Conjugate Vaccine Era Research Articles

Pneumococcal Colonization in Healthy Adult Research Participants in the Conjugate Vaccine Era, United Kingdom, 2010-2017.

Pneumococcal colonization is rarely studied in adults, except as part of family surveys. We report the outcomes of colonization screening in healthy adults (all were nonsmokers without major comorbidities or contact with children aged <5 years) who had volunteered to take part in clinical research. Using nasal wash culture, we detected colonization in 6.5% of volunteers (52 of 795). Serotype 3 was the commonest serotype (10 of 52 isolates). The majority of the remaining serotypes (35 of 52 isolates) were nonvaccine serotypes, but we also identified persistent circulation of serotypes 19A and 19F. Resistance to at least 1 of 6 antibiotics tested was found in 8 of 52 isolates.

Acute otitis media in infants younger than two months of age: Epidemiologic and microbiologic characteristics in the era of pneumococcal conjugate vaccines

ObjectivesTo evaluate the epidemiology, microbiology, Streptococcus pneumoniae serotypes distribution and serious bacterial infections (SBIs) occurrence in infants <2 months of age with tympanocentesis-documented acute otitis media (AOM), before and after the introduction of pneumococcal conjugate vaccines (PCVs). MethodsThe medical records of all hospitalized infants with AOM who underwent tympanocentesis during 2005–2014 were reviewed. ResultsOf the 303 infants with AOM who were diagnosed by an ENT specialist, 182 underwent tympanocentesis, 92 during 2005–2009 (prevaccine period) and 90 during 2010–2014 (postvaccine period). Streptococcus pneumoniae and nontypeable Hemophilus influenzae were isolated in 46/92 (50%) and 37/92 (40.2%) patients during 2005–2009 and decreased to 27/90 (30%) and 21/90 (23.3%). Respectively, during 2010–2014 (P = 0.006 and P = 0.001). The proportion of culture-negative patients increased from 18/92 (19.6%) during 2005–2009 to 32/90 (35.6%) during 2010–2014 (P = 0.02). There were only 6 (3.3%) patients <2 weeks of age. The most common S. pneumoniae vaccine serotypes isolated during 2005–2009 were 5, 3, 1, 19F and 14 (15.2%, 13.0%, 10.9%, 6.5%, and 4.3%, respectively) and 3, 5, 1, 14 and 19A (22.2%, 11.1%, 7.4%, 7.4%, and 7.4%, respectively) during 2010–2014. The proportion of culture-positive patients decreased during 2013–2014 compared with 2011–2012 (7/18, 38.9% vs. 40/54, 74.1%, P = 0.007). Serotypes 1 and 5 were not isolated during 2013–2014 and serotype 19A was not isolated during 2011–2014. . SBIs were recorded in 23/182 (12.64%) patients and urinary tract infections represented 19/23 (82.61%) of them (Escherichia coli isolated in 12, 63.2%). ConclusionsThe overall number of AOM cases needing tympanocentesis seen at the PER and the proportion of S. pneumoniae and nontypeable H. influenzae-AOM decreased while the proportion of culture-negative AOM increased following the introduction of PCVs. SBIs associated with AOM were frequent and were represented mostly by urinary tract infections caused by pathogens unrelated to the etiologic agents of AOM.

National Incidence of Pediatric Mastoiditis in the United States, 2000-2012: Creating a Baseline for Public Health Surveillance.

Between 2000 and 2012, the national estimated incidence rate of pediatric mastoiditis, a rare but serious complication of acute otitis media, was highest in 2006 (2.7/100,000 population) and lowest in 2012 (1.8/100,000 population). This measure provides a baseline for public health surveillance in the pneumococcal conjugate vaccine era as stewardship efforts target antibiotic use in acute otitis media.

Invasive Pneumococcal Disease Caused by Non-Vaccine Type Multidrug-Resistant Streptococcus pneumoniae Transmitted by Close Contact in a Healthy Adult.

The incidence of vaccine-type Streptococcus pneumoniae carriage and disease have declined in vaccinated children as well as in unvaccinated children and adults. However, diseases caused by non-vaccine type (NVT) S. pneumoniae are increasing. In this study, we report an invasive pneumococcal disease (IPD) caused by NVT multidrug-resistant (MDR) S. pneumoniae transmitted from a vaccinated infant to an unvaccinated healthy woman, and the clinical characteristics of this serotype. A 29-year-old previously healthy woman visited our hospital with fever and headache. She had been breastfeeding her baby for 8 months. She was diagnosed with brain abscess and sinusitis caused by S. pneumoniae. Although the patient had no previous exposure to antibiotics, antibiotic susceptibility test identified the pathogen as MDR. The patient's family members were examined using nasopharyngeal swabs for bacterial culture. The serotype of S. pneumoniae identified from the blood, abscess, and sputum of the patient was 15B/C. After investing the patient's family members, we found that the serotype from nasopharyngeal specimen of her baby was the same. We described an invasive MDR pneumococcal disease in an immunocompetent young adult in the community. IPD likely spread to the patient by close contact with her baby, who harbored S. pneumoniae of NVT. The spread of NVT S. pneumoniae in the post-vaccine era has increased in the community, and resistance pattern for S. pneumoniae of 15B/C changed compared to the pre-pneumococcal conjugate vaccine era. The spread of MDR pathogens causing IPD among family members should be monitored.

