Characteristics of Haemophilus influenzae Isolates Responsible for Invasive Infections in Poland in 2018-2023.

Haemophilus influenzae is an important cause of morbidity and mortality from pneumonia, meningitis and other invasive infections among infants and young children in developing countries. Virtually all episodes of H. influenzae meningitis and most episodes of severe H. influenzae pneumonia are caused by serotype b (Hib), and these 2 entities together are estimated to cause >375 000 deaths annually in children <5 years old.1, 2 Invasive diseases caused by Hib now can be prevented by immunization with polysaccharide-protein conjugate vaccines that were developed in the 1980s and have proved to be safe, immunogenic and highly effective when given to infants.3 In the industrialized countries Hib meningitis and other invasive Hib diseases have been virtually eliminated through widespread use of the vaccines.4, 5 Until now, however, the vaccines have not been added to the routine immunization schedules of developing countries. The aims of this article are to review the epidemiology and burden of Hib disease among infants and young children, especially in developing countries, describe the status of Hib conjugate vaccines, identify factors that will affect the introduction and routine use of Hib conjugate vaccines in developing countries and recommend priority actions to facilitate such use. BURDEN OF HIB DISEASE Strains of H. influenzae are either encapsulated or nonencapsulated. The encapsulated strains are differentiated into six serotypes (a through f) based on the antigenic structure of the capsular polysaccharide; nonencapsulated strains are classified as nontypable. Although all serotypes of H. influenzae and the nonencapsulated strains may cause invasive disease, Hib is responsible for most episodes of severe disease among children <5 years of age. Hib pneumonia.Diagnostic methods. Efforts to define the burden of morbidity and mortality resulting from Hib pneumonia have been hindered by a lack of sensitive and specific tests to determine the etiology of pneumonia. Problems in the use of culture depend on the type of specimen being evaluated. Culture of fluid aspirated from the lung is sensitive and specific, but lung aspirates are performed rarely, may be dangerous and can be done only in hospitalized children with lobar disease. Blood cultures are more widely available and are highly specific but are insensitive. Secretions from the lower respiratory tract are difficult to obtain from children and often are contaminated with upper respiratory tract flora, making interpretation of culture results difficult. Nasopharyngeal (NP) swab specimens are easy to obtain, but there is no evidence that culture results reliably predict the etiology of pneumonia. The sensitivity of tests to detect Hib capsular antigen from urine or cerebrospinal fluid has varied between studies but frequently has been <50% for culture-documented invasive infection. Specificity also may be reduced by upper respiratory carriage of Hib, which may cause positive antigen assays in urine samples. Attempts to detect Hib infection by detecting antibody responses to the type b capsular antigen have been reported from several developing countries,6-8 but the sensitivity and specificity of this method are unknown. The practical value of this approach also is limited by difficulties in obtaining acute and convalescent sera from young children. These difficulties also limit the use of culture, antigen detection and serologic methods for diagnosing other causes of pneumonia. Nevertheless studies that use a combination of culture and nonculture methods have identified a bacterial or viral pathogen in one-fourth to three-fourths of children with pneumonia, with higher yields of bacteria in children with severe disease.6-8 Multiple pathogens are identified in almost one-third of thoroughly studied cases, which may reflect poor specificity of the tests or the occurrence of true mixed infections. When evidence of infection with Hib and a viral pathogen is obtained, it is possible that the viral respiratory infection occurred first and facilitated secondary invasion of the lower respiratory tract by Hib. When death results from mixed infection, however, it is likely that the bacterial agent is largely responsible. This conclusion is based in part on the more frequent isolation of bacteria from children with severe disease and on evidence that providing antimicrobials early to children with pneumonia substantially reduces their risk of death. Role of Hib in pneumonia. Because the etiology of most episodes of pneumonia cannot be determined, models have been developed to estimate the contribution of specific pathogens to the total burden of pneumonia morbidity and mortality. One approach has been to assume that results from lung aspirate studies apply to all pneumonias.9 This is probably inappropriate, however, because aspirates are performed only on children with lobar pneumonia, a syndrome caused predominantly by bacterial infection, whereas viruses play a more important role in causing nonlobar pneumonia, especially episodes that are not