones or respiratory quinolones (levofloxacin, gatifloxacin, and moxifloxacin) have enhanced in vitro activity against Streptococcus pneumoniae and are used to treat respiratory tract infections in adults. Increasing resistance to fluoroquinolones has been reported in Asia and Africa (18,19). In addition, ineffectiveness of fluoroquinolones in the treatment of pneumococcal infections is associated with acquired resistance of Streptococcus pneumoniae to this group of antibiotics (20,21).Increased resistance of Streptococcus pneumoniae to routinely used antibiotics warrants pneumococcal vaccine introduction as a tool for IPD prevention. In Europe, two pneumococcal vaccines are registered for use in adults: a 13-valent pneumococcal conjugate vaccine (PCV13, including serotypes 4, 6B, 9V, 14, 18C, 19F, 23F, 1, 5, 7F, 3, 6A, and 19A) and a 23-valent pneumococcal polysaccharide vaccine (PPV23, including PCV13 serotypes plus 1, 2, 5, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, and 33F) (22,23). In June 2019, a 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in the Croatian National Immunization Program (NIP) for children only (scheme: 8 weeks – 16 weeks – 12 months) (24). In January 2021, the Croatian Public Health Institute revised its recommendations for pneumococcal vaccination of adults. Immunocompetent adults are now advised to be vaccinated with PPV23 only, while immunocompromised and asplenic patients are recommended to receive both vaccines, starting with PCV13 as the first dose (25). The aim of this study was to analyze the serotype distribution and antibiotic resistance of invasive Streptococcus pneumoniae isolates before the introduction of PCV10 in the childhood vaccination schedule, together with the coverage of currently available vaccines (PCV13 and PPV23). This study is the first and the most comprehensive so far in Croatia, analyzing invasive pneumococcal isolates collected during 15 consecutive years. These data will help us assess the impact of different vaccines in the IPD prevention among adults, especially those ≥65 years old.     

Carriage and invasive isolates of <Emphasis Type="Italic">Streptococcus pneumoniae</Emphasis> in Caracas,Venezuela: the relative invasiveness of serotypes and vaccine coverage

The introduction of a pneumococcal conjugate vaccine in Venezuela needs previous studies to assess vaccine efficiency. We conducted a survey of nasopharyngeal pneumococcal carriage in urban children in Caracas and studied the distribution of serotypes. We compared these data with survey data available for invasive strains isolated in the same area and in the same time period. An overall pneumococcal carriage rate of 27% was observed. The most predominant capsular serotypes among carriage isolates were 6B (29%), 19A (13.8%), 23F (10%), 14 (8.3%), 6A (8.3%) and 15B/C (3.3%) and among invasive isolates 6B (25%), 14 (15%), and 19A, 6A, 7F, and 18 (7.5% each). The serotypes/groups 1, 5, 7F and 18, jointly covering 30% of the invasive strains, represented less than 0.7% of the carrier strains. The theoretical coverage of the pneumococcal conjugate vaccine PCV13 for carriage and invasive strains was calculated to be 74% and 90%, respectively. Our study demonstrates important differences for the serotype distribution in disease and carriage isolates and provides a key baseline for future studies addressing the prevalence and replacement of invasive and carriage serotypes after the introduction of the PCV 13 vaccine in Venezuela in the year 2010.     

Serotyping and antibiotic resistance of Streptococcus pneumoniae isolated from pediatric infections in central Greece

Objective: To determine the distribution of serogroups/serotypes and antibiotic resistance pattern of Streptococcus pneumoniae isolated from pediatric infections in central Greece.
Methods: In total, 306 S. pneumoniae strains isolated from children, aged from 18 days to 14 years (median 18 months), during a 21-month period, from different specimen sources, were studied. Susceptibility testing was carried out by the Kirby-Bauer method and by the Etest, and serotyping by the Quellung reaction.
Results: Of the S. pneumoniae isolates, 3.9% were highly resistant to penicillin (PR), while 17.6% were intermediately resistant (IPR). PR and IPR isolates were found to be, in general, more resistant to other antibiotics than penicillin-susceptible isolates. The PR and IPR isolates belonged to the serogroup/serotypes 19, 23, 9, 6 and 14 (in descending order of frequency). The penicillin-susceptible isolates belonged to 20 different groups/serotypes, the most common being 19, 6, 14, 9, 3, 23 and 1 (in descending order of frequency). Serogroup 23 was often found to be multiresistant.
Conclusions: Resistance to penicillin in S. pneumoniae isolates is relatively low and differs according to the specimen type. All the pneumococcal serogroups/serotypes isolated from the children were found to be included in the 23-valent polysaccharide vaccine. Most of the children with a pneumococcal infection, however, were less than 2 years old and could not be protected by the existing vaccine.     

Meningococcal infections in the Province of Québec, Canada, during the period 1991 to 1992.

A total of 234 strains of Neisseria meningitidis obtained from hospitalized patients living in the province of Québec during the period 1991 to 1992 were characterized according to their serogroup, serotype, subtype, electrophoretic type, and antimicrobial susceptibility. All these strains were recovered from sterile body fluids, except for one strain that was isolated postmortem from a cutaneous lesion. For both years, serogroup C was the most prevalent (69.7%), followed by serogroup B (27.4%). Serotype 2a represented 80.3% of serogroup C isolates, and P1.2 was the most common subtype associated with this serotype. Clone ET 15 accounted for 76.5% of serogroup C isolates and 90.0% of serotype 2a strains. Although meningococcal disease occurred mostly in children under the age of 5 (9.7 cases per 100,000 children), with a peak incidence for children under 1 (20.3 cases per 100,000 children), most fatalities occurred among teenagers (12 to 19 years old). The total fatality rate was 11.5%, and serogroup C strains were responsible for 88.9% of these fatalities. Thirteen strains had a reduced susceptibility to penicillin G, and 28 strains were resistant to sulfadiazine. One strain was resistant to both rifampin and sulfadiazine and showed a reduced susceptibility to penicillin G.