Prevalence of Severe Bacterial Infection in Febrile Children with Sickle CELL Disease in the Era of Pneumococcal Conjugate Vaccine 13

IntroductionThe incidence of invasive pneumococcal infections in patients with sickle cell disease (SCD) decreased after introduction of penicillin prophylaxis and pneumococcal conjugate vaccine (PCV). However, the decrease in pneumococcal infections alone may not necessarily mean an overall decrease in severe bacterial infections (SBI). In a previous publication, we reported a 0.4 % prevalence of pneumococcal bacteremia following introduction of PCV 13. In the current study, we aimed to define the prevalence of SBI and hospitalization in febrile patients in the same cohort in the later years.MethodsWe performed a retrospective study of patients with SCD <18 years old presenting with fever to University of South Alabama Children's and Women's Hospital from January 2014 to June 2017. SBI was defined as: bacteremia, pneumonia, pyelonephritis, meningitis, osteomyelitis and abscess (superficial and deep). Univariate analysis and multivariate logistic regression were used to determine factors associated with patient disposition as well as presence of SBI.ResultsThere were 258 febrile events in 120 patients resulting in 187 (72%) admissions (figure 1). SBI was seen in 12% of admissions with uncomplicated community acquired pneumonia being the most common. The prevalence of bacteremia was 1.6% with single cases of pneumococcus, E. coli, and H. influenzae bacteremia. Younger age, high fever, and splenectomy were associated with hospitalization (p<0.05). However, only C reactive protein was associated with SBI (p<0.02). Viral infection was diagnosed in 80% of outpatients but 87% were given antibiotics. Among inpatients, all received parenteral antibiotics, and 67% were assessed to have viral illness, although only 23% had a virus identified. Pneumococcal vaccination status was satisfactory in 77% of our sample while compliance rate with penicillin prophylaxis was >85% in both inpatient and outpatient groups.ConclusionAlthough majority of febrile events were due to viral infections, 3 of four febrile episodes in our cohort resulted in hospitalization. A small proportion of patients had SBI and a much smaller proportion had bacteremia. These findings support early virus identification which can have implications on patient discharge disposition and antibiotic use. Further studies looking at risk stratification of febrile patients with SCD are needed to encourage outpatient management without compromising safety. [Display omitted] DisclosuresImran:Novo Nordask: Speakers Bureau.

No Demonstrable Benefit of Penicillin in a Vaccinated Population of Children with Sickle Cell Disorder

UK and many National guidelines advise on the use of prophylactic antibiotics, immunisation and patient education to minimise the risk of severe infections by encapsulated organisms in patients with Sickle Cell Disorder. The UK vaccination schedule for sickle cell anaemia patients includes Pneumococcal, Meningococcal and Haemophilus influenzae type B (Hib) immunisation. Prophylactic Penicillin V is recommended as additional protection against Streptococcus pneumoniae (S.pneumoniae).In light of the findings in the papers by Oligbu et al, 2017, and Martin et al 2018, we aimed to retrospectively compare compliance with prophylactic Penicillin V against infection rates by S.pneumoniae,Neisseria meningitidis (N.meningitidis) and Hib . We hypothesised that the incidence of infections with IPD and other encapsulated organisms would be greater in patients who were not adherent with Penicillin V. Patients were considered compliant with prophylactic Penicillin V if 75% or more of their urine samples gave positive results.The study population consisted of 52 Sickle Cell patients, ranging from age 3 to 20years.Three patients were excluded as no urine samples had been collected from them in the 5 year period. Of the remaining 49 patients only 9 patients (18%) were had good adherence with Penicillin V over a 5 year period.100% of patients received prevenar vaccination (PCV-7 or PCV 13).73% received additional pneumovax.We retrospectively reviewed microbiology culture reports over a five year period. All microbiology reports were reviewed from the period, with the virulent encapsulated organisms of S.pneumoniae,N.meningitidis and Hib recorded, alongside any other bacterial infections.No patients had microbiological evidence of infection by virulent encapsulated bacteria. Six patients had cultures positive for other organisms: two Staphylococcus aureus positive sputum cultures, one Salmonella positive stool culture, two urine cultures positive for Escherichia coli, and one skin wound swab positive for Streptococcus pyogenes.Of the 6 organisms identified, 3 occurred in patients compliant with Penicillin V, and 3 occurred in patients who were non-compliant. Patients compliant with Penicillin V formed a small cohort (n=9), resulting in an apparently high incidence of infection (33%). In the non-compliant cohort (n=40), 8% had shown infection. Analysis by Fisher's Exact Test confirmed no significant difference in the incidence of infection between the two groups (p= 0.06).In a sickle cell disorder population where 82% of the patients were not 100% compliant with prophylactic Penicillin V, no significant encapsulated bacteria (S.pneumoniae,N.meningitidis or Hib) were cultured in a 5 year period in our cohort. Non-compliance with prophylactic Penicillin V was not associated with an increased incidence of infections by encapsulated organisms.The UK study (Oligbu et al) on IPD was performed in the PCV13 era and states a 49x increased risk of developing IPD and a 5x increase in mortality in children with sickle cell compared to their peers. However, most IPD cases were due to non-vaccine serotypes. A similar study from the US (Martin et al) found deaths only in the PCV7 cohort, it does not state if the patients were vaccinated with pneumovax 23.In conclusion 82% of children did not adhere to penicillin. We have not demonstrated any benefit in adhering to prophylactic penicillin. Adherence is poor and alternative approaches of standby antibiotics should be considered. We suggest focusing on vaccination as a preventative strategy is of more benefit. Martin OO, Moquist KL, Hennessy,JM, Nelson SC. Invasive pneumococcal disease in children with sickle cell disease in the pneumococcal conjugate vaccine era. Pediatr Blood Cancer. 2018;65:e26713. https://doi.org/10.1002/pbc.26713Oligbu G, Collins S , Streetly A, Dick, M, Ladhany, S. Risk of invasive pneumococcal disease in children with sickle cell disease in England: National observational cohort study, 2010 - 2015. Arch Dis Child 2017;102(Suppl1):A4-A4 DisclosuresNo relevant conflicts of interest to declare.