clinically severe. Another approach, used in this review, is to estimate the contribution of specific etiologic agents by characterizing the overall burden of pneumonia and its age distribution, categorizing infection and mortality as bacterial or viral and apportioning cases and deaths in each group based on the relative frequency of different pathogens as determined by review of the available literature. Because serotyping of H. influenzae isolates is not reported in all studies and because of the likelihood that bacteremic disease may differ for type b and other H. influenzae infections, calculations first estimate pneumonia deaths caused by all H. influenzae types, after which the contribution of type b is determined. By this method all H. influenzae (including all serotypes and nontypable strains) are estimated to cause 482 000 pneumonia deaths each year among children <5 years old in the developing world, which is 16% of all pneumonia deaths not associated with measles or pertussis. Although 67% of these deaths occur in infants, only ∼5% occur at <2 months of age, when maternal antibodies protect most infants. Morbidity from H. influenzae pneumonia also is more common among infants, but the age shift is less marked than for deaths, because of the higher case fatality rate in the very young. Sequelae from pneumonia are estimated to occur in ∼1% of cases, bronchiectasis and reactive airway disease being most common. The proportions of H. influenzae pneumonia cases and deaths caused by Hib are not precisely defined. The proportion of cases caused by Hib can be estimated from studies with cultures of fluid obtained by lung puncture in children with lobar pneumonia. In three such studies Hib accounted for a trimmed mean of 35% of all H. influenzae pneumonias (range, 16 to 63%). In contrast the proportion of Hib was 71% (trimmed mean; range, 29 to 100%) in eight studies based on isolates from children with bacteremic H. influenzae pneumonia. These data suggest that most nonbacteremic cases of H. influenzae pneumonia are caused by strains other than Hib, whereas most cases of bacteremic H. influenzae pneumonia are caused by Hib. For all H. influenzae irrespective of serotype, pneumonia probably is caused by descending infection from the upper respiratory tract. Once they reach the lung, however, Hib organisms are more likely to cause bacteremia, probably because the type b capsule protects the organism from phagocytosis. There are no data from industrialized or developing countries on the proportion of deaths among all H. influenzae pneumonias that is caused by Hib. It may be reasonable to assume, however, that this proportion is similar to the proportion of Hib among bacteremic pneumonias, in which the risk of death is known to be highest. This would suggest that about 71% of deaths among children <5 from H. influenzae pneumonia, or 342 000 annual pneumonia deaths in the developing world, are caused by Hib. The above estimates are for the entire developing world and differences between countries are likely. It is reported, for example, that the proportion of all deaths caused by pneumonia (and probably also by Hib pneumonia) is greatest in countries with the highest rates of infant mortality.10 It also is believed that in countries with lower infant mortality rates and better standards of living, viruses are a relatively more frequent cause of pneumonia than are bacteria, including Hib. Hib meningitis. About 200 000 cases and 37 000 deaths occur annually from H. influenzae meningitis among children <5 years of age in developing countries.2 Most studies show that >97% of H. influenzae meningitis is caused by Hib.11-13 Two exceptions are reports from Papua New Guinea14 and the White Mountain Apaches,15 where 78 to 82% of H. influenzae meningitis was caused by Hib. Incidence in industrialized countries.Table 1 summarizes the rates of Hib meningitis from 13 studies in industrialized countries. Before the use of Hib vaccines the reported incidences among children <5 years old of Hib meningitis and of all invasive Hib diseases were 8 to 60 (median, 25) and 21 to 100 (median, 41) cases per 100 000 per year, respectively. The decision to use Hib vaccines routinely in these countries was based on these data.TABLE 1: Reported incidence of Hib meningitis and invasive Hib disease among children <5 years old in industrialized countries before the widespread use of Hib vaccines Incidence in developing countries. Available data are summarized in Table 2 and median disease rates by region are shown in Figure 1. These vary widely, from a median of 109 cases per 100 000 children <5 years in the Western Pacific and Oceania, to 6 per 100 000 children in Asia. Variations usually were smaller within than between regions. In South America and the Middle East incidence varied from 17 to 25 and 16 to 31 cases per 100 000 children, whereas in Africa it was 50 to 60 cases per 100 000 per year. The incidences in Hong Kong and Malaysia were similar and substantially lower than elsewhere. In the Western Pacific the incidence appeared to vary, being substantially higher in New Caledonia and Vanuatu than Fiji.TABLE 2: Reported incidence