About

Theoklis E Zaoutis, MD, MSCE, PhD, is an Emeritus Professor and Chair of Pediatrics (Infectious Diseases) at the University of Pennsylvania's Perelman School of Medicine. He completed his undergraduate degree in Biology at the State University of New York at Stonybrook in 1985, followed by a Master of Clinical Microbiology at Hahnemann University in 1987. He earned his MD from Jefferson Medical College of Thomas Jefferson University in 1996, and later obtained a Master’s in Clinical Epidemiology and Biostatistics from the University of Pennsylvania School of Medicine in 2005. In 2014, he completed a PhD at the National and Kapodistrian University of Athens School of Medicine. Zaoutis's research focuses on infectious diseases, clinical epidemiology, and biostatistics, with significant contributions to pediatric infectious diseases. His work includes investigations into antimicrobial stewardship, healthcare-associated infections, and the effectiveness of treatments for COVID-19. He has authored numerous publications in these areas, contributing to the advancement of pediatric infectious disease knowledge and clinical practice.

Research topics

• Medicine
• Intensive care medicine
• Immunology
• Pediatrics
• Pathology

Selected publications

• Antibiotic use in Greek Pediatric Hematology-Oncology and Bone Marrow Transplantation units

  2024-01-31

  preprint

  Background: Pediatric hematology-oncology (PHO) and bone marrow transplantation (BMT) units have high use of antimicrobials. Objectives: To survey antimicrobials used in Greek PHO and BMT units before and after an intervention involving education on the 2017 clinical practice guidelines (CPG) for the management of febrile neutropenia in children with cancer and hematopoietic stem cell transplant recipients. Methods: Antibiotic prescribing practices were prospectively recorded between June 2016 and November 2017. In December 2017, education for the CPG took place and antibiotic prescribing practices were followed for one more year. For antibiotic stewardship, days of therapy and length of therapy were calculated. Results: Five of six PHO units and the single pediatric BMT unit covering >92% of children with hematologic and oncologic diseases in Greece participated. Administration of ≥ 4 antibiotics simultaneously and of antibiotics with overlapping activity for ≥ 2 days was significantly more common in PHO units located in general compared to pediatric hospitals. Use of at least one antifungal was recorded in approximately 47% of the patients before and after the intervention. De-escalation and/or discontinuation of antibiotics on day 6 of initial treatment increased significantly from 43% to 53.5% (p=0.032). Although the number of patients requiring support in the intensive care unit for sepsis did not change, a significant drop was noted in all-cause mortality after the intervention (p=0.008). Conclusion: Our surveillance was able to accurately document the antibiotic prescribing practices of Greek PHO and BMT units. Moreover, it identified areas in immediate need for improvement in antibiotic stewardship.

  PublisherDOI

• Short-Course Therapy for Urinary Tract Infections in Children

  JAMA Pediatrics · 2023-06-26 · 48 citations

  letterOpen access1st author

  Importance: There is a paucity of pediatric-specific comparative data to guide duration of therapy recommendations in children with urinary tract infection (UTI). Objective: To compare the efficacy of standard-course and short-course therapy for children with UTI. Design, Setting, Participants: The Short Course Therapy for Urinary Tract Infections (SCOUT) randomized clinical noninferiority trial took place at outpatient clinics and emergency departments at 2 children's hospitals from May 2012, through, August 2019. Data were analyzed from January 2020, through, February 2023. Participants included children aged 2 months to 10 years with UTI exhibiting clinical improvement after 5 days of antimicrobials. Intervention: Another 5 days of antimicrobials (standard-course therapy) or 5 days of placebo (short-course therapy). Main Outcome Measures: The primary outcome, treatment failure, was defined as symptomatic UTI at or before the first follow-up visit (day 11 to 14). Secondary outcomes included UTI after the first follow-up visit, asymptomatic bacteriuria, positive urine culture, and gastrointestinal colonization with resistant organisms. Results: Analysis for the primary outcome included 664 randomized children (639 female [96%]; median age, 4 years). Among children evaluable for the primary outcome, 2 of 328 assigned to standard-course (0.6%) and 14 of 336 assigned to short-course (4.2%) had a treatment failure (absolute difference of 3.6% with upper bound 95% CI of 5.5.%). Children receiving short-course therapy were more likely to have asymptomatic bacteriuria or a positive urine culture at or by the first follow-up visit. There were no differences between groups in rates of UTI after the first follow-up visit, incidence of adverse events, or incidence of gastrointestinal colonization with resistant organisms. Conclusions and Relevance: In this randomized clinical trial, children assigned to standard-course therapy had lower rates of treatment failure than children assigned to short-course therapy. However, the low failure rate of short-course therapy suggests that it could be considered as a reasonable option for children exhibiting clinical improvement after 5 days of antimicrobial treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT01595529.