Invasive Pneumococcal Disease in UK Children

Invasive pneumococcal disease (IPD) has declined significantly since the introduction of pneumococcal conjugate vaccines (PCVs). It is not known whether certain infant populations remain at higher risk of IPD in countries with established 13-valent PCV (PCV13) programs. We aimed to describe the epidemiology, clinical characteristics, serotype distribution, and outcomes of IPD in infants, and to estimate the relative risk of PCV13-type, non-PCV13-type, and overall IPD in premature infants compared to term infants during a 4-year period after the PCV13 program was established. This was a prospective, enhanced national surveillance of laboratory-confirmed IPD in England in infants aged <1 year diagnosed during 2013-2016. There were 517 cases of IPD (incidence: 19/100000 infants). Incidence was significantly higher in premature infants compared with those born at term (49/100000 vs 17/100000; incidence rate ratio [IRR], 2.87; P < .001), with infants born before 28 weeks' gestation having the highest incidence (150/100000; IRR, 8.8; P < .001). Of the 454 IPD cases with serotyped isolates, most were caused by non-PCV13 serotypes (369 cases, 71.4%), with 85 cases (16.4%) due to PCV13 serotypes. There were 31 deaths (case fatality rate [CFR], 6.2% [95% confidence interval, 4.3%-8.6%]). Premature infants did not have a higher CFR than term infants (P = .62). IPD incidence in infants remains lower than rates reported prior to PCV7 introduction in England. The risk of IPD remains significantly higher in premature infants compared to infants born at term, for both PCV13 and non-PCV13 serotypes. Any changes to the infant PCV13 immunization schedule may disproportionally affect premature infants.

Utility of the Performance of Lumbar Puncture for Febrile Children With Status Epilepticus in the Bacterial Conjugate Vaccine Era.

The necessity of lumbar puncture for the differentiation of central nervous system infection in children with febrile status epilepticus (FSE) remains controversial. The aim of the present study is to investigate the diagnostic necessity of lumbar puncture for children with FSE after the introduction of bacterial conjugate vaccines into the infant immunization program. Our retrospective cohort study was performed in children 6 to 60 months of age who were admitted to the pediatric ward at Kitakyushu General Hospital from January 1, 2011, to December 31, 2015, for seizures with fever. Of these patients, we compared the clinical characteristics between the patients initially diagnosed as having FSE and complex febrile seizures excluding FSE (non-FSE). Of the eligible 333 children, 98 and 235 children were classified into FSE and non-FSE groups, respectively. The proportion of the children who underwent lumbar puncture in FSE group was significantly higher than that in non-FSE group (P < 0.0001). On the other hand, no significant difference in the proportion of the patients with abnormal cerebrospinal fluid findings was seen between the 2 groups. There was no patient with bacterial meningitis. The proportion of patients with encephalitis/encephalopathy in FSE group (n = 7, 7.1%) was significantly higher than that in non-FSE group (n = 0, P = 0.0003). However, only 1 of 6 patients with encephalitis/encephalopathy who underwent lumber puncture showed pleocytosis in cerebrospinal fluid. Routine lumbar puncture for the differentiation of severe central nervous system infection cannot be recommended in children with FSE.