of Hib meningitis and invasive Hib disease among children <5 years old in low and middle income countries, by geographic region Fig. 1: Geographic variations in the median reported incidence of Hib or H. influenzae meningitis among children <5 years old, by region.No estimates of incidence are available from India or China (apart from the reports in this supplement) or from the newly independent states of the former Soviet Union. In the Middle East and South America, data are available only from wealthier countries; estimates of incidence in lower income countries of these regions are needed. In Africa the only incidence estimates are from the neighboring West African countries Senegal, The Gambia and Niger and from South Africa. Although hospital-based studies have shown that Hib is a common cause of bacterial meningitis in Central and East Africa, data on incidence are lacking. Incidence in native Americans. Navajo and Apache Indians and Native Alaskans have the highest reported incidence of Hib meningitis and other invasive Hib diseases.15, 29, 43 The incidence of Hib meningitis is 152 to 282 cases per 100 000 children <5 years old. Geographic and population differences in the reported incidence of Hib meningitis are unexplained. Possible explanations include the sensitivity of diagnostic methods, the proportion of patients given antibiotics before admission, socioeconomic and environmental conditions and genetic factors. The latter almost certainly play a role in the high incidence observed in American Indians and Native Alaskans. Isolation of H. influenzae is not difficult but does require the use of appropriate culture media. Because many of the reported studies do not indicate the type of media and reagents used, it is not possible to assess the effect of diagnostic technique on reported incidence. Assessing the independent effects of socioeconomic or environmental conditions and genetic factors on the incidence of Hib meningitis is difficult. For example the incidence of Hib meningitis among Melanesians in New Caledonia is substantially greater than that among Caucasian residents (70 vs. 10 cases per 100 000 children <5 years old).36 However, the socioeconomic level of the Melanesians is lower than that of the Caucasians, making it impossible to distinguish the relative importance of genetic or environmental and socioeconomic factors, such as crowding. Age distribution of Hib meningitis. In developing countries the incidence of Hib meningitis typically peaks earlier than in industrialized countries. Figure 2 illustrates this point with data from The Gambia, the United States and Finland.20, 44, 46 In the Gambia 45% of cases occurred in the first 6 months of life and 83% by age 1 year. By contrast in Finland, only 5% of cases occurred among infants <6 months old and only 35% by age 1 year. The US showed an intermediate pattern.Fig. 2: Cumulative proportion of H. influenzae meningitis cases, by age, from The Gambia, United States and Finland. Data adapted from References 20, 45 and 46.The earlier peak of meningitis in developing areas might reduce the benefit of immunization, because infants are not fully immunized before 4 to 6 months of age. It is possible, however, that herd immunity would minimize this problem. By eliminating carriage of Hib immunization could reduce the incidence of meningitis in all ages, including those not yet fully immunized. In the US widespread use of Hib vaccine caused a 40% reduction in the incidence of meningitis in unimmunized infants <2 months old.4 Mortality resulting from Hib meningitis. The case fatality rate (CFR) for Hib meningitis also varies among countries, with rates in some up to 40%.11, 12 In general the CFR for bacterial meningitis varies inversely with measures of health status or development, with countries with higher per capita health expenditures having a lower CFR. Long term disability after Hib meningitis is common, even where the CFR is low. Up to 30% of survivors develop sequelae that range in severity from mild hearing loss to severe neurologic damage and mental retardation. In poor countries up to 20% of these children die within 4 months after the episode of meningitis.47 Other invasive Hib disease. In industrialized countries meningitis accounts for 40 to 60% of all invasive Hib disease. Other invasive diseases caused by Hib, in addition to bacteremic pneumonia and meningitis, include cellulitis, septic arthritis and, among children >2 years, epiglottitis. The incidence of all invasive Hib disease in various developed countries is summarized in Table 1. Few data exist on the incidence of these syndromes in developing countries. EPIDEMIOLOGY OF HIB DISEASE Spread of infection. Hib is pathogenic only for humans; no animal reservoir exists. Transmission of Hib occurs by spread of respiratory droplets from infected to susceptible persons. Infection typically is established in the oropharynx. This can lead to asymptomatic oropharyngeal carriage, which may persist for months. Invasive disease occurs in a small fraction of infected persons. The reported prevalence of oropharyngeal carriage of Hib varies from country to country. In industrialized