  PublisherOA PDFDOI

• Emergence and persistent spread of carbapenemase-producing Klebsiella pneumoniae high-risk clones in Greek hospitals, 2013 to 2022

  Eurosurveillance · 2023-11-23 · 45 citations

  articleOpen access

  Background Preliminary unpublished results of the survey of carbapenem- and/or colistin-resistant Enterobacterales (CCRE survey) showed the expansion of carbapenemase-producing Klebsiella pneumoniae (CPKP) sequence type (ST) 39 in 12 of 15 participating Greek hospitals in 2019. Aim We conducted a rapid survey to determine the extent of spread of CPKP high-risk clones in Greek hospitals in 2022 and compare the distribution of circulating CPKP clones in these hospitals since 2013. Methods We analysed whole genome sequences and epidemiological data of 310 K. pneumoniae isolates that were carbapenem-resistant or ‘susceptible, increased exposure’ from Greek hospitals that participated in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE, 2013–2014), in the CCRE survey (2019) and in a national follow-up survey (2022) including, for the latter, an estimation of transmission events. Results Five K. pneumoniae STs including ST258/512 (n = 101 isolates), ST11 (n = 93), ST39 (n = 56), ST147 (n = 21) and ST323 (n = 13) accounted for more than 90% of CPKP isolates in the dataset. While ST11, ST147 and ST258/512 have been detected in participating hospitals since 2013 and 2014, KPC-2-producing ST39 and ST323 emerged in 2019 and 2022, respectively. Based on the defined genetic relatedness cut-off, 44 within-hospital transmission events were identified in the 2022 survey dataset, with 12 of 15 participating hospitals having at least one within-hospital transmission event. Conclusion The recent emergence and rapid spread of new high-risk K. pneumoniae clones in the Greek healthcare system related to within-hospital transmission is of concern and highlights the need for molecular surveillance and enhanced infection prevention and control measures.

  PublisherOA PDFDOI

• Management of Neonates Born at ≤34 6/7 Weeks’ Gestation With Suspected or Proven Early-Onset Bacterial Sepsis

  American Academy of Pediatrics eBooks · 2023-02-17

  book-chapterSenior author
  PublisherDOI

• Management of Neonates Born at ≥35 0/7 Weeks’ Gestation With Suspected or Proven Early-Onset Bacterial Sepsis

  American Academy of Pediatrics eBooks · 2023-02-17

  book-chapterSenior author
  PublisherDOI

• 547. Molnupiravir and Nirmatrelvir/Ritonavir Effectiveness in Reducing the Risk for COVID-19 Disease Progression and Death

  Open Forum Infectious Diseases · 2023-11-27

  articleOpen access

  Abstract Background Molnupiravir (M) and Nirmatrelvir/Ritonavir (N/R) have been authorized for use in COVID-19 patients at high risk for severe disease. We aimed to evaluate the effectiveness of M and N/R in highly vulnerable SARS-CoV-2 patients using a retrospective cohort study design. Methods The study population consisted of SARS-CoV-2 infected non-hospitalized patients in Greece, aged 65 years or older, that received M between February 2 and March 25, 2022 and N/R between March 26 and July 20, 2022. The impact of each drug was determined via comparisons with age-matched control groups of SARS-CoV-2-positive patients who did not receive oral antiviral therapy, using as outcome (i) hospital admission with COVID-19 within 10 days after tested positive, and (ii) death from COVID-19 within 35 days from positive test. Results Overall, 4,240 M and 13,861 N/R recipients were enrolled. Administration of M significantly reduced the risk of hospitalization (Odds Ratio [OR] = 0.40, p < 0.001) and death (OR = 0.31, p < 0.001) among these patients based on data adjusted for age, previous SARS-CoV-2 infection, vaccination status, and time elapsed since the most recent vaccination. The reductions in risk were most profound among elderly patients (≥75 years old) and among those with high levels of drug adherence. Administration of N/R also resulted in significant reductions in the risk of hospitalization (OR = 0.31, p < 0.001) and death (OR = 0.28, p < 0.001). Similar to M, the impact of N/R was more substantial among elderly patients and in those with high levels of drug adherence. Conclusion N/R and M use prevented hospital admissions and death in a large real-world study of highly vulnerable patient populations. Disclosures All Authors: No reported disclosures

