Effect of the COVID-19 pandemic on the pediatric infectious disease landscape.

This narrative review aims to present an overview of the COVID-19 pandemic's effects on the landscape of pediatric infectious diseases. While COVID-19 generally results in mild symptoms and a favorable prognosis in children, the pandemic brought forth significant consequences. These included persistent symptoms among infected children ("long COVID"), a profound transformation in healthcare utilization (notably through the widespread adoption of telemedicine), and the implementation of optimization strategies within healthcare settings. Furthermore, the pandemic resulted in alterations in the circulation patterns of respiratory pathogens, including influenza, RSV, and Streptococcus pneumoniae. The possible reasons for those changes are discussed in this review. COVID-19 effect was not limited to respiratory infectious diseases, as other diseases, including urinary tract and gastrointestinal infections, have displayed decreased transmission rates, likely attributable to heightened hygiene measures and shifts in care-seeking behaviors. Finally, the disruption of routine childhood vaccination programs has resulted in reduced immunization coverage and an upsurge in vaccine hesitancy. In addition, the pandemic was associated with issues of antibiotic misuse and over-prescription.     Conclusion: In conclusion, the COVID-19 pandemic has left a profound and multifaceted impact on the landscape of pediatric infectious diseases, ranging from the emergence of "long COVID" in children to significant changes in healthcare delivery, altered circulation patterns of various pathogens, and concerning disruptions in vaccination programs and antibiotic usage. What is Known: • COVID-19 usually presents with mild symptoms in children, although severe and late manifestations are possible. • The pandemic resulted in a dramatically increased use of health care services, as well as alterations in the circulation patterns of respiratory pathogens, decreased rates of other, non-respiratory, infections, disruption of routine childhood vaccination programs, and antibiotic misuse. What is New: • Possible strategies to tackle future outbreaks are presented, including changes in health care services utilization, implementation of updated vaccine programs and antibiotic stewardship protocols. • The decline in RSV and influenza circulation during COVID-19 was probably not primarily related to NPI measures, and rather related to other, non-NPI measures implementation, including specific pathogen-host interactions on the level of the biological niche (the nasopharynx).

Impact of the COVID-19 era on clinical presentation, management and microbiology in paediatric peritonsillar abscess: A case-control study.

OBJECTIVES: Peritonsillar abscess (PTA) is the most common soft-tissue infection of the head and neck. This potential complication of tonsillitis has demonstrated unique microbial trends during the COVID-19 pandemic. This era has resulted in a major shift in the hygiene and social habits of the general population, which has resulted in changes in the presentation, management and microbiology of several infectious diseases. To date, the impact of COVID 19 on PTA microbiology and clinical presentation in the paediatric population has yet to be investigated. DESIGN: Retrospective chart review comparing all cases of paediatric (age 0-18) PTA in an academic tertiary centre during the COVID-19 pandemic (03/2020-02/2022) and compared them to two control groups: pre-COVID (03/2018-02/2020) and post-COVID (03/2022-03/2023). All patients were treated with either needle aspiration, incision and drainage or both means in addition to intravenous antibiotics. SETTING: A large Ear Nose and Throat department in a tertiary referral center. PARTICIPANTS: Consecutive children aged 18 years or under, admitted with a diagnosis of Peritonsillar abscess. MAIN OUTCOME MEASURES: We analyzed the clinical and microbiologcal features of all cases of pediatric peritonsillar abscess during the COVID-19 era (03/2020-02/2022) and compared them to a pre and post control cases. RESULTS: A total of 96 PTA cases were included (35 pre-COVID, 35 COVID and 26 post-COVID). The means of procedural treatment shifted in favour of incision and drainage versus needle aspiration during the COVID era. The length of hospitalisation increased during the COVID era (3.6 days vs. 2.1 and 3.1 pre and post-COVID respectively, p < .001). No other notable differences in the clinical and demographic features were found between the three eras. The COVID-19 era saw an increase in Fusobacterium (37.1% vs. 8.6% and 24% pre and post-COVID, respectively; p = .008) and Streptococcus Anginosus (31.4% vs. 5.7% and 7.7% pre and post-COVID, respectively; p = .007) species isolation. CONCLUSIONS: The COVID-19 pandemic did not seem to impact the clinical presentation of paediatric PTA yet resulted in a change in microbiological pathogens. The choice of I&D as a means to shorten hospital stay during the pandemic may have led to an actual increase in hospital stay, suggesting that NA may be the preferred management approach.

Dynamics of Pediatric Antibiotic Use Differ between High- and Low-Prescribing Clinics after Pneumococcal Conjugate Vaccines.