Characteristics of Streptococcus pneumoniae serotype 19A isolates from children in the pre and post Conjugate Vaccine Era. Single center experience 1986–2015

BackgroundThe present study assessed the prevalence and characteristics of S. pneumoniae serotype 19A isolates from children with pneumococcal disease (PD), before and since introduction of pneumococcal conjugate vaccines (PCVs) in Greece. MethodsS. pneumoniae isolates collected at one large pediatric hospital between 1986 and 2015 were serotyped by the Quellung reaction and MICs determined by Etest. Alterations of pbp genes and the presence of mefA, mefE, ermB genes were detected by polymerase chain reaction. Genotypes were assessed by multilocus sequence typing (MLST). ResultsAmong 1875 isolates, 210 (11.2%) belonged to serotype 19A. The prevalence of PD caused by serotype 19A increased from 4.6% in the pre-PCV7 years (1986–2005) to 19.6% in the post-PCV7 years (2006–2010), peaking at 27% in 2009 (p < 0.001, 95% CI; 2.0, 18.2) with a significant upward trend (p = 0.04, 95% CI; 1.02, 12.66). Following the introduction of PCV13 in 2010, the rate decreased from 22% in 2011 to 11.4% in 2015 (p = 0.08, 95% CI; 0.92, 5.1) with a downward trend of borderline significance (p = 0.05, 95% CI; −6.8, 0.04). The multidrug resistant (MDR) serotype 19A isolates increased from 10.6% in 1986–2005 to 21.2% in 2006–2010 and to 71.8% in 2011–2015 (P < 0.001). Alterations in pbp genes were detected in all penicillin non-susceptible isolates. Of 110 erythromycin resistant isolates, 21 contained the mefE gene, 36 the ermB and 53 both the mefE and ermB genes. MLST analysis of 142 isolates revealed four dominant clonal complexes (CC); CC320, CC172, CC276 and CC199. The majority of CC320 and CC276 isolates displayed MDR phenotypes. ConclusionPD caused by serotype 19A increased significantly after the introduction of PCV7 followed by a decline after PCV13 use. The vast majority of persisting 19A isolates was MDR. Surveillance studies are necessary to monitor the changes in the pneumococcal population.

Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000-15.

SummaryBackgroundPneumococcal conjugate vaccine (PCV) and Haemophilus influenzae type b (Hib) vaccine are now used in most countries. To monitor global and regional progress towards improving child health and to inform national policies for disease prevention and treatment, we prepared global, regional, and national disease burden estimates for these pathogens in children from 2000 to 2015.MethodsUsing WHO and Maternal and Child Epidemiology Estimation collaboration country-specific estimates of pneumonia and meningitis mortality and pneumonia morbidity from 2000 to 2015, we applied pneumococcal and Hib cause-specific proportions to estimate pathogen-specific deaths and cases. Summary estimates of the proportion of pneumonia deaths and cases attributable to these pathogens were derived from four Hib vaccine and six PCV efficacy and effectiveness study values. The proportion of meningitis deaths due to each pathogen was derived from bacterial meningitis aetiology and adjusted pathogen-specific meningitis case–fatality data. Pneumococcal and Hib meningitis cases were inferred from modelled pathogen-specific meningitis deaths and literature-derived case–fatality estimates. Cases of pneumococcal and Hib syndromes other than pneumonia and meningitis were estimated using the ratio of pathogen-specific non-pneumonia, non-meningitis cases to pathogen-specific meningitis cases from the literature. We accounted for annual HIV infection prevalence, access to care, and vaccine use.FindingsWe estimated that there were 294 000 pneumococcal deaths (uncertainty range [UR] 192 000–366 000) and 29 500 Hib deaths (18 400–40 700) in HIV-uninfected children aged 1–59 months in 2015. An additional 23 300 deaths (15 300–28 700) associated with pneumococcus and fewer than 1000 deaths associated Hib were estimated to have occurred in children infected with HIV. We estimate that pneumococcal deaths declined by 51% (7–74) and Hib deaths by 90% (78–96) from 2000 to 2015. Most children who died of pneumococcus (81%) and Hib (76%) presented with pneumonia. Less conservative assumptions result in pneumococcccal death estimates that could be as high as 515 000 deaths (302 000–609 000) in 2015. Approximately 50% of all pneumococcal deaths in 2015 occurred in four countries in Africa and Asia: India (68 700 deaths, UR 44 600–86 100), Nigeria (49 000 deaths, 32 400–59 000), the Democratic Republic of the Congo (14 500 deaths, 9300–18 700), and Pakistan (14 400 deaths, 9700–17 000]). India (15 600 deaths, 9800–21 500), Nigeria (3600 deaths, 2200–5100), China (3400 deaths, 2300–4600), and South Sudan (1000 deaths, 600–1400) had the greatest number of Hib deaths in 2015. We estimated 3·7 million episodes (UR 2·7 million–4·3 million) of severe pneumococcus and 340 000 episodes (196 000–669 000) of severe Hib globally in children in 2015.InterpretationThe widespread use of Hib vaccine and the recent introduction of PCV in countries with high child mortality is associated with reductions in Hib and pneumococcal cases and deaths. Uncertainties in the burden of pneumococcal disease are largely driven by the fraction of pneumonia deaths attributable to pneumococcus. Progress towards further reducing the global burden of Hib and pneumococcal disease burden will depend on the efforts of a few large countries in Africa and Asia.FundingBill & Melinda Gates Foundation.