  PublisherOA PDFDOI

• Could federated data analysis be the catalyst accelerating the introduction of newborn genome screening for the detection of genetic disease?

  Rare Disease and Orphan Drugs Journal · 2023-09-27

  articleSenior author

  Data federation intermediated through trusted research environments can help accelerate the adoption and utilization of newborn genome screening worldwide. Data federation will protect individual datasets from unauthorized security breaches, allow analysis in situ , and bypass the need for cumbersome data sharing agreements between parties. Finally, data federation could accelerate the adoption of new therapies for rare genetic diseases with the use of synthetic clinical trials.

  PublisherDOI

• 2488. Healthcare-associated infections in acute care hospitals in Greece, results of the third Point Prevalence Survey, April – December 2022

  Open Forum Infectious Diseases · 2023-11-27

  articleOpen accessSenior author

  Abstract Background The burden of healthcare-associated infections (HAIs) in European acute care hospitals is estimated through periodic Point Prevalence Studies (PPS) coordinated by European Centre for Disease Prevention and Control (ECDC). In 2016, Greece had the highest HAI prevalence among European countries (10%). The current PPS aimed to estimate the prevalence of HAIs among inpatients, especially in the context of COVID-19 pandemic. Methods A cross-sectional study was conducted between April and December 2022, according to ECDC PPS protocol v.6.1, in a representative sample of 50 Greek hospitals across all country regions. Patients admitted in wards before 8.00 am of the study day were screened for inclusion. Infection control teams collected hospital characteristics (e.g., total beds, infection control markers), wards (specialty, bed occupancy) and active HAIs (type, origin, microbiological results). Active HAIs included present HAIs or past HAIs that are still being treated. ECDC HelicsWin.Net software v.4.4.0, was used for data entry and analysis. Results Overall, 12.1% inpatients (1,175 of a total 9,707) had at least one active HAI. Among the 1,408 HAIs, the most commonly observed were lower respiratory tract infections (28.9%), bloodstream infections (20%), among which 4.6% were catheter-related, and urinary tract infections (13.1%), as shown in table 1. HAI prevalence was higher in patients of intensive care units (45.7%), compared to medical (13.5%) and surgical ones (8.2%). Laboratory data were available for 58.9% of HAIs and 1,259 microorganisms were identified. Klebsiella species (20.5%), Acinetobacter species (12.8%), P. aeruginosa (10.2%), Candida species (7.9%) and S. aureus (6.3%) were frequent isolates. Antimicrobial susceptibility patterns varied depending on the pathogen (table 2). Conclusion This study shows the increased burden of HAIs among inpatients and the emergence of difficult-to-treat pathogens in Greek hospitals. Subsequent prevalence studies will provide additional evidence regarding the trend in HAI prevalence among inpatients and support the identification of modifiable practices. The invigoration of infection control and antimicrobial stewardship programs in these settings is essential. Disclosures All Authors: No reported disclosures

  PublisherOA PDFDOI

• Adjunctive Diagnostic Studies Completed Following Detection of Candidemia in Children: Secondary Analysis of Observed Practice From a Multicenter Cohort Study Conducted by the Pediatric Fungal Network