countries carriage rates range from 1 to 4%. In developing countries where fewer data are available, carriage rates are sometimes much higher, e.g. 33% in one study from The Gambia.48 Available studies are summarized in Table 3.48-55TABLE 3: Prevalence of oropharyngeal Hib carriage before vaccination in industrialized and developing countries Carriage of Hib is correlated closely with age and the incidence of Hib disease. In industrialized countries carriage is rare in the first year of life and reaches a peak incidence of 3 to 5% during the preschool and school age years.11 Where the peak incidence of Hib disease occurs earlier, as among Navajo Indians, substantial carriage of Hib (prevalence rates of about 3%) occurs as early as 3 months of age.56 Risk factors for Hib infection.Environmental factors. Hib infection is acquired through close contact with a person who is an asymptomatic carrier of Hib or has invasive Hib disease. Most transmission occurs through contact with carriers because they are much more numerous than persons with invasive Hib disease. Risk factors for Hib carriage or disease include an increased number of siblings in a household,57 crowded living conditions,45 day-care attendance45, 57-59 and close contact with a patient with invasive Hib disease.49, 60 Viral upper respiratory tract infections may enhance transmission of Hib by increasing production and spread of respiratory secretions. Exposure to smoke61 and other respiratory irritants may enhance colonization with Hib and increase the risk of developing invasive disease after colonization.58 Host factors. The risk of invasive disease after colonization is related to an individual's level of immunity to Hib, as measured by serum antibodies directed against the capsular polysaccharide. The prevalence of antibody to Hib is high in newborns, as are mean serum titers, owing to passively transferred maternal antibody. Antibodies reach a nadir by age 3 to 4 months and then increase steadily during early childhood as a result of natural exposure to Hib or other organisms with cross-reacting antigens. The incidence of Hib disease shows a reciprocal pattern, being low in newborns, reaching a peak in midinfancy or early childhood and then declining as antibody titers rise.62 The risk of invasive Hib disease is increased in patients with a variety of hematologic and immunologic disorders, including sickle-cell anemia, asplenia, antibody deficiency syndromes, complement deficiencies and malignancies (particularly during chemotherapy).63 American adults with HIV infection have a moderately increased rate of invasive H. influenzae disease (both typable and nontypable), but the full effect of HIV infection on rates of Hib disease is not yet clear.64 Although many studies report equivalent rates for Hib disease in boys and girls, several have reported a 20 to 50% increased incidence among boys.63 There also are variations in the incidence of Hib meningitis across populations that do not seem to be explained by differences in socioeconomic conditions alone, suggesting that genetic factors also may affect susceptibility to invasive Hib disease. For example the incidence of Hib meningitis among Chinese children living in Hong Kong is 10 to 20 times lower34 than that observed in US and European populations. CONTROL OF MORTALITY BY CASE MANAGEMENT The diagnosis of pneumonia in children with cough or difficult breathing can be made using easily discernible signs. Pneumonia cases are classified according to severity and empiric antimicrobial therapy is given.65 The antimicrobials recommended for outpatients (trimethoprim-sulfamethoxazole, amoxicillin and procaine penicillin) and inpatients (penicillin, chloramphenicol) are effective against sensitive strains of S. pneumoniae and H. influenzae. This approach has decreased mortality caused by acute lower respiratory infections, as well as total childhood mortality, in multiple intervention trials.66 A recent metaanalysis of six intervention trials concluded that pneumonia case management interventions can reduce mortality among children <5 years of age by 20 to 25%. The effectiveness of this approach has made case management the key strategy of national acute respiratory infection control programs. Despite its proven effectiveness global implementation of case management is constrained by the need to train and supervise numerous health workers, ensure the availability of recommended antimicrobials and educate mothers on appropriate care-seeking for children with respiratory illness. Moreover antimicrobial resistance, which is increasing rapidly in many countries, may reduce the efficacy of empiric antimicrobial therapy. For example surveillance in Pakistan found that more than one-half of H. influenzae isolated from blood in children with pneumonia had decreased susceptibility to trimethoprim-sulfamethoxazole,67 the treatment recommended by the National ARI Control Program. Studies in other countries (Thailand, Central African Republic) also found resistance to this antimicrobial, but at lower rates. Hib strains also have developed resistance to beta-lactam antibiotics, such as penicillin and