OBJECTIVE: To compare dispensed oral antibiotic prescription rates (DAPRs) after implementation of pneumococcal conjugate vaccine (PCV) in high antibiotic-prescribing clinics (HPC) with low antibiotic-prescribing clinics (LPC) in 2 distinct ethnic groups of children (Jewish and Bedouin children) <5 years of age. METHODS: Clinics with ≥50 insured children, active both pre-PCV (2005-2009) and post-PCV (2010-2018) implementation, were included. HPC and LPC were defined by DAPRs above or below the median in each age and ethnic group. Monthly dispensed antibiotic prescription rate (DAPR) trends (adjusted for age and ethnicity) were calculated using interrupted time series. Mean yearly incidence rate-ratios (late PCV13 vs pre-PCV) were calculated. RESULTS: Bedouin HPC had the highest pre-PCV overall-DAPR per 1000 child-years ± SD (2520.4 ± 121.2), followed by Jewish HPC (1885.5 ± 47.6), Bedouin LPC (1314.8 ± 81.6), and Jewish LPC (996.0 ± 19.6). Shortly after PCV implementation, all DAPRs and amoxicillin/amoxicillin-clavulanate DAPRs declined in all groups except Jewish LPC, stabilizing within 4-5 years post-PCV. The rates and magnitudes of declines were directly proportional to the pre-PCV DAPR magnitudes, achieving near-complete closure of the pre-PCV DAPR gaps between the 4 groups (rates during late-PCV13 ranging from 1649.4 ± 23.5 [Bedouin HPC] to 1200.3 ± 72.4 [Jewish LPC]). CONCLUSIONS: PCVs are a powerful tool in reducing outpatient antibiotic consumption among young children, especially in HPC, resulting in partial closure of DAPR gap between HPC and LPC. The higher impact on HPC suggests that PCV-associated declines of respiratory disease may strongly contribute to a judicious antibiotic approach in clinics with high antibiotic consumption.

Dynamics of invasive pneumococcal disease in infants < 2 years old following PCV7/13 implementation using two infant and a booster dose schedule: evidence for indirect protection of young infants, Israel, 2004 to 2019.

BackgroundPneumococcal conjugated vaccine (PCV)7 and PCV13 programmes started in Israel from July 2009 and November 2010 respectively, with a 2+1 schedule (one dose at 2 months old, one at 4 months old, and a booster dose at 12 months old). Thereafter, invasive pneumococcal disease (IPD) rates substantially declined in children. Uptake of all three doses in < 2-year-olds since 2012 is > 90%. For still incompletely vaccinated infants (≤ 12 months old), how well the PCV 2+1 programme shields from IPD is not fully resolved.AimTo assess the adequacy of protection conferred by the 2+1 schedule PCV vaccination programme, particularly among incompletely-vaccinated infants.MethodsThis was a population-based, prospective, nationwide active IPD surveillance study in Israel, 2004-2019, in children < 24 months old. We estimated annual incidence rates (IR) of overall IPD, IPD caused by PCV13 serotypes (VT13), and non-PCV13 serotypes (NVT13). Annual IPD IRs were stratified by age: < 4 months (receiving ≤ 1 dose), 4-6 months (immediately post dose 2), 7-12 months (a few months post dose 2), and 13-23 months (post dose 3). Late-PCV (2004-2008) to pre-PCV13 (2016-2019) mean annual IR ratios (IRRs) were calculated.Results2,569 IPD episodes were recorded. VT13 decreased > 90% in all age groups, while NVT13 seemed to increase. All-IPD rates declined in all age groups by 56-70%. The 2+1 schedule impact on 7-12-month-old infants (pre-booster) was similar to that on 13-23-month-old children (post booster), with PCV13 IPD reductions of 97% and 98%, respectively.ConclusionsIndirect (herd) protection of infants, including < 4 month-olds with ≤ 1 PCV dose, was achieved by the 2+1 PCV schedule programme which thus seems adequate.

Dynamics of Invasive Pneumococcal Disease in Israel in Children and Adults in the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Era: A Nationwide Prospective Surveillance.

BACKGROUND: Following 13-valent pneumococcal conjugate vaccine (PCV13) implementation in infants worldwide, overall and vaccine-type invasive pneumococcal disease (IPD) rates declined in children, with variable indirect impact on adults. METHODS: A population-based, prospective, nationwide active surveillance of IPD in Israel, 2004-2019 (for adults ≥18 years, 2009-2019). The 7-valent PCV (PCV7)/PCV13 were implemented in Israel in July 2009/November 2010, respectively, with >90% uptake in children <2 years. The 23-valent pneumococcal polysaccharide vaccine (PPV-23) uptake among those >65 years was ~75%. For pre-PCV episodes with missing serotype, extrapolations were applied. Overall, PCV13 serotypes (VT13) and non-VT13 (NVT) incidence rate ratios (IRRs) comparing pre-PCV (2004-2008), early-PCV (2009-2011), and late-PCV13 (2016-2019) periods were calculated for different age groups. RESULTS: Overall, 8614 IPD cases were recorded. IPD rates declined by 67% in children <5 and 5-17 years, comparing late-PCV13 versus pre-PCV periods (IRR [95% CI]: .33 [.27-.40] and .33 [.21-.50], respectively). For adults, comparing late-PCV13 with early-PCV periods, rates significantly declined by 53% in those aged 18-44, while rates did not decline significantly in other age groups. VT13 rates significantly declined in all ages, with decline rates ranging between 94% in children <5 years and 60% in adults ≥85 years. NVT rates significantly increased in <5-, 50-64-, and ≥65-year age groups. In the late-PCV13 period, serotypes 3, 14, and 19A remained the predominant VT13, while serotypes 8 and 12F emerged as predominant NVTs. CONCLUSIONS: Continuous monitoring of circulating serotypes in all ages demonstrated direct and indirect PCV effects, which are essential for the development of new vaccination strategies.