Non-typeable Streptococcus pneumoniae infection in a medical center in Taiwan after wide use of pneumococcal conjugate vaccine.

Streptococcus pneumoniae is one of the most common pathogens to cause mucosal and invasive infection in humans. Most of the infection could be prevented through immunization by vaccines containing capsular polysaccharides but some infection may be caused by unencapsulated strains. Clinical isolates of S.pneumoniae from January 2012 to December 2015at Chang Gung Memorial Hospital, Taiwan. Serotyping by PCR method was performed. Clinical and laboratory information of patients infected by non-typeable pneumococci (NTP) were collected and analyzed. During the study period, 39 NTP isolates were identified. Most (21 of 39, 53.9%) were collected from purulent upper respiratory tract secretion. Others were from corneal abscess, sputum, and one from blood of a newborn. We recorded a 3.6-fold increase in the rate of isolation from 1.4% in 2012 to 5.0% in 2015 (p=0.063). Co-infection was found in 24 cases; the major co-infecting pathogens included non-typeable Hemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Most (39 of 40, 97.5%) of the isolates were susceptible to both penicillin and ceftriaxone. The dominant sequence type ST1106 and an emerging sequence type ST7502 were recognized. A gradual increase of NTP infection was found in northern Taiwan in the pneumococcal conjugate vaccine era. Non-typeable pneumococci can cause respiratory and ophthalmological mucosal infection. Invasive infection can occur in newborns or young infants. Most of the isolates remained susceptible to penicillin and ceftriaxone.

Short-course antimicrobial therapy for paediatric respiratory infections (SAFER): study protocol for a randomized controlled trial

BackgroundCommunity-acquired pneumonia (CAP) is commonly diagnosed in children. The Infectious Disease Society of America guidelines recommend 10 days of high-dose amoxicillin for the treatment of non-severe CAP but 5-day “short course” therapy may be just as effective. Randomized trials in adults have already demonstrated non-inferiority of 5-day short-course treatment for adults hospitalized with severe CAP and for adults with mild CAP treated as outpatients. Minimizing exposure to antimicrobials is desirable to avoid harms including diarrhoea, rashes, severe allergic reactions, increased circulating antimicrobial resistance, and microbiome disruption.MethodsThe objective of this multicentre, randomized, non-inferiority, controlled trial is to investigate whether 5 days of high-dose amoxicillin is associated with lower rates of clinical cure 14–21 days later as compared to 10 days of high-dose amoxicillin, the reference standard. Recruitment and enrolment will occur in the emergency departments of McMaster Children’s Hospital and the Children’s Hospital of Eastern Ontario. All children in the study will receive 5 days of amoxicillin after which point they will receive either 5 days of a different formulation of amoxicillin or a placebo. Assuming a clinical failure rate of 5% in the reference arm, a non-inferiority margin of 7.5%, one-sided alpha set at 0.025 and power of 0.80, 270 participants will be required. Participants from a previous feasibility study (n = 60) will be rolled over into the current study. We will be performing multiplex respiratory virus molecular testing, quantification of nasopharyngeal pneumococcal genomic loads, salivary inflammatory marker testing, and faecal microbiome profiling on participants.DiscussionThis is a pragmatic study seeking to provide high-quality evidence for front-line physicians evaluating children presenting with mild CAP in North American emergency departments in the post-13-valent pneumococcal, conjugate vaccine era. High-quality evidence supporting the non-inferiority of short-course therapy for non-severe paediatric CAP should be generated prior to making changes to established guidelines. Trial registrationClinicalTrials.gov, NCT02380352. Registered on 2 March 2015.

Disease Burden and Etiologic Distribution of Community-Acquired Pneumonia in Adults: Evolving Epidemiology in the Era of Pneumococcal Conjugate Vaccines.

Pneumonia is the leading cause of morbidity and mortality, particularly in old adults. The incidence and etiologic distribution of community-acquired pneumonia is variable both geographically and temporally, and epidemiology might evolve with the change of population characteristics and vaccine uptake rates. With the increasing prevalence of chronic medical conditions, a wide spectrum of healthcare-associated pneumonia could also affect the epidemiology of community-acquired pneumonia. Here, we provide an overview of the epidemiological changes associated with community-acquired pneumonia over the decades since pneumococcal conjugate vaccine introduction.

Osteoarticular Infections Caused by Streptococcus pneumoniae in Children in the Post-Pneumococcal Conjugate Vaccine Era.