amoxicillin, most often by production of beta-lactamase, but sometimes through alterations in penicillin-binding proteins. Rates of beta-lactam resistance in developing countries generally have been lower than in developed countries, where use of this class of agents is more common. Increasing resistance is likely in developing countries, however, owing to the wide availability and indiscriminate use of antimicrobials. PREVENTION OF HIB DISEASE Breast-feeding. Breast-feeding provides >90% protection from invasive Hib disease in infants <6 months of age,45 probably reflecting a protective effect of breast milk antibodies on NP colonization by Hib. Antimicrobial prophylaxis. Antimicrobial treatment can eradicate oropharyngeal carriage of Hib organisms. In the US and elsewhere rifampin (20 mg/kg orally once daily for 4 has been used to secondary cases among close of children with invasive Hib disease. The protective role of passively transferred maternal antibodies is with also provides up to 4 months of protection against invasive Hib disease in high risk In a among Apache infants, immunization with bacterial at 6 and 10 months protection against invasive Hib disease for 3 months and protection for 4 It also showed that one of a serum of for up to 4 In addition of and conjugate Haemophilus influenzae type b vaccine higher titers between the first and of and not with responses to the and of to the routine use of are high and the risk of with blood antibodies to were protective against invasive Hib disease was first by the observed between the incidence of Hib meningitis and the prevalence of serum antibodies to incidence of Hib meningitis as the prevalence of antibodies The protective role of was by the studies of immunization with These to against Hib disease by antibodies to the capsular an Hib vaccine high of immunization protection be and the vaccine be effective when given to young infants. The first of Hib vaccines of The efficacy of one vaccine was in children 3 to Two of vaccine of protection for children months old but not protect children months old. results protective of children months old had of in only 10 to of those months this level of antibody. In addition the antibodies by children months were of the whereas children months and A different vaccine was among children to months old in the of vaccine efficacy from to but most were on the of vaccines children months old but were immunogenic in children months of Moreover they not asymptomatic carriage of The poor of in young infants is of most of which are The to reliably to is not established the year of These results to to develop Hib vaccines that would be immunogenic and in young infants. This was by the to a carrier a The vaccine was immunogenic in infants, a by and antibody and evidence of immunologic The with Hib conjugate vaccines is HIB and use. Hib conjugate vaccines have been each of to a The vaccines differ in carrier the method of the carrier and and the and of in each Table 4 summarizes the of these vaccines, reduced vaccines and are all or being Hib conjugate vaccines Hib conjugate vaccines now are given routinely to infants in most industrialized countries in Western America, and the Western In several countries this has to the of invasive Hib In the US the for is whereas for and three are all are given with and and vaccine is not recommended for infants in the US because of poor in this age In the developing world Hib conjugate vaccine often is available through the and a number of countries have added or are Hib conjugate vaccines to their on programs. Hib conjugate vaccines sometimes can be given in the with vaccine and can of be given as a but are not more common when the vaccines are given by either method than when vaccine is given for Hib antibodies either antibody or the of antibody to assays and serum These assays are relatively and difficult to For these they have not been used routinely to all sera in vaccine assays include the and results as of of measures antibody that It is the for Hib antibody were by the US and for of Hib conjugate vaccines in the of the include the need to with and its to or which also measures is does not require and can antibody to different and Efforts have been made to the for results from different can be or of antibody. The risk of invasive Hib disease is inversely related to the level of serum antibodies to The protective of however, has not been of the protective of serum have been based on animal of acquired studies of and immunization Two serum and are used as of and term respectively. The of for term protection is based on and protection studies antibody titers above this level in In contrast studies with vaccine were used to define the for term It may be reasonable to use a lower for Hib conjugate vaccines, however, because they antibodies of higher and greater In addition because conjugate vaccines it is possible that only low of antibody are for protection and that the level of antibody shows well an has been In studies of Hib conjugate vaccines, three measures are the mean of the proportion of infants with an and the proportion of infants with an to Hib conjugate Hib conjugate

