Pneumococcal Pneumonia Requiring Hospitalization in US Children in the 13-Valent Pneumococcal Conjugate Vaccine Era.

BACKGROUND.: The impact of PCV13 on a number of clinical aspects of pneumococcal pneumonia (PP) in children has not been reported. We compared the serotype distribution, antibiotic susceptibility, and outcomes of children with PP 4 years before and 4 years after the introduction of PCV13. METHODS.: We identified patients ≤18 years with PP at 8 children's hospitals in the United States (2006-2014). Pneumococcal isolates were collected prospectively. Serotyping and antibiotic susceptibility were performed in a central laboratory. Clinical and laboratory data were collected retrospectively. Annual pneumococcal pneumonia hospitalization rates per 100 000 admissions with 95% confidence intervals were calculated. Dichotomous variables were analyzed by χ2 test and continuous variables with Mann-Whitney U test. RESULTS.: A total of 377 patients with PP requiring hospitalization were identified. Hospitalization rates of PP decreased from 53.6 to 23.3 per 100000 admissions post PCV13 (P < .0001). Complicated PP rates also decreased (P < .0001). Need for intensive care, mechanical ventilation, and invasive procedure remained unchanged after the introduction of PCV13. Comorbidities were more common among children with uncomplicated than complicated pneumonia (52.2% vs. 22.5%, P < .001). Overall, PCV13 serotypes 19A, 3, 7F, and 1 caused 80% of PP. Hospitalization rates of PCV13 serotype pneumonia decreased from 47.2 to 15.7 per 100000 admissions post PCV13. In 2014, the most common serotypes were 3, 19A and 35B. CONCLUSIONS.: PP requiring hospitalization significantly decreased in children after PCV13 introduction. Complicated PP rates decreased steadily in 2011-2014. PCV13 serotypes 19A and 3 were still responsible for half of the cases of PP in 2011-2014.

Emergence of Multidrug-Resistant Pneumococcal Serotype 35B among Children in the United States.

Streptococcus pneumoniae serotype 35B is a nonvaccine serotype associated with high rates of penicillin nonsusceptibility. An increase in the proportion of multidrug-resistant (MDR) 35B isolates has recently been reported. The genetic events contributing to the emergence of MDR serotype 35B are unknown. The sequence type (ST) composition of 78 serotype 35B isolates obtained from pediatric patients with invasive pneumococcal disease from 1994 to 2014 and 48 isolates from pediatric patients with otitis media (noninvasive) from 2011 to 2014 was characterized by multilocus sequence typing (MLST). The most common STs were ST558 (69.2%), ST156 (10.3%), and ST452 (3.8%). Two major clonal complexes (CC), CC558 and CC156, were identified by eBURST analysis. Overall, 91% (71/78) of isolates were penicillin nonsusceptible and 16.7% (13/78) were MDR. Among all invasive serotype 35B isolates, MDR isolates increased significantly, from 2.9% (1/35) to 27.9% (12/43) (P = 0.004), after the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced. All CC156 isolates were identified after the introduction of PCV13 (0/35 [0%] before versus 9/43 [20.9%] after; P = 0.003) and were MDR. All CC156 isolates had similar antimicrobial susceptibility patterns; in contrast, high variability in antimicrobial susceptibility was observed among CC558 isolates. The distributions of CC558 and CC156 among invasive and noninvasive isolates were not different. The increased prevalence of MDR serotype 35B after the introduction of PCV13 was directly associated with the emergence of ST156. Genotyping suggests that capsular switching has occurred between MDR vaccine serotypes belonging to ST156 (e.g., 9V, 14, and 19A) and serotype 35B.

Invasive pneumococcal infections in children following transplantation in the pneumococcal conjugate vaccine era.