Pneumococcal osteoarticular infections (OAIs) are an uncommon manifestation of invasive pneumococcal disease (IPD). We describe the demographic characteristics, hospitalization rate, serotype distribution and antibiotic susceptibility of children with pneumococcal OAI over a 16-year period. We identified patients ≤18 years old with pneumococcal OAI at 8 children's hospitals in the United States (2000-2015). Pneumococcal isolates were collected prospectively. Serotyping and antibiotic susceptibility were performed in a central laboratory. We identified 97 (3.3%) patients with pneumococcal OAI out of 2943 patients with IPD. Over 60% of the children were <2 years old. Septic arthritis (56.7%, 55/97) was the most common pneumococcal OAI, followed by osteomyelitis (25.8%, 25/97) and septic arthritis with concomitant osteomyelitis (17.5%, 17/97). Hospitalization for pneumococcal OAI overall decreased from 6.8 [95% confidence interval (CI): 5.2-8.6] to 4.4 (95% CI: 3.0-6.3) per 100,000 admissions from 2000-2009 to 2010-2015 (-35%, P = 0.05). Hospitalization for pneumococcal OAI caused by PCV13 serotypes decreased from 4.6 (95% CI: 3.4-6.2) to 0.9 (95% CI: 0.3-1.9) per 100,000 admissions from 2000-2009 to 2010-2015 (-87%, P < 0.0001). Overall, 12% of isolates had a penicillin minimal inhibitory concentration> 2 µg/mL, 3% a ceftriaxone minimal inhibitory concentration> 1 µg/mL and 15% were clindamycin resistant; these proportions remained unchanged after the introduction of PCV13. Serotypes 19A and 35B were responsible for penicillin and ceftriaxone nonsusceptible isolates in 2010-2015. Pneumococcal OAI represents 3% of all IPD, affecting mainly healthy infants and young children. Hospitalization for pneumococcal OAI caused by PCV13 serotypes dramatically decreased (-87%) after the introduction of PCV13.

Change in Pneumococcus Serotypes but not Mortality or Morbidity in Pre- and Post-13-Valent Polysaccharide Conjugate Vaccine Era: Epidemiology in a Pediatric Intensive Care Unit over 10 Years.

Pneumococcus is a common commensal and an important pathogen among children for which immunization is available. Some serotypes occasionally cause severe pneumococcal disease with high mortality and morbidity. We reviewed all pneumococcal serotypes and mortality/morbidity in a pediatric intensive care unit (PICU) following universal pneumococcal conjugate vaccine (PCV) immunization. A 13-valent PCV was introduced in the universal immunization program in late 2011 in Hong Kong. We retrospectively reviewed all pneumococcal serotypes in the pre-(2007-11) and post-(2012-16) 13-valent PCV era. There were 29 (1.9%) PICU patients with pneumococcal isolation, of which 6 died (20% motality). Serogroups 6 and 19 predominated before and Serogroup 3 after 2012. In the post-13-valent PCV era, the prevalence of pneumococcus isolation in PICU was increased from 1 to 2% (p = 0.04); Serogroup 3 was the major serotype of morbidity, despite supposedly under vaccine coverage. The majority of pneumococcus were penicillin-sensitive (94%) in the post 13-valent PCV era. All pneumococcus specimens were sensitive to cefotaxime and vancomycin. Binary logistic regression showed that there were reductions in Serogroup 6 (odds ratio [OR], 0.050; 95% confidence interval [CI], 0.004-0.574; p = 0.016) and Serogroup 19 (odds ratio [OR], 0.105; 95% confidence interval [CI], 0.014-0.786; p = 0.028) but not mortality or morbidity for patients admitted after 2012. SPD is associated with significant morbidity and mortality, despite treatment with systemic antibiotics and ICU support. The expanded coverage of 13-valent PCV results in the reduction of Serotypes 6 and 19 but not mortality/morbidity associated with SPD in the setting of a PICU.

Playing "Whack-a-Mole" With Pneumococcal Serotype Eradication.

* Abbreviations: AOM — : acute otitis media IPD — : invasive pneumococcal disease PCV — : pneumococcal conjugate vaccine PCV7 — : 7-valent pneumococcal conjugate vaccine PCV13 — : 13-valent pneumococcal conjugate vaccine NP — : nasopharyngeal SPN — : Streptococcus pneumoniae In this issue of Pediatrics , Lee et al1 report surveillance data from Massachusetts communities regarding Streptococcus pneumoniae (SPN) colonization during the pneumococcal conjugate vaccine (PCV) era. Nasopharyngeal (NP) colonization is thought to precede SPN disease, so it is a reasonable measure of circulating (and potentially disease-producing) pneumococcal strains. Three aspects are notable: (1) shifting serotypes of known invasive pneumococcal disease (IPD) producers; (2) risk factors for colonization; and (3) evolving antibiotic resistance. Excluding HIV-associated pneumococcal deaths, global estimates attribute ∼11% of all deaths in children 1 to 59 months of age to SPN disease.2 SPN remains a concern for US practitioners, causing both IPD (eg, meningitis, pneumonia, and bacteremia) and noninvasive disease (eg, acute otitis media [AOM] and sinusitis). Practitioners likely see at least 1 child per week for whom SPN bacteremia, pneumonia, or meningitis is a concern. A preventive vaccine targeting the most common IPD strains seemed a reasonable strategy to reduce disease burden and ease providers’ fears of missing an impending severe IPD case. Introduced in 2000, 7-valent PCV (PCV7) markedly decreased IPD among PCV7 recipients,3–6 and also among non-PCV7 … Address correspondence to Douglas S. Swanson, MD, Infectious Diseases, Children’s Mercy Kansas City, 2401 Gillham Rd, Kanas City, MO 64108. E-mail: dswasnon{at}cmh.edu