Global Pneumococcal Disease and Policies for Control

Invasive Haemophilus influenzae (Hi) disease has decreased in countries that included Hi type b (Hib) vaccination in their childhood immunization programs in the 1990s. Non-typeable (NT) and non-b strains are now the leading causes of invasive Hi disease in Europe, with most cases reported in young children and the elderly. Concerningly, no vaccines toward such strains are available and beta-lactam resistance is increasing. We describe the epidemiology of invasive Hi disease reported to the Norwegian Surveillance System for Communicable Diseases (MSIS) (2017–2021, n = 407). Whole-genome sequencing (WGS) was performed on 245 isolates. We investigated the molecular epidemiology (core genome phylogeny) and the presence of antibiotic resistance markers (including chromosomal mutations associated with beta-lactam or quinolone resistance). For isolates characterized with both WGS and phenotypic antibiotic susceptibility testing (AST) (n = 113) we assessed correlation between resistance markers and susceptibility categorization by calculation of sensitivity, specificity, and predictive values. Incidence rates of invasive Hi disease in Norway ranged from 0.7 to 2.3 per 100,000 inhabitants/year (mean 1.5 per 100,000) and declined during the COVID-19 pandemic. The bacterial population consisted of two major phylogenetic groups with subclustering by serotype and multi-locus sequence type (ST). NTHi accounted for 71.8% (176). The distribution of STs was in line with previous European reports. We identified 13 clusters, including four encapsulated and three previously described international NTHi clones with blaTEM–1 (ST103) or altered PBP3 (rPBP3) (ST14/IIA and ST367/IIA). Resistance markers were detected in 25.3% (62/245) of the isolates, with blaTEM–1 (31, 50.0%) and rPBP3 (28, 45.2%) being the most frequent. All isolates categorized as resistant to aminopenicillins, tetracycline or chloramphenicol possessed relevant resistance markers, and the absence of relevant substitutions in PBP3 and GyrA/ParC predicted susceptibility to cefotaxime, ceftriaxone, meropenem and quinolones. Among the 132 WGS-only isolates, one isolate had PBP3 substitutions associated with resistance to third-generation cephalosporins, and one isolate had GyrA/ParC alterations associated with quinolone resistance. The detection of international virulent and resistant NTHi clones underlines the need for a global molecular surveillance system. WGS is a useful supplement to AST and should be performed on all invasive isolates.

Severe meningococcal disease in childhood

Prospective epidemiologic surveillance of invasive pneumococcal disease and pneumonia in children in San José, Costa Rica

Objectives: To determine the serotype distribution of pneumococcus causing invasive pneumococcal disease (meningitidis, bacteremia and empyema) in children in Turkey, and to observe potential changes in this distribution in time to guide effective vaccine strategies. Methods: We surveyed S. pneumoniae with conventional bacteriological techniques and with real-time polymerase chain reaction (RT-PCR) in samples of cerebrospinal fluid (CSF), blood and pleural fluid. S. pneumoniae strains were isolated from 33 different hospitals in Turkey, which are giving health services to approximately 60% of the Turkish population. Results: A total of 167 cases were diagnosed with invasive pneumococcal disease between 2015 and 2018. We diagnosed 52 (31.1%) patients with meningitis, 104 (62.2%) patients with bacteremia, and 11 (6.6%) patients with empyema. Thirty-three percent of them were less than 2 years old and 56% less than 5 years old. Overall PCV13 serotypes accounted for 56.2% (94/167). The most common serotypes were 19 F (11.9%), 1 (10.7%) and 3 (10.1%). Conclusions: Besides the increasing frequency of non-vaccine serotypes, vaccine serotypes continue to be a problem for Turkey despite routine and high-rate vaccination with PCV13 and significant reduction reported for the incidence of IPD in young children. Since new candidate pneumococcal conjugate vaccines with more serotype antigens are being developed, continuing IPD surveillance is a significant source of information for decision-making processes on pneumococcal vaccination.