  Journal of the Pediatric Infectious Diseases Society · 2023-08-17 · 6 citations

  articleOpen access

  BACKGROUND: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown. METHODS: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days to 17 years with invasive candidiasis (predominantly candidemia) from 2014 to 2017. Ophthalmologic examination (OE), abdominal imaging (AbdImg), echocardiogram, neuroimaging, and lumbar puncture (LP) were performed per clinician discretion. Adjunctive diagnostic studies performance and positive results were determined per episode, within 30 days from candidemia onset. Associations of aDS performance with episode characteristics were evaluated via mixed-effects logistic regression. RESULTS: In 662 pediatric candidemia episodes, 490 (74%) underwent AbdImg, 450 (68%) OE, 426 (64%) echocardiogram, 160 (24%) neuroimaging, and 76 (11%) LP; performance of each aDS per episode varied across sites up to 16-fold. Longer durations of candidemia were associated with undergoing OE, AbdImg, and echocardiogram. Immunocompromised status (58% of episodes) was associated with undergoing AbdImg (adjusted odds ratio [aOR] 2.38; 95% confidence intervals [95% CI] 1.51-3.74). Intensive care at candidemia onset (30% of episodes) was associated with undergoing echocardiogram (aOR 2.42; 95% CI 1.51-3.88). Among evaluated episodes, positive OE was reported in 15 (3%), AbdImg in 30 (6%), echocardiogram in 14 (3%), neuroimaging in 9 (6%), and LP in 3 (4%). CONCLUSIONS: Our findings show heterogeneity in practice, with some clinicians performing aDS selectively, potentially influenced by clinical factors. The low frequency of positive results suggests that targeted application of aDS is warranted.

  PublisherOA PDFDOI

• Multicenter Prospective Study of Biomarkers for Diagnosis of Invasive Candidiasis in Children and Adolescents

  Clinical Infectious Diseases · 2022-01-20 · 23 citations

  articleOpen access

  BACKGROUND: Diagnosis of invasive candidiasis (IC) relies on insensitive cultures; the relative utility of fungal biomarkers in children is unclear. METHODS: This multinational observational cohort study enrolled patients aged >120 days and <18 years with concern for IC from 1 January 2015 to 26 September 2019 at 25 centers. Blood collected at onset of symptoms was tested using T2Candida, Fungitell (1→3)-β-D-glucan, Platelia Candida Antigen (Ag) Plus, and Platelia Candida Antibody (Ab) Plus assays. Operating characteristics were determined for each biomarker, and assays meeting a defined threshold considered in combination. Sterile site cultures were the reference standard. RESULTS: Five hundred participants were enrolled at 22 centers in 3 countries, and IC was diagnosed in 13 (2.6%). Thirteen additional blood specimens were collected and successfully spiked with Candida species, to achieve a 5.0% event rate. Valid T2Candida, Fungitell, Platelia Candida Ag Plus, and Platelia Candida Ab Plus assay results were available for 438, 467, 473, and 473 specimens, respectively. Operating characteristics for T2Candida were most optimal for detecting IC due to any Candida species, with results as follows: sensitivity, 80.0% (95% confidence interval, 59.3%-93.2%), specificity 97.1% (95.0%-98.5%), positive predictive value, 62.5% (43.7%-78.9%), and negative predictive value, 98.8% (97.2%-99.6%). Only T2Candida and Platelia Candida Ag Plus assays met the threshold for combination testing. Positive result for either yielded the following results: sensitivity, 86.4% (95% confidence interval, 65.1%- 97.1%); specificity, 94.7% (92.0%-96.7%); positive predictive value, 47.5% (31.5%-63.9%); and negative predictive value, 99.2% (97.7%-99.8%). CONCLUSIONS: T2Candida alone or in combination with Platelia Candida Ag Plus may be beneficial for rapid detection of Candida species in children with concern for IC. CLINICAL TRIALS REGISTRATION: NCT02220790.

  PublisherOA PDFDOI

Recent grants

• NIH Grant K23AI062975

  NIH · $666k · 2010

• Multi-center studies to improve diagnosis and treatment of pediatric candidiasis

  NIH · $2.9M · 2013–2019

Frequent coauthors

• Susan Coffin

  Children's Hospital of Philadelphia

  231 shared

• Jeffrey S. Gerber

  Children's Hospital of Philadelphia

  163 shared

• Brian T. Fisher

  University of Pennsylvania

  160 shared

• Priya A. Prasad

  University of California, San Francisco

  96 shared

• William J. Steinbach

  96 shared

• Lillian Sung

  Hospital for Sick Children

  70 shared

• David C. Naftel

  University of Alabama at Birmingham

  65 shared

• Anne I. Dipchand

  University of Toronto

  65 shared

Awards & honors

• Emeritus Professor CE of Pediatrics (Infectious Diseases)
• Selected Publications