BACKGROUND: Pediatric recipients of hematopoietic stem cell and solid organ transplants are at increased risk of invasive pneumococcal infections (IPI). Data on IPI in this population are scarce. To our knowledge, this is the first study describing the epidemiology of IPI among pediatric transplant recipients in the pneumococcal conjugate vaccine (PCV) era. METHODS: We identified transplant recipients with IPI at 8 children's hospitals in the U.S. from our surveillance database (2000-2014). Pneumococcal isolates were collected prospectively. Serotyping and antibiotic susceptibility were performed in a central laboratory. Categorical variables were analyzed by Fisher's exact test and continuous variables with nonparametric tests. Indirect cohort study design was used to calculate vaccine effectiveness. RESULTS: We identified 65 episodes of IPI in transplant recipients. Recurrent IPI was observed in 10% of transplant recipients. The IPI crude incidence rate in solid organ transplant recipients was higher than in the general population. Most IPI episodes occurred >6 months after transplantation. Bacteremia and pneumonia were the most common presentations. Meningitis was unusual. No case fatalities were observed. Serotype 19A was the most common serotype (n=10), followed by 6C (n=7). In 2010-2014, 37% of IPI was caused by PCV13 serotypes. Four cases of vaccine breakthrough were identified. Most isolates were susceptible to penicillin and ceftriaxone. Pneumococcal conjugate and polysaccharide immunization rates were low. CONCLUSION: Pediatric transplant recipients remain at increased risk of IPI in the vaccine era. Most cases presented as a late post-transplant infection. The interval between transplantation and IPI may allow adequate time for pneumococcal immunization.

Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Meningitis in US Children.

BACKGROUND: The impact of 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis (PM) in US children is unknown. We compared the serotype distribution, antibiotic susceptibility, hospital course, and outcomes of children with PM 3 years before and 3 years after the introduction of PCV13. METHODS: We identified patients ≤ 18 years of age with PM at 8 children's hospitals in the United States. Pneumococcal isolates were collected prospectively. Serotyping and antibiotic susceptibility were performed in a central laboratory. Clinical data were abstracted from medical records. Patients were divided into 3 subgroups: pre-PCV13 (2007-2009), transitional year (2010), and post-PCV13 (2011-2013). Categorical variables were analyzed by the χ(2) test and continuous variables by the Mann--Whitney U test. RESULTS: During the study period, 173 of 1207 episodes (14%) of invasive pneumococcal disease were identified as PM; 76 of 645 (12%) were during 2007-2009 and 69 of 394 (18%) during 2011-2013 (50% increase; P = .03). The proportion of PCV13 serotype cases decreased from 54% in 2007-2009 to 27% in 2011-2013 (P = .001). Non-PCV13 serotype cases represented 73% of the isolates in 2011-2013. Isolates with ceftriaxone minimum inhibitory concentration ≥ 1 µg/mL decreased (13% to 3%) from 2007-2009 to 2011-2013 (P = .03). No significant differences were identified for hospital course or outcome, with the exception that a greater proportion of patients had subdural empyema and hemiparesis in 2011-2013. CONCLUSIONS: After the introduction of PCV13, the number of cases of PM in children remained unchanged compared with 2007-2009, although the proportion of PCV13 serotypes decreased significantly. Serotype 19A continued to be the most common serotype in 2011-2013. Antibiotic resistance decreased significantly. Morbidity and case-fatality rate due to PM remain substantial.

Changes in Streptococcus pneumoniae serotype 19A invasive infections in children from 1993 to 2011.

Among 594 Streptococcus pneumoniae serotype 19A invasive pneumococcal disease (IPD) isolates collected from 1993 to 2011, we identified 85 sequence types by multilocus sequence typing. CC320 was associated with multidrug resistance and reduced susceptibility to penicillin and ceftriaxone and still predominated among declining serotype 19A IPD isolates following PCV13 introduction.

Purpura fulminans caused by community-associated methicillin-resistant Staphylococcus aureus.