Haemophilus influenzae type b vaccination

Background. Invasive bacterial diseases cause significant disease and death in sub-Saharan Africa. Several are vaccine preventable, although the impact of new vaccines and vaccine policies on disease patterns in these communities is poorly understood owing to limited surveillance data.Methods. We conducted a hospital-based surveillance of invasive bacterial diseases in The Gambia where blood and cerebrospinal fluid (CSF) samples of hospitalized participants were processed. Three surveillance periods were defined in relation to the introduction of pneumococcal conjugate vaccines (PCVs), before (2005- 2009), during (2010–2011) and after (2012–2015) PCV introduction. We determined the prevalences of commonly isolated bacteria and compared them between the different surveillance periods.Results. A total of 14 715 blood and 1103 CSF samples were collected over 11 years; overall, 1045 clinically significant organisms were isolated from 957 patients (972 organisms [6.6%] from blood and 73 [6.6%] from CSF). The most common blood culture isolates were Streptococcus pneumoniae (24.9%), Staphylococcus aureus (22.0%), Escherichia coli (10.9%), and nontyphoidal Salmonella (10.0%). Between the pre-PCV and post-PCV eras, the prevalence of S. pneumoniae bacteremia dropped across all age groups (from 32.4% to 16.5%; odds ratio, 0.41; 95% confidence interval, .29–.58) while S. aureus increased in prevalence, becoming the most prevalent bacteria (from 16.9% to 27.2%; 1.75; 1.26–2.44). Overall, S. pneumoniae (53.4%), Neisseria meningitidis (13.7%), and Haemophilus influenzae (12.3%) were the predominant isolates from CSF. Antimicrobial resistance to common antibiotics was low.Conclusions. Our findings demonstrate that surveillance data on the predominant pathogens associated with invasive disease is necessary to inform vaccine priorities and appropriate management of patients.

Penicillin resistance in Streptococcus pneumoniae in Istanbul, Turkey

Haemophilus influenzae is a human-specific pathogen responsible for respiratory tract infections, meningitis, and sepsis. The study aimed to characterize antibiotic resistance in H. influenzae strains isolated from patients with lower respiratory tract infections over 15years in Poland. The minimuminhibitory concentrations (MICs) of clinically relevant antibiotics were determined by broth microdilution method. Screening for beta-lactam resistance was performed in all isolates following EUCAST recommendation. Finally, relevant changes in penicillin-binding protein 3 (PBP3) were detected by PCR screening. Of the 1481 isolates collected between 2005 and 2019, 12.6%, 0.2%, 17.1%, and 0.2% were resistant to ampicillin, amoxicillin/clavulanate, cefuroxime, and ceftriaxone, respectively. Among them, 74.4% (1102/1481) of isolates were categorized as BLNAS (β-lactamase negative, ampicillin-susceptible), 13.0% (192/1481) as BLNAS with modified PBP3 (mutations in ftsI gene), 2.6% (39/1481) as BLNAR (β-lactamase negative, ampicillin-resistant), and 0.2% had PBP3 modifications typical for high-BLNAR. Production of β-lactamase characterized 9.7% of isolates (8.6% BLPAR-β-lactamase-positive, ampicillin-resistant, and 1.1% BLPACR-β-lactamase-positive, amoxicillin-clavulanate resistant). Three isolates with PBP3 modifications typical for high-BLNAR proved resistant to ceftriaxone (MIC > 0.125mg/L). Resistance to ciprofloxacin, chloramphenicol, tetracycline, and trimethoprim-sulfamethoxazole was observed in 0.1%, 0.5%, 1.6%, and 24.7% of isolates, respectively. This is the first report of Polish H. influenzae isolates resistant to third-generation cephalosporins. Polish H. influenzae isolates demonstrate similar susceptibility trends as in many other countries. The substantial proportion of β-lactam-resistant isolates and the emergence of those resistant to third-generation cephalosporins are of great concern and should be under surveillance.

Population-based surveillance for invasive pneumococcal disease and pneumonia in infants and young children in Goiânia, Brazil

A comprehensive analysis of serotype-specific invasive capacity, clinical presentations, and mortality trends of invasive pneumococcal disease.