Decline in Pneumococcal Disease in Young Children During the Coronavirus Disease 2019 (COVID-19) Pandemic in Israel Associated With Suppression of Seasonal Respiratory Viruses, Despite Persistent Pneumococcal Carriage: A Prospective Cohort Study.

BACKGROUND: The incidence of invasive pneumococcal disease (IPD) declined during the COVID-19 pandemic. Previous studies hypothesized that this was due to reduced pneumococcal transmission resulting from nonpharmaceutical interventions. We used multiple ongoing cohort surveillance projects in children <5 years to test this hypothesis. METHODS: The first SARS-CoV-2 cases were detected in February 2020, resulting in a full lockdown, followed by several partial restrictions. Data from ongoing surveillance projects captured the incidence dynamics of community-acquired alveolar pneumonia (CAAP), nonalveolar lower respiratory infections necessitating chest X-rays (NA-LRIs), nasopharyngeal pneumococcal carriage in nonrespiratory visits, nasopharyngeal respiratory virus detection (by polymerase chain reaction), and nationwide IPD. Monthly rates (January 2020 through February 2021 vs mean monthly rates 2016-2019 [expected rates]) adjusted for age and ethnicity were compared. RESULTS: CAAP and bacteremic pneumococcal pneumonia were strongly reduced (incidence rate ratios [IRRs]: .07 and .19, respectively); NA-LRIs and nonpneumonia IPD were also reduced by a lesser magnitude (IRRs: .46 and .42, respectively). In contrast, pneumococcal carriage prevalence was only slightly reduced, and density of colonization and pneumococcal serotype distributions were similar to previous years. The decline in pneumococcus-associated disease was temporally associated with a full suppression of respiratory syncytial virus, influenza viruses, and human metapneumovirus, often implicated as co-pathogens with pneumococcus. In contrast, adenovirus, rhinovirus, and parainfluenza activities were within or above expected levels. CONCLUSIONS: Reductions in pneumococcal and pneumococcus-associated diseases occurring during the COVID-19 pandemic in Israel were not predominantly related to reduced pneumococcal carriage and density but were strongly associated with the disappearance of specific respiratory viruses.

Disproportionate reduction in respiratory vs. non-respiratory outpatient clinic visits and antibiotic use in children during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic led to improved hygiene and reduced social encounters. Near elimination of the activity of respiratory syncytial virus and influenza viruses were observed, worldwide. Therefore, we assessed the rates of pediatric outpatient clinic visits and medications prescribed at those visits during the coronavirus disease 2019 (COVID-19) pandemic and pre-COVID-19 period (2016-2019). METHODS: Monthly and annual incidence rates for respiratory and non-respiratory diagnoses and dispensed prescription rates were calculated. Acute gastroenteritis (AGE) visits were analyzed separately since the mode of transmission is influenced by hygiene and social distancing. RESULTS: Overall, 5,588,702 visits were recorded. Respiratory and AGE visits declined by 49.9% and 47.3% comparing the COVID-19 and pre-COVID-19 periods. The respective rate reductions for urinary tract infections, trauma, and skin and soft tissue infections were 18.2%, 19.9%, and 21.8%. Epilepsy visits increased by 8.2%. Overall visits rates declined by 21.6%. Dispensed prescription rates of antibiotics and non-antibiotics respiratory medications declined by 49.3% and 44.4%, respectively. The respective declines for non-respiratory antibiotics and non-antibiotics were 15.1% and 0.2%. Clinic visits and prescription rates reductions were highest in April-May, following the first lockdown in Israel. CONCLUSIONS: COVID-19 pandemic resulted in a substantial reduction in respiratory outpatient clinic visits and dispensed respiratory drugs, with only a mild reduction seen for non-respiratory visits. These trends were probably driven by COVID-19 mitigation measures and by the profound disruption to non-SARS COV-2 respiratory virus activity.

A Prospective, Population-based Study to Determine the Incidence and Bacteriology of Bacterial Conjunctivitis in Children <2 Years of Age Following 7-Valent and 13-Valent Pneumococcal Conjugate Vaccine Sequential Implementation.