Invasive Pneumococcal Disease in Children With Sickle Cell Anemia

Research Article| November 01 2017 Invasive Pneumococcal Disease in Children With Sickle Cell Anemia AAP Grand Rounds (2017) 38 (5): 57. https://doi.org/10.1542/gr.38-5-57 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Invasive Pneumococcal Disease in Children With Sickle Cell Anemia. AAP Grand Rounds November 2017; 38 (5): 57. https://doi.org/10.1542/gr.38-5-57 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: invasive pneumococcal disease, sickle cell anemia Source: Martin OO, Moquist KL, Hennessy JM, et al. Invasive pneumococcal disease in children with sickle cell disease in the pneumococcal conjugate vaccine era. Pediatr Blood Cancer. 2017 4 July [published online ahead of print]; doi: https://doi.org/10.1002/pbc.26713Google Scholar Investigators from Michigan State University, Flint, MI, and Children’s Hospitals and Clinics of Minnesota (CHCM), Minneapolis, MN, conducted a retrospective study to assess trends in invasive pneumococcal disease (IPD) among children with sickle cell disease (SCD) in the era of universal pneumococcal immunization for young children. For the study, they reviewed medical records and microbiological databases at CHCM to identify cases of IPD in children with SCD between 2000 and 2014. IPD was defined as the presence of pneumococcus in a blood or cerebrospinal fluid culture. Data collected on study patients included age, pneumococcal immunization status, pneumococcus serotype, and penicillin susceptibility. On the basis of the number of cases identified and the population of patients with SCD followed up at CHCM, the investigators estimated the incidence of IPD per 100,000 person-years among children with SCD. In addition to describing clinical characteristics of cases of IPD over the entire study period, observations were divided into 2 periods on the basis of the type of pneumococcal conjugate vaccine available. Thus, in period 1, 2000–2010, the pneumococcal conjugate vaccine (PCV) against 7 serotypes (PCV7) was available, and in period 2, 2010–2014, the 13-valent PCV (PCV13) was used. During the overall study period, 11 cases of IPD in patients with SCD were identified, including 7 in period 1 and 4 in period 2. The mean age of study patients was 5 years, with a range of 6 months to 11 years. Two children with IPD died; information on pneumococcus serotype was available for the remaining 9 patients. PCV data were available for 8 of these 9 children, and data for all 8 were classified as being up to date. During period 1, all cases of IPD were caused by serotypes of pneumococcus not included in PCV7; during period 2, 1 patient (an 8-year-old boy) had IPD caused by serotype 7F (included in PCV13 but not PCV7). All isolates tested (n = 9) were sensitive to penicillin. The overall incidence of IPD in children with SCD in this study was estimated at 417 per 100,000 patient-years, with an incidence of 390 per 100,000 patient-years in period 1 and 450 per 100,000 patient-years in period 2. The authors conclude that even in the era of universal pneumococcal immunization, children with SCD remain at risk for IPD. Dr Winer has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. When considering a prophylactic intervention, one must take into account both the burden of the potential disease and the effect of the proposed intervention. In this brief report, the authors argue for both penicillin and PCV prophylaxis in patients with SCD <5 years of age, which is the... You do not currently have access to this content.

Macrolides in Children With Community-Acquired Pneumonia: Panacea or Placebo?

Pneumonia, most often caused by a respiratory virus, is common in childhood. Mycoplasma pneumoniae also is detected frequently, particularly in older children in the era of pneumococcal conjugate vaccination. Despite recommendations for β-lactam antibiotics, macrolide antibiotics, including erythromycin, clarithromycin, and azithromycin, are prescribed frequently to children with acute lower respiratory infection. However, the significance of detecting "atypical" pathogens, including M pneumoniae, in children remains contentious. Considering the potential for antibacterial and anti-inflammatory activities of macrolides, our understanding of the role of these drugs in acute and chronic infections and in inflammatory conditions is changing. Some observational data have revealed improved outcomes in adults and children with pneumonia who are prescribed macrolides, although its widespread use has led to increases in macrolide resistance in Streptococcus pneumoniae and M pneumoniae. Clinical trials to define the role of macrolides in pediatric acute respiratory infection must be prioritized.

Epidemiology of Acute Otitis Media in the Postpneumococcal Conjugate Vaccine Era.