Sepsis-induced purpura fulminans is a rare but life-threatening condition characterized by rapidly progressive hemorrhagic infarction of the skin due to dermal vascular thrombosis resulting in tissue loss and severe scarring. Although most commonly related to meningococcal or invasive group A streptococcal disease, it may also be caused by several other bacterial or viral pathogens including Pneumococcus and Varicella. Purpura fulminans associated with Staphylococcus aureus sepsis is rare but has been reported in adults. However, the syndrome is very unusual in children, and to our knowledge, only 2 cases of staphylococcal purpura fulminans have been reported in children, both due to methicillin-susceptible S aureus in the United Kingdom. We report the first well-described case of purpura fulminans due to community-associated methicillin-resistant S aureus in a child.

Decrease in Pediatric Invasive Pneumococcal Disease During the COVID-19 Pandemic.

Measures to limit SARS-CoV-2 transmission in 2020 reduced other viral infections. Among 7 US children's hospitals, invasive pneumococcal disease cumulative incidence decreased by 46% in 2020 vs 2017-2019. Limited droplet transmission of pneumococci and preceding viral pathogens may be responsible.

Increase in prevalence of Streptococcus pneumoniae serotype 6C at Eight Children's Hospitals in the United States from 1993 to 2009.

Streptococcus pneumoniae serotype 6C, which was described in 2007, causes invasive disease in adults and children. We investigated the prevalence of 6C among pediatric isolates obtained from eight children's hospitals in the United States. S. pneumoniae isolates were identified from a prospective multicenter study (1993 to 2009). Fifty-seven serotype 6C isolates were identified by multiplex PCR and/or Quellung reaction. Five were isolated before 2000, and the prevalence increased over time (P < 0.000001). The median patient age was 2.1 years (range, 0.2 to 22.5 years). Clinical presentations included bacteremia (n = 24), meningitis (n = 7), pneumonia (n = 4), abscess/wound (n = 3), mastoiditis (n = 2), cellulitis (n = 2), peritonitis (n = 1), septic arthritis (n = 1), otitis media (n = 10), and sinusitis (n = 3). By broth microdilution, 43/44 invasive serotype 6C isolates were susceptible to penicillin (median MIC, 0.015 µg/ml; range, 0.008 to 2 µg/ml); all were susceptible to ceftriaxone (median MIC, 0.015 µg/ml; range, 0.008 to 1 µg/ml). By disk diffusion, 16/44 invasive isolates (36%) were nonsusceptible to erythromycin, 19 isolates (43%) were nonsusceptible to trimethoprim-sulfamethoxazole (TMP-SMX), and all isolates were clindamycin susceptible. Multilocus sequence typing (MLST) revealed 24 sequence types (STs); 9 were new to the MLST database. The two main clonal clusters (CCs) were ST473 and single-locus variants (SLVs) (n = 13) and ST1292 and SLVs (n = 23). ST1292 and SLVs had decreased antibiotic susceptibility. Serotype 6C causes disease in children in the United States. Emerging CC1292 expressed TMP-SMX resistance and decreased susceptibility to penicillin and ceftriaxone. Continued surveillance is needed to monitor changes in serotype prevalence and possible emergence of antibiotic resistance in pediatric pneumococcal disease.

Invasive Pneumococcal Disease in Children's Hospitals: 2014-2017.

BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) was licensed in the United States in 2010. We describe invasive pneumococcal disease (IPD) in children at 8 children's hospitals in the US from 2014 to 2017. METHODS: Children with IPD occurring from 2014 to 2017 were identified from a prospective study. Demographic and clinical data, including results of any immune evaluation along with the number and dates of previous pneumococcal conjugate vaccines administered, were recorded on case report forms. Isolate serotypes were determined in a central laboratory. Pneumococcal conjugate vaccine doses were counted if IPD occurred ≥2 weeks after a dose. RESULTS: PCV13 serotypes accounted for 23.9% (115 out of 482) of IPD isolates from 2014 to 2017. Serotypes 3, 19A, and 19F accounted for 91% of PCV13 serotypes. The most common non-PCV13 serotypes were 35B, 23B, 33F, and 22F. An underlying condition was significantly (P < .0001) more common in children with IPD due to non-PCV13 serotypes (200 out of 367, 54.5%) than for children with PCV13 serotypes (27 out of 115, 23.5%). An immune evaluation was undertaken in 28 children who received ≥2 PCV13 doses before IPD caused by a PCV13 serotype. Only 1 was found to have an immunodeficiency. CONCLUSIONS: PCV13 serotypes (especially serotypes 3, 19A, and 19F) continue to account for nearly a quarter of IPD in US children 4 to 7 years after PCV13 was introduced. Underlying conditions are more common in children with non-PCV13 serotype IPD. Immune evaluations in otherwise healthy children with PCV13 serotype IPD despite receiving ≥2 PCV13 doses did not identify an immunodeficiency.

Pneumocystis Jirovecii Pneumonia During Sirolimus Therapy for Kaposiform Hemangioendothelioma.

Sirolimus is an effective therapy for children with kaposiform hemangioendothelioma with or without the Kasabach-Merritt phenomenon. We report the case of a child with kaposiform hemangioendothelioma and the Kasabach-Merritt phenomenon who developed Pneumocystis carinii pneumonia (PCP) while on sirolimus and a prednisolone taper, after lack of adequate response to prednisolone, propranolol, and vincristine. He had a prompt positive clinical and laboratory response to sirolimus, but 4 weeks after starting it, at the age of 4 months, he developed PCP. This led to respiratory failure, which required extracorporeal membrane oxygenation. Sirolimus was temporarily discontinued, and he was successfully treated for PCP with sulfamethoxazole-trimethoprim and methylprednisolone. He was restarted on sirolimus 3 weeks after discharge and given sulfamethoxazole-trimethoprim prophylaxis. At the age of 22 months, while still on sirolimus, the lesion continued to improve with test results revealing stable hemoglobin and platelet counts. PCP is a rare but life-threatening side effect of sirolimus therapy, especially in the setting of concurrent steroid treatment. Pneumocystis prophylaxis should be considered for patients receiving sirolimus.

Invasive Pneumococcal Disease in Infants Aged 0-60 Days in the United States in the 13-Valent Pneumococcal Conjugate Vaccine Era.

We identified 53 infants aged 0-60 days with invasive pneumococcal disease (IPD) at 8 children's hospitals in the United States (2005-2015). After the introduction of 13-valent pneumococcal conjugate vaccine (PCV13), IPD caused by PCV13 serotypes decreased ~30% providing some evidence of indirect protection. However, approximately 60% of IPD was still caused by PCV13 serotypes.

Recurrent systemic pneumococcal disease in children.

BACKGROUND: Recurrent systemic pneumococcal infection usually occurs in immunocompromised patients and patients with underlying conditions. METHODS: Between 1993 and 2006, investigators at 8 pediatric hospitals prospectively identified cases of invasive pneumococcal disease (IPD) and retrospectively documented demographics and clinical information. Antibiotic susceptibility was determined for penicillin and ceftriaxone by microbroth dilution. Isolates were serotyped and molecular relatedness determined using pulse field gel electrophoresis (PFGE). RESULTS: Four thousand sixty-seven children were diagnosed with IPD over 12.3 years. One hundred and 8 episodes of recurrent disease were seen in 90 children (2.6%); 75 experienced 2 infections, 12 experienced 3 infections and 3 experienced 4 infections. Fourteen of the 15 children with >2 episodes of infection had underlying conditions. The mean duration between 1st and 2nd infection was 22.9 weeks for children with no known underlying condition and 43.0 weeks for children with an underlying condition (P = 0.001). Seventy episodes of IPD among the 90 patients were caused by a different serotype or a different genotype as demonstrated by the PFGE. Sixteen children had intervals <30 days between infections; 7 were caused by different strains. CONCLUSIONS: Approximately 80% of the children with recurrent invasive pneumococcal disease had underlying conditions. Seven of 16 children with recurrent infection <30 days apart were caused by acquisition of a new strain. Relapse of infection requires documentation that the pneumococcal isolates are not only the same serotype but also have the same PFGE patterns.