BACKGROUND: Bacterial conjunctivitis is most commonly caused by nontypeable Haemophilus influenzae (NTHi), followed by Streptococcus pneumoniae. No population-based data on the impact of pneumococcal conjugate vaccines (PCVs) on the incidence of bacterial conjunctivitis have been published. We assessed rate dynamics of overall, pneumococcal, and NTHi conjunctivitis in children aged 2-23 months in southern Israel before and after PCV implementation. METHODS: This is a 12-year prospective, population-based surveillance, from July 2004 through June 2017. Our medical center serves a captive population of approximately 30 000 children < 2 years of age, and its clinical microbiology laboratory processes > 80% of all community-derived cultures, enabling incidence calculation. The 7-valent and 13-valent PCVs (PCV7 and PCV13, respectively) were implemented in the national immunization program in July 2009 and November 2010, respectively. Pneumococci, NTHi, Moraxella catarrhalis, and Streptococcus pyogenes were considered pathogens. Continuous annual incidences and incidence rate ratios comparing the PCV13 period (2015-2017) to the pre-PCV period (2004-2008) were calculated. RESULTS: Disease caused by PCV13 serotypes declined by 93%, without significant replacement with non-PCV13 serotypes. Rates of pneumococcal, NTHi, and overall culture-positive episodes declined by 59%, 41%, and 42%, respectively, while rates of culture-negative and other pathogens episodes did not change significantly. An overall reduction in all submitted culture rates of 35% was observed. This pattern was seen across all ages, including infants aged 2-5 months. CONCLUSIONS: PCV7/PCV13 implementation resulted in a marked and significant decline in pneumococcal, NTHi, and overall conjunctivitis rates in children < 2 years of age. The impact on NTHi episodes alludes to the role of pneumococcus-NTHi interaction in conjunctivitis. The impact in infants aged < 6 months suggests herd protection.

Effectiveness of the 7- and 13-Valent Pneumococcal Conjugate Vaccines Against Vaccine-Serotype Otitis Media.

BACKGROUND: Despite the demonstrated impact of pneumococcal vaccine (PCV) implementation on otitis media (OM), demonstration of real-life serotype-specific effectiveness of the 7-valent and 13-valent PCVs (PCV7 and PCV13) is lacking owing to the paucity of culture-positive cases. Furthermore, prelicensure PCV13 efficacy against OM was not studied. METHODS: The study was conducted from October 2009 to July 2013. Case patients were children aged 5-35 months with OM (mostly complex OM [recurrent/nonresponsive, spontaneously draining, chronic with effusion]) from whom middle-ear fluid culture was obtained; controls were contemporary children with rotavirus-negative gastroenteritis in a prospective population-based rotavirus surveillance, from the same age group with similar ethnic distribution and geographic location. Vaccine effectiveness (VE) was estimated as 1 minus the odds ratio using unconditional logistic regression, adjusting for time since PCV implementation, age, and ethnicity. RESULTS: A total of 223 case patients and 1370 controls were studied. Serotypes 19F and 19A together caused 56.1% of all vaccine-type (VT) OM. VE of ≥2 PCV doses in children aged 5-35 months was demonstrated as follows: PCV7 against OM due to PCV7 serotypes, 57.2% (95% confidence interval, 6.0%-80.5%); PCV13 against OM due to PCV13 serotypes, 77.4% (53.3%-92.1%); PCV13 against OM due to the 6 additional non-PCV7 serotypes 67.4% (17.6%-87.1%); PCV13 against OM due to serotype 19F, 91.3% (1.4%-99.2%); and PCV13 against OM due to serotype 3, 85.2% (23.9%-98.4%). PCV7 and PCV13 VE against OM due to serotype 19A in children aged 12-35 months was 72.4% (95% confidence interval, 6.2%-91.9%) and 94.6% (33.9%-99.6%), respectively. CONCLUSIONS: PCV7 and PCV13 were effective against complex OM caused by the targeted serotypes.