To study the epidemiology of acute otitis media (AOM), especially the otitis-prone condition, during the pneumococcal conjugate vaccines 7 and 13 era. Six hundred and fifteen children were prospectively managed from 6 to 36 months of life during a 10-year time frame (June 2006-June 2016). All clinical diagnoses of AOM were confirmed by tympanocentesis and bacterial culture of middle ear fluid. By 1 year of age, 23% of the children experienced ≥1 episode of AOM; by 3 years of age, 60% had ≥1 episodes of AOM, and 24% had ≥3 episodes. The peak incidence occurred at 6 to 12 months of life. Multivariable analysis of demographic and environmental data revealed a significantly increased risk of AOM associated with male sex, non-Hispanic white race, family history of recurrent AOM, day care attendance, and early occurrence of AOM. Risk factors for stringently defined (tympanocentesis-confirmed) otitis proneness, in which children suffered at least 3 episodes of AOM in a 6-month period or at least 4 within a year, were male sex, day care attendance, and family history of AOM, whereas breastfeeding in the first 6 months of life was protective. Stringently defined otitis prone children were also likely to experience their first AOM episode at a younger age. The proportion of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis causing AOM had dynamic changes during the past decade. We conclude that the epidemiology but not the risk factors for AOM have undergone substantial changes since the introduction of pneumococcal conjugate vaccines.

Pneumococcal Conjugate Vaccine Prevents Pneumonia Hospitalizations

Research Article| September 01 2017 Pneumococcal Conjugate Vaccine Prevents Pneumonia Hospitalizations AAP Grand Rounds (2017) 38 (3): 29. https://doi.org/10.1542/gr.38-3-29 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Pneumococcal Conjugate Vaccine Prevents Pneumonia Hospitalizations. AAP Grand Rounds September 2017; 38 (3): 29. https://doi.org/10.1542/gr.38-3-29 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: 13-valent pneumococcal vaccine, pneumonia, vaccines, conjugate, serotype, invasive pneumococcal disease Source: Olarte L, Barson WJ, Barson RM, et al. Pneumococcal pneumonia requiring hospitalization in US children in the 13-valent pneumococcal conjugate vaccine era. Clin Infect Dis. 2017; 64(12): 1699– 1704; doi: https://doi.org/10.1093/cid/cix115Google Scholar Investigators at multiple institutions conducted a cross-sectional study to assess the prevalence and characteristics of pneumococcal pneumonia (PP) before and after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in 2010. Children were eligible if they were ≤18 years old and had PP managed as an inpatient at 1 of 8 participating US children’s hospitals from 2006 to 2014. PP was defined as the isolation of Streptococcus pneumoniae from blood, pleural fluid, lung abscess, or lung tissue, with clinical presentation and radiographic changes consistent with pneumonia. PP was categorized as complicated if there was pulmonary consolidation plus a large pleural effusion (>10-mm rim or ≥25% of the hemithorax opacified), loculated pleural fluid, parapneumonic empyema, necrotizing pneumonia, or lung abscess. Demographic, clinical, and S pneumoniae serotype data were obtained from the medical chart. Investigators compared annual hospitalization rates for all PP, complicated PP, and serotype-specific PP before (2006–2009) and after (2011–2014) PCV13 introduction. There were 377 patients with PP included in the analysis. The hospitalization rate for all PP decreased from 53.6 per 100,000 admissions before PCV13 to 23.3 per 100,000 admissions after PCV13 (P < .0001). Hospitalization rates for complicated PP also decreased significantly. Comorbid conditions were more common among children with uncomplicated pneumonia than complicated pneumonia (52.2% vs 22.5%, respectively; P< .001). The need for intensive care and invasive procedures did not change after the introduction of PCV13. A total of 364 of 377 isolates (96.6%) were available for serotyping and antibiotic susceptibility testing. Although there was a significant decrease in hospitalization rates for PP caused by PCV13 serotypes, they still accounted for 70% of PP cases in the post-PCV13 era (2011–2014). There was no increase in the hospitalization rate of PP caused by non-PCV13 serotypes (4.3 per 100,000 admissions before PCV13 vs 6.7 per 100,000 admissions after PCV13; P = .1). The proportion of isolates susceptible to penicillin increased from 90.8% in 2006–2009 to 97% in 2011–2014 (P = .05). A lower proportion of isolates associated with complicated (91.3%) versus uncomplicated (98.2%) PP were susceptible to penicillin (P = .015). The investigators conclude that hospitalization rates for PP have decreased since the introduction of PCV-13. Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. The results of the current study agree with those of previous studies, 1,2 which demonstrated a significant decline in the incidence of invasive pneumococcal disease (IPD) among children after the introduction of PCV13. These observations contrast to those for the incidence of pneumococcal meningitis, which, as of 2013, had remained unchanged among these same 8 US children’s hospitals. (See AAP Grand Rounds 2015;34[6]:65.3 )... You do not currently have access to this content.