Orbital cellulitis in children.

BACKGROUND: To review the epidemiology and management of orbital cellulitis in children. METHODS: The medical records of children < or = 18 years old and hospitalized from June 1, 1992, through May 31, 2002, at the Brenner Children's Hospital, with a discharge ICD-9 code indicating a diagnosis of orbital cellulitis and confirmed by computed tomography scan were reviewed. A literature search for additional studies for systematic review was also conducted. RESULTS: Forty-one children with orbital cellulitis were identified. The mean age was 7.5 years (range, 10 months to 16 years), and 30 (73%) were male (male:female ratio = 2.7). All cases of orbital cellulitis were associated with sinusitis; ethmoid sinusitis was present in 40 (98%) patients. Proptosis and/or ophthalmoplegia was documented in 30 (73%), and 34 (83%) had subperiosteal and/or orbital abscesses. Twenty-nine (71%) had surgical drainage and 12 (29%) received antibiotic therapy only. The mean duration of hospitalization was 5.8 days. The mean duration of antibiotic therapy was 21 days. CONCLUSIONS: Orbital cellulitis occurs throughout childhood and in similar frequency among younger and older children. It is twice as common among males as females. Selected cases of orbital cellulitis, including many with subperiosteal abscess, can be treated successfully without surgical drainage.

Safety and immunogenicity of palivizumab (Synagis) administered for two seasons.

To evaluate the safety and immunogenicity of palivizumab, 55 children who received palivizumab in the IMpact-RSV trial received 5 monthly doses of 15 mg/kg palivizumab (Synagis) during the subsequent year. The single child with an antipalivizumab titer of >1/40 had no associated serious adverse events and had expected serum palivizumab trough concentrations. Second year palivizumab prophylaxis was safe and well-tolerated.

Pneumococcal endocarditis in children.

Endocarditis due to Streptococcus pneumoniae is unusual in children, accounting for 3%-7% of all cases of childhood endocarditis. The US Pediatric Multicenter Pneumococcal Surveillance Group has prospectively identified patients with invasive disease at 8 children's hospitals. During the period of 1 September 1993 through 28 February 2003, a total of 11 children with pneumococcal endocarditis were seen. Seven (64%) were 3-36 months old; 8 (73%) were boys. Ten (91%) had preexisting structural heart disease; 5 had undergone previous heart surgery. Concomitant sites of infection were noted in 6 patients (55%), including 3 patients with meningitis. One patient (9%) died during hospitalization, and 5 others (45%) experienced serious complications. Only 2 patients remained hospitalized for their entire course of parenteral antibiotic therapy. Eight of 10 pneumococcal isolates tested were vaccine or vaccine-related serotypes included in the currently licensed 7-valent conjugated pneumococcal vaccine. Pneumococcal endocarditis in children is unusual but often has serious complications.

Six year multicenter surveillance of invasive pneumococcal infections in children.