Unraveling the Impact of Pneumococcal Conjugate Vaccines on Ambulatory Antibiotic Drug Consumption in Young Children: An Interrupted Time-Series Analysis.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) reduce respiratory infections in young children, the main antibiotic consumers. Following PCV implementation, dispensed antibiotic prescription (DAP) rates in young children were expected to decline. METHODS: Computerized data on DAP for children <5 years were examined during a 13-year period (including 4 pre-PCV years). All DAPs from clinics with ≥50 insured children, active both pre- and post-PCV implementation were included. Interrupted time-series with segmented regression was applied to analyze monthly DAP rate trends, adjusted for age, ethnicity, and season. Incidence rate ratios (IRRs) of DAPs during the late PCV13 period versus 4 years pre-PCV were calculated both as absolute rate ratios (aIRRs) and relative to expected rates (rIRRs). RESULTS: Of 1 090 870 DAPs, 57% were in children <2 years. All-DAP rates peaked in the cold season. Post-PCV7/PCV13 implementation, all DAP rates abruptly and significantly declined, reaching a plateau within 5 years. This was largely driven by amoxicillin/amoxicillin-clavulanate (75% of DAPs). Age <2 years and Bedouin ethnicity were significantly associated with higher pre-PCV DAP rates but with faster and greater decline post-PCV, achieving near elimination of gaps between ages and ethnic groups. Overall reduction (95% CIs) in DAP rates per 1000 was estimated between aIRR (344.7 [370.9-358.4]) and rIRR (110.4 [96.9-123.7]) values. CONCLUSIONS: Shortly following PCV implementation, overall DAP rates showed an abrupt, steep decline, stabilizing within 5 years, in parallel to post-PCV respiratory infection trends previously described in this population, suggesting causality. The variable patterns of certain drug categories suggest additional influences beyond PCV.

A Nationwide Outbreak of Invasive Pneumococcal Disease in Israel Caused by Streptococcus pneumoniae Serotype 2.

BACKGROUND: Invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae serotype 2 (Sp2) is infrequent. Large-scale outbreaks were not been reported following pneumococcal conjugate vaccine (PCV) implementation. We describe a Sp2 IPD outbreak in Israel, in the PCV13 era, with focus on Sp2 population structure and evolutionary dynamics. METHODS: The data were derived from a population-based, nationwide active surveillance of IPD since 2009. PCV7/PCV13 vaccines were introduced in July 2009 and November 2010, respectively. Sp2 isolates were tested for antimicrobial susceptibility, multilocus sequence typing, and whole-genome sequencing (WGS) analysis. RESULTS: Overall, 170 Sp2 IPD cases were identified during 2009-2019; Sp2 increased in 2015 and caused 6% of IPD during 2015-2019, a 7-fold increase compared with 2009-2014. The outbreak was caused by a previously unreported molecular type (ST-13578), initially observed in Israel in 2014. This clone caused 88% of Sp2 during 2015-2019. ST-13578 is a single-locus variant of ST-1504, previously reported globally including in Israel. WGS analysis confirmed clonality among the ST-13578 population. Single-nucleotide polymorphism-dense regions support a hypothesis that the ST-13578 outbreak clone evolved from ST-1504 by recombination. All tested strains were penicillin-susceptible (minimum inhibitory concentration <0.06 µg/mL). The ST-13578 clone was identified almost exclusively (99%) in the Jewish population and was mainly distributed in 3 of 7 Israeli districts. The outbreak is still ongoing, although it began declining in 2017. CONCLUSIONS: To the best of our knowledge, this is the first widespread Sp2 outbreak since PCV13 introduction worldwide, caused by the emerging ST-13578 clone.

Post-13-Valent Pneumococcal Conjugate Vaccine Dynamics in Young Children of Serotypes Included in Candidate Extended-Spectrum Conjugate Vaccines.

After worldwide implementation of 10-valent and 13-valent pneumococcal conjugate vaccines (PCV10/PCV13), a 20-valent PCV (PCV20) was developed. We assessed dynamics of non-PCV13 additional PCV20 serotypes (VT20-13), compared with all other non-VT20 serotypes, in children <2 years of age in late PCV13 (2015-2017) and early PCV (2009-2011) periods. Our prospective population-based multifaceted surveillance included isolates from carriage in healthy children, children requiring chest radiography for lower respiratory tract infections (LRTIs), and children with non-LRTI illness, as well as isolates from acute conjunctivitis, otitis media (OM), and invasive pneumococcal disease (IPD). After PCV13 implementation, VT20-13 increased disproportionally in OM, IPD, and carriage in LRTI. VT20-13/non-VT20 prevalence ratio range was 0.26-1.40. VT20-13 serotypes were more frequently antimicrobial-nonsusceptible than non-VT20 serotypes. The disproportionate increase of VT20-13 in respiratory infections and IPD points to their higher disease potential compared with all other non-VT20 as a group.

Benign course and clinical features of COVID-19 in hospitalised febrile infants up to 60 days old.

AIM: Minimal data exist regarding the severity of COVID-19 in febrile infants under 60 days old. This multicentre prospective study explored the clinical course and outcomes of this hospitalised patient population, as, to date, the best approach has not been specifically addressed. METHODS: This study focused on the clinical features, laboratory parameters and outcomes of febrile infants up to 60 days old who tested positive for the virus and were hospitalised in Israel from March 2020 to January 2021. The data were extracted from a real-time prospective surveillance network for COVID-19 that includes 20 of the country's 26 hospitals. RESULTS: We identified 75 febrile young infants (60% female) with COVID-19 at a median age of 28 days (range 8-56 days). Of these, 84% had an unremarkable medical history, 29% had respiratory symptoms, and 96% had a mild illness. The Rochester criteria showed that 44% were considered at high-risk for serious bacterial infections, and we found that eight infants actually had concomitant bacterial infections. Outcomes were excellent, and no complications or fatalities were reported. CONCLUSION: The excellent outcomes of young febrile infants with COVID-19 closely resembled other respiratory viral aetiologies of fever in this age group, and there were no fatalities.