From January 1991 through December 1998, a total of 1046 pneumococcal isolates were received from 23 laboratories participating in the statewide surveillance system. Of these, 1037 were recovered from normally sterile sites (blood and cerebrospinal and pleural fluid) and were available for serotyping and susceptibility testing. Ninety-two percent of these isolates were serotypes represented in the 23-valent pneumococcal polysaccharide vaccine. Serotypes in the 7-valent pneumococcal conjugate vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F) were recovered from 72% of Alaska Natives and 84% of non-Native children <5 years old with invasive disease. Statewide, 7.3% and 3.2% of isolates had intermediate and high levels of resistance to penicillin, respectively; 9.2% were resistant to erythromycin (minimal inhibitory concentration, >/=1 microg/mL) and 19% to trimethoprim/sulfamethoxazole (minimal inhibitory concentration, >/=4/76 microg/mL). Twelve percent of invasive isolates were resistant to >/=2 classes of antibiotics; of these, serotype 6B accounted for 33%, and 63% were recovered from children <5 years old.

BackgroundDuring the 2020 SARS-CoV-2 pandemic, physical distancing and mask use guidelines were implemented resulting in a decline in the number of infections caused by influenza, respiratory syncytial virus and otitis media. A surveillance analysis from England and Taiwan showed a decline in invasive pneumococcal disease (IPD) (Clin Infect Dis. 2021;72: e65-75 and J Infect. 2021;82:296-297). We hypothesized that COVID mitigation efforts resulted in a decrease in incidence of pediatric IPD within the U.S. during 2020 compared to previous years.MethodsWe reviewed all cases of IPD among 7 children’s hospitals from the U.S. Pediatric Multicenter Pneumococcal Surveillance Group from 2017-2020. IPD was defined by the isolation of Streptococcus pneumoniae from normally sterile sites (eg. blood, cerebrospinal, pleural, synovial or peritoneal fluid). Pneumococcal pneumonia was defined as an abnormal chest radiograph in the presence of a positive blood, pleural fluid or lung culture. Mastoiditis was identified by positive middle ear, subperiosteal abscess or mastoid bone culture. Serotypes were determined by the capsular swelling method. Hospital admission numbers were obtained for incidence calculations. Statistical analyses were performed using STATA11. A p< 0.05 was considered significant.ResultsA total of 410 IPD cases were identified. The cumulative incidence of IPD (0-22 years of age) decreased from 99.2/100,000 admissions in 2017-2019 to 53.8/100,000 admissions in 2020 (risk ratio 0.54, CI: 0.40-0.72, p< 0.00001). Pneumococcal bacteremia and pneumonia decreased significantly in 2020 (p< 0.05), and although not statistically significant, there were fewer cases of meningitis and mastoiditis when compared to previous years (p=0.08) (Figure 1). Sex, race, age or presence of comorbidities were not significantly different between groups. Most common serotypes in 2020 were 35B, 3 and 15B/C (Figure 2).ConclusionThe observed decline in IPD cases during the first year of the SARS-CoV-2 pandemic is likely associated with mask use and physical distancing limiting transmission of S. pneumoniae via droplets and viral infections frequently preceding IPD. These precautions might be useful in the future to decrease IPD, especially in high-risk patients.DisclosuresSheldon L. Kaplan, MD, Pfizer (Research Grant or Support) Tina Q. Tan, MD, GSK (Individual(s) Involved: Self): Advisor or Review Panel member, Grant/Research Support; ILiAD (Individual(s) Involved: Self): Advisor or Review Panel member; Merck (Individual(s) Involved: Self): Advisor or Review Panel member, Grant/Research Support; Moderna (Individual(s) Involved: Self): Advisor or Review Panel member; Pfizer (Individual(s) Involved: Self): Advisor or Review Panel member Pia S. Pannaraj, MD, MPH, Pfizer (Grant/Research Support)Sanofi-Pasteur (Advisor or Review Panel member)Seqirus (Advisor or Review Panel member) Larry Givner, MD, AstraZeneca (Advisor or Review Panel member) Kristina G. Hulten, PhD, Pfizer (Research Grant or Support)

Detection of beta-lactamase-negative ampicillin resistance in Haemophilus influenzae in Belgium