OBJECTIVE: Monitor clinical and microbiologic features including antimicrobial susceptibility of invasive pneumococcal infections among children. DESIGN: A 6-year (September, 1993, through August, 1999) prospective surveillance study of all invasive pneumococcal infections in children. PATIENTS: Infants and children cared for at eight children's hospitals in the United States with culture-proved invasive pneumococcal infection. RESULTS: During the 6-year period 2581 episodes of invasive pneumococcal infection occurred in 2498 children. Underlying conditions were present in 29% of the children. Of children without an underlying condition, 15% of the total infections occurred in those 25 to 60 months old. As the ages of the children advanced the proportion of cases classified as bacteremia declined, whereas the proportion classified as pneumonia increased. Also, as the ages of the children increased the proportion of isolates in serotypes/serogroups 1, 3 and 23 increased. whereas the proportion for serotype 14 diminished. During the 6 years of the study, there was a significant increase in the percentage of isolates intermediate or resistant to penicillin (P < 0.000001) or intermediate to ceftriaxone (P < 0.002). By the sixth year of the study, 37 and 11% of the isolates were nonsusceptible to penicillin or ceftriaxone, respectively. Antibiotic use in the 30 days before diagnosis of systemic pneumococcal infection occurred in 30 to 35% of the children for each of the 6 years. The overall case-fatality rate for children with systemic pneumococcal infection was 1.56%. Mortality was greatest in children >60 months old and in those with underlying conditions; mortality was not related to antibiotic susceptibility. CONCLUSIONS: The percentage of pneumococcal isolates recovered from children with systemic infection which were intermediate for penicillin or ceftriaxone or resistant to penicillin increased steadily during the 6-year period. There was also a trend toward increasing rates of resistance to ceftriaxone. The age and serogroup/serotype distributions of our patients support the recommendations to consider administration of the seven valent pneumococcal conjugate vaccine for all children 24 to 59 months old, with special consideration for selected groups.

Invasive pneumococcal infections in children with asplenia.

BACKGROUND: Asplenia is associated with an increased risk of infections caused by Streptococcus pneumoniae. Overwhelming infection can be fulminate and lead to a fatal outcome. OBJECTIVE: To review the epidemiology and clinical course of invasive S. pneumoniae infections in children with asplenia before the release of the conjugate pneumococcal vaccine. METHODS: Children with S. pneumoniae infections from eight children's hospitals in the US were identified prospectively from September, 1993, to August, 1999. Further demographic, medical and microbiologic information was gathered retrospectively from the charts of patients with asplenia. RESULTS: Twenty-two asplenic patients with 26 episodes of invasive S. pneumoniae were identified. This represents 1% of the 2,581 episodes of invasive S. pneumoniae infections identified in our study. Twelve had congenital asplenia (CA), and 10 had undergone surgical splenectomy. Nine of the patients with CA had associated complex congenital heart disease. The median age at first infection was 12.5 months for CA patients as compared with 69 months in children with surgical splenectomy (P < 0.001). Seventy-five percent of those eligible had received the polysaccharide pneumococcal vaccine. The most common serotypes isolated were 6B (8), 23F (7), 18C (2) and 19A (2). Antimicrobial prophylaxis had been prescribed for 82% of the study cohort. Clinical presentations of the 26 episodes included fever (22), shock (7), petechiae or purpura (7), disseminated intravascular coagulation (5) and respiratory distress (5). Clinical illness included bacteremia alone (12), meningitis alone (8), bacteremia with otitis media-sinusitis (3), bacteremia with pneumonia (2) and meningitis with osteomyelitis (1). Five of the 6 patients who died had meningitis. Three of the survivors (19%) had significant morbidity, and all of them had meningitis. Two patients had 2 episodes each, and 1 patient had 3 episodes. All but 1 of the multiple episodes was with a different serotype. Forty-six percent of isolates were nonsusceptible to penicillin, and 19% were nonsusceptible to ceftriaxone. There was no association between antimicrobial resistance and mortality. CONCLUSIONS: Invasive pneumococcal disease in patients with asplenia has a high mortality, especially in those with meningitis. Even though the new conjugate vaccine might increase protection, 19% of patients had disease caused by serotypes not included in the current heptavalent vaccine. Clinicians should continue to be aggressive in evaluating asplenic patients with unexplained fevers.

Disseminated mucormycosis in an adolescent with newly diagnosed diabetes mellitus.

We report a 16-year-old, previously healthy female who presented with disseminated mucormycosis leading to multiorgan failure and death with newly diagnosed type 1 diabetes mellitus and ketoacidosis. We review previous reported cases of mucormycosis in children with diabetes to demonstrate that this uncommon invasive infection may cause significant morbidity and mortality in this population.