Nasopharyngeal Carriage of Invasive Pneumococcal Serotypes During Childhood Community-Acquired Alveolar Pneumonia Is Associated With Specific Clinical Presentation.

BACKGROUND: Streptococcus pneumoniae (Pnc) serotypes differ in invasive potential. We examined whether community-acquired alveolar pneumonia (CAAP) in children carrying commonly recognized pneumonia invasive pneumococcal serotypes ([PnIST] 1, 5, 7F, 14, and 19A) differs from CAAP in children carrying less invasive serotypes (non-PnIST) or no Pnc (Pnc-neg). METHODS: Children <5 years, visiting the only regional Pediatric Emergency Room, with radiologically proven CAAP were enrolled. Nasopharyngeal cultures were processed for pneumococcal isolation and serotyping. Clinical and demographic characteristics were recorded. The study was conducted before pneumococcal conjugate vaccine implementation in Israel. RESULTS: A total of 1423 CAAP episodes were recorded: PnIST, 300 (21.1%); non-PnIST, 591 (41.5%); and Pnc-neg, 532 (37.4%). After adjustment for age, ethnicity, seasonality, and previous antibiotics, the following variables were positively associated with PnIST carriage compared with both groups: temperature ≥39°C, peripheral white blood cell count ≥20 000/mm3, C-reactive protein ≥70.0 mg/L, and serum sodium <135 mEq/L. Lower oxygen saturation, viral detection, and comorbidities were negatively associated with Pn-IST carriage (odds ratios, <1.0). Differences between non-PnIST carriers and Pnc-neg groups were smaller or nonsignificant. CONCLUSIONS: Young children with CAAP carrying common PnIST had a lower proportion of comorbidities, hypoxemia, and viral detection and had more intense systemic inflammatory response than those carrying non-PnIST or not carrying Pnc.

Use of Chest Radiography Examination as a Probe for Pneumococcal Conjugate Vaccine Impact on Lower Respiratory Tract Infections in Young Children.

BACKGROUND: Community-acquired alveolar pneumonia (CAAP) is considered a bacterial disease, mainly pneumococcal. CAAP rates markedly declined following 7- and 13-valent pneumococcal conjugate vaccine (PCV) introductions worldwide. In contrast, non-CAAP lower respiratory tract infections (NA-LRIs) are generally not considered pneumococcal diseases. We assessed CAAP, NA-LRIs, and overall visits with chest radiograph (CXR) examination rates in the pediatric emergency room in southern Israel before and after PCV implementation. METHODS: This was an ongoing, prospective observational study. Our hospital serves a captive population of approximately 75 000 children aged <5 years, enabling incidence calculation. PCV7 and PCV13 were implemented in Israel in July 2009 and November 2010, respectively. All CXRs were analyzed according to the World Health Organization Standardization of Interpretation. We calculated CAAP, NA-LRI, and CXR examinations annual incidences from 2004 to 2017 and incidence rate ratios comparing the PCV13 (2014-2017) with the pre-PCV (2004-2008) periods. RESULTS: Overall, 72 746 CXR examinations were recorded: 14% CAAP and 86% NA-LRI. CAAP, NA-LRI, and CXR examination visit rates declined by 49%, 34%, and 37%, respectively. This pattern was seen in Jewish and Bedouin children (the 2 ethnically distinct populations), with steeper declines observed among Jewish children and children aged >12 months. CONCLUSIONS: PCV7/PCV13 implementation resulted in a marked decline in CAAP and overall visits with CXR examination rates in young children. Overall, approximately 14 750 hospital visits with CXR were prevented annually per 100 000 population aged <5 years. These findings suggest that although NA-LRIs are usually not considered pneumococcal, many can be prevented by PCVs.Pneumococcal conjugate vaccine (PCV7/PCV13) implementation resulted in significant declines in community-acquired alveolar pneumonia (CAAP) and overall chest radiography examination rates in young children. Although non-CAAP lower respiratory tract infections are usually not considered pneumococcal, many can be prevented by PCVs.

Substantial reduction of antibiotic-non-susceptible pneumococcal otitis media following PCV7/PCV13 sequential introduction.

BACKGROUND: In the pre-pneumococcal conjugated vaccines (PCVs) era, serotypes included in the 7/13-valent PCVs (PCV7/PCV13) caused most pneumococcal otitis media (OM) and antibiotic-non-susceptible pneumococcal OM (ANSP-OM) episodes. In southern Israel, sequential PCV7/PCV13 introduction resulted in >90% reduction of vaccine-serotype OM. OBJECTIVES: We assessed the dynamics of ANSP-OM necessitating middle ear fluid culture following PCV7/PCV13 sequential introduction in young children. METHODS: This was a prospective, population-based, active surveillance. All episodes in children <3 years old, during 2004-16, were included. Two subperiods were defined: (i) pre-PCV: 2004-08; and (ii) PCV13: 2014-16. ANSP was defined for the following antibiotics: penicillin (MIC ≥0.1 mg/L and ≥1.0 mg/L), macrolide, tetracycline, clindamycin, ceftriaxone, trimethoprim/sulfamethoxazole and chloramphenicol. MDR was defined as ANSP for ≥3 classes. RESULTS: Overall, 2270 pneumococcal OM episodes were identified. Annual overall pneumococcal, PCV13 and non-PCV13 serotype OM incidence declined by 86%, 97% and 33%, respectively, comparing pre-PCV with the PCV13 period. During 2004-08, 95% of ANSP was observed in vaccine serotypes. Incidence of penicillin (MIC ≥0.1 mg/L and ≥1.0 mg/L), macrolide, tetracycline, clindamycin, ceftriaxone and multidrug ANSP-OM declined by >90% in the PCV13 period. Rates of trimethoprim/sulfamethoxazole and chloramphenicol ANSP-OM declined by 85% and 79%, respectively. The proportions of ANSP of all pneumococcal isolates declined by ∼70% for penicillin, ceftriaxone and erythromycin; 53% for tetracycline; and 55% for MDR, versus no significant reductions observed for chloramphenicol, trimethoprim/sulfamethoxazole and clindamycin. CONCLUSIONS: PCV7/PCV13 sequential introduction resulted in rapid and substantial ANSP-OM reduction, in parallel with the near disappearance of PCV13-serotype OM and no increase in replacement disease.

Understanding the Evolution of Antibiotic-nonsusceptible Pneumococcal Nasopharyngeal Colonization Following Pneumococcal Conjugate Vaccine Implementation in Young Children.

BACKGROUND: Four main processes determine pneumococcal conjugate vaccine (PCV) antibiotic-nonsusceptible Streptococcus pneumoniae (ANSP) carriage: reduction of PCV serotypes, increase of non-PCV serotypes, potential overall reduction in carriage, and within-serotype nonsusceptibility resulting from continuous antibiotic pressure. The post-PCV implementation dynamics of these components were examined in young children from 2 distinct ethnic populations: Jewish and Bedouin. METHODS: We performed ongoing, prospective, population-based, active surveillance initiated at the time of 7- and 13-valent PCVs (PCV7; PCV13) implementation. Nasopharyngeal cultures for S. pneumoniae were obtained daily from children aged <5 years who visited the only pediatric emergency room in the district during a 6-year period (2009 to 2015). RESULTS: Of 8446 nasopharyngeal samples, 48.3% were positive (42.0% and 52.8% for Jewish and Bedouin children, respectively; P < .001). Nonsusceptibility was significantly more frequent among PCV serotypes than among non-PCV serotypes and among Bedouin children than among Jewish children. PCV serotype carriage declined by 80%, while that of non-PCV serotypes increased by 140%. The overall (all serotypes) pneumococcal carriage significantly declined (33% and 11% in Bedouin and Jewish children, respectively). Among non-PCV isolates, the proportion of ANSP significantly increased with time in both populations. As a summation of all 4 processes, ANSP carriage significantly decreased among both Bedouin and Jewish children. CONCLUSIONS: PCV impact on ANSP nasopharyngeal carriage is a dynamic, multicomponent process, highly dependent on antibiotic consumption in the community, which may result in a continuous increase in antibiotic resistance in the replacing serotypes.

Treatment Outcomes of Stenotrophomonas maltophilia Bacteremia in Critically Ill Children: A Multicenter Experience.

OBJECTIVES: Stenotrophomonas maltophilia is a gram-negative opportunistic bacterium that may cause a myriad of clinical diseases in immunocompromised individuals. We aimed to describe the clinical characteristics, risk factors, mortality, and treatment of S. maltophilia bacteremia in critically ill children, a topic on which data are sparse. DESIGN: A multicenter observational retrospective study in which medical charts of critically ill children with S. maltophilia bacteremia were reviewed between 2012 and 2017. SETTING: Data were collected from each of the four largest PICUs nationwide, allocated in tertiary medical centers to which children with complex conditions are referred regularly. PATIENTS: A total of 68 suitable cases of S. maltophilia bacteremia were retrieved and reviewed. MEASUREMENTS AND MAIN RESULTS: The total occurrence rate of S. maltophilia isolation had increased significantly during the study period (r = 0.65; p = 0.02). The crude mortality was 42%, and the attributed mortality was 18%. Significant risk factors for mortality were a longer length of hospital stay prior to infection (33 d in nonsurvivors vs 28 in survivors; p = 0.03), a nosocomial source of infection (p = 0.02), presentation with septic shock (p < 0.001), and treatment with chemotherapy (p = 0.007) or carbapenem antibiotics (p = 0.05) prior to culture retrieval. On multivariate analysis, septic shock (odds ratio, 14.6; 95% CI, 1.45-147.05; p = 0.023) and being treated with chemotherapy prior to infection (odds ratio, 5.2; 95% CI, 1.59-17.19; p = 0.006)] were associated with mortality. The combination of ciprofloxacin, trimethoprim-sulfamethoxazole, and minocycline resulted in the longest survival time (p < 0.01). CONCLUSIONS: The significant attributed mortality associated with S. maltophilia bacteremia in critically ill children calls for an aggressive therapeutic approach. The findings of this investigation favor a combination of trimethoprim-sulfamethoxazole, ciprofloxacin, and minocycline.

A retrospective study on demographic and clinical characteristics of cutaneous leishmaniasis suspected cases in southern Israel, 2013-2016: Comparison between confirmed and negative cases.

BACKGROUND & OBJECTIVES: Clinical diagnosis of cutaneous leishmaniasis (CL) may bear a high rate of false diagnosis. This study assessed CL-suspected episodes, in an attempt to differentiate confirmed CL and non-CL diagnoses. METHODS: In this retrospective, case-control study, medical files of CL-suspected episodes, tested by a biopsy for Leishmania-PCR, from 2013 to 2016, were collected and analysed statistically. RESULTS: Of 324 suspected CL episodes, 48.8% were PCR-confirmed CL (96.2% Leishmania major) and 51.2% were non-CL (57.1% bacterial infections). Overall, 59.3% episodes were in males. Mean (± SD) duration until diagnosis was 3.7 ± 7.2 months. Lesions (mean 2.9 ± 3.8 per episode) were mostly (60.8%) sampled from September through February. Ulcer, pain, itching, purulent discharge and fever were recorded in 55.2, 47, 42.9, 18.2 and 4.7% of episodes, respectively. Univariate analysis showed that male gender, multiple lesions, ulcer, >1-month duration until diagnosis, and seasonality were associated with CL. Empiric CL treatment was recorded in 63.4 and 16% of CL-confirmed and non-CL episodes, respectively (p <0.001); and was observed to be associated with Jewish ethnicity, seasonality, multiple lesions, ulcer, absence of fever and duration of >1-month until diagnosis. In multivariate analysis, seasonality (odds ratio, OR = 2.144), empiric CL treatment (OR = 5.144) and ulcer (OR = 2.459) were associated with CL. Empiric CL treatment was associated with Jewish ethnicity (OR = 2.446) and duration of >1-month until diagnosis (OR = 3.304). INTERPRETATION & CONCLUSION: CL diagnosis should be laboratory confirmed, as clinical appearance is often misleading. Seasonality, ulcer appearance and gender may aid in correct identification and treatment of CL cases.

[METHICILLIN-RESISTANT VS. METHICILLIN-SUSCEPTIBLE STAPHYLOCOCCUS AUREUS (MRSA VS. MSSA) INFECTIONS IN CHILDREN IN SOUTHERN ISRAEL].

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of morbidity. Data regarding MRSA infections in children in Israel are scarce. OBJECTIVES: We assessed MRSA prevalence, risk factors and clinical manifestations in children with Staphylococcus aureus infections in southern Israel. METHODS: Our medical center is the sole hospital in southern Israel. All medical files of Staphylococcus aureus infections during the period 2005-2015, were reviewed retrospectively. RESULTS: Overall, 1,062 SA infections (MRSA; n=164, 15%) were identified; 687 (65%) skin and soft tissue infections (SSTI), and 375 (35%) invasive infections. MRSA was significantly more common in children <5 years (18% vs. 13% in children ≥5 years), Bedouin ethnicity (19% vs. 8% in Jewish children), burns (24% vs. 15%), congenital insensitivity to pain with anhidrosis (CIPA; 90% vs. 15%) and SSTI (17% vs. 12% in invasive infections). Blood count parameters and hospital-associated vs. community-acquired infection rates were similar comparing MRSA and Methicillin-susceptible Staphylococcus aureus (MSSA). In multivariate analysis, age (odds ratio, OR=0.953), Bedouin ethnicity (OR=2.698), burns (OR=2.036) and SSTI (OR=1.674) were associated with MRSA. MRSA isolates were more frequently resistant than MSSA to clindamycin (30% vs. 14%), erythromycin (34% vs. 15%), co-trimoxazole, tetracycline, rifampicin, ciprofloxacin and gentamicin (4% vs. 0.5%, all). All isolates were vancomycin susceptible. CONCLUSIONS: MRSA infections are common in young, Bedouin children and burns, and are more commonly multidrug resistant than MSSA in our region. Our data should be used to better identify and treat children with MRSA infection.