Editorial

7 pages, 231 KiB

Open AccessEditorial

Neglected Populations Not to Be Forgotten: Tackling Antimicrobial Resistance in Neonatal Infections

by Lucia Barcellini, Ilia Bresesti and Laura Folgori

Antibiotics 2023, 12(12), 1688; https://doi.org/10.3390/antibiotics12121688 - 01 Dec 2023

Viewed by 724

Making further progress in reducing child mortality hinges on lowering the annual count of neonatal deaths; currently, this stands at 2 [...] Full article

(This article belongs to the Special Issue Tackling Antimicrobial Resistance in Neonatal Infections)

Research

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11 pages, 2336 KiB

Open AccessArticle

The Management of Neonates ≥34 Weeks’ Gestation at Risk of Early Onset Sepsis: A Pilot Study

by Maria Cristina Barbini, Simona Perniciaro, Ilia Bresesti, Laura Folgori, Lucia Barcellini, Angela Bossi and Massimo Agosti

Antibiotics 2023, 12(8), 1306; https://doi.org/10.3390/antibiotics12081306 - 10 Aug 2023

Viewed by 980

Abstract

Early onset sepsis (EOS) is a potentially fatal condition in neonates, and its correct management is still challenging for neonatologists. Early antibiotic administration in the neonatal period may carry short- and long-term risks. Neonatal EOS calculator has been recently introduced as a new [...] Read more.

Early onset sepsis (EOS) is a potentially fatal condition in neonates, and its correct management is still challenging for neonatologists. Early antibiotic administration in the neonatal period may carry short- and long-term risks. Neonatal EOS calculator has been recently introduced as a new strategy to manage infants at risk of sepsis, and has shown promising results. Methods: In this single-center observational retrospective study, 1000 neonates ≥ 34 weeks’ gestation were enrolled with the aim to evaluate our standard protocol for the management of suspected EOS compared to the EOS calculator. Outcome measures included the following: (1) incidence of EOS and (2) proportion of infants in need of sepsis evaluations and antibiotics using our standard protocol versus theoretical application of EOS calculator. Results: A total of 223/1000 infants underwent blood investigations versus 35/1000 (3.5%) if EOS calculator had been applied (p < 0.0001; k = 0.18). Furthermore, 48/1000 infants received antibiotics with our protocol versus 35/1000 with EOS calculator (p = 0.12; k = 0.58). Three infants had a positive blood culture that EOS calculator would have missed. Conclusions: In our study, EOS calculator could have reduced investigations but not antibiotic therapy. EOS calculator is an effective and promising tool, but further studies are required to improve it. Full article

(This article belongs to the Special Issue Tackling Antimicrobial Resistance in Neonatal Infections)

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16 pages, 1139 KiB

Open AccessArticle

Challenges in the Implementation of the NeoOBS Study, a Global Pragmatic Observational Cohort Study, to Investigate the Aetiology and Management of Neonatal Sepsis in the Hospital Setting

by Amy Riddell, Aislinn Cook, Nathalie Khavessian, Sally Ellis, Davide Bilardi, Erika Correia, Tomislav Kostyanev, Alessandra Nardone, Neal Russell, Tuba Vilken, Wolfgang Stohr, Bethou Adhisivam, Iana Rosa Alves de Moraes, Nawshad Uddin Ahmed, Adrie Bekker, Eitan Naaman Berezin, Suppawat Boonkasidecha, Cristina G. Carvalheiro, Prachi Chauhan, Sara Chiurchiù, Elisavet Chorafa, Angela Dramowski, Madhusudhan DS, Jinxing Feng, Shengnan Jia, Yuan Kong, Mary Kyohere, Angeliki Kontou, Sorasak Lochindarat, Maia De Luca, Aripfani Mphaphuli, Marisa M. Mussi-Pinhata, Sheila Murunga, Firdose Lambey Nakwa, Sushma Nangia, Erinah Nassolo, Ngoc Thi Bin Hoang, Christina W. Obiero, Linus Olson, Wang Ping, Nishad Plakkal, Priyanka Prasad, Kanchana Preedisripipat, Sheikh Wasik Rahman, Tiffany Seef, Pra-ornsuda Sukrakanchana, Reenu Thomas, Zhang Yu, Qiaoru Zhang, A. Sarah Walker, Julia Bielicki, Paul T. Heath, Michael Sharland and Tatiana Munera-Huertas Show full author list Hide full author list

Antibiotics 2023, 12(5), 923; https://doi.org/10.3390/antibiotics12050923 - 17 May 2023

Cited by 1 | Viewed by 2254

Abstract

Neonatal sepsis is a significant cause of mortality and morbidity in low- and middle-income countries. To deliver high-quality data studies and inform future trials, it is crucial to understand the challenges encountered when managing global multi-centre research studies and to identify solutions that [...] Read more.

Neonatal sepsis is a significant cause of mortality and morbidity in low- and middle-income countries. To deliver high-quality data studies and inform future trials, it is crucial to understand the challenges encountered when managing global multi-centre research studies and to identify solutions that can feasibly be implemented in these settings. This paper provides an overview of the complexities faced by diverse research teams in different countries and regions, together with actions implemented to achieve pragmatic study management of a large multi-centre observational study of neonatal sepsis. We discuss specific considerations for enrolling sites with different approval processes and varied research experience, structures, and training. Implementing a flexible recruitment strategy and providing ongoing training were necessary to overcome these challenges. We emphasize the attention that must be given to designing the database and monitoring plans. Extensive data collection tools, complex databases, tight timelines, and stringent monitoring arrangements can be problematic and might put the study at risk. Finally, we discuss the complexities added when collecting and shipping isolates and the importance of having a robust central management team and interdisciplinary collaborators able to adapt easily and make swift decisions to deliver the study on time and to target. With pragmatic approaches, appropriate training, and good communication, these challenges can be overcome to deliver high-quality data from a complex study in challenging settings through a collaborative research network. Full article

(This article belongs to the Special Issue Tackling Antimicrobial Resistance in Neonatal Infections)

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14 pages, 978 KiB

Open AccessArticle

Clonal Spread of Hospital-Acquired NDM-1-Producing Klebsiella pneumoniae and Escherichia coli in an Italian Neonatal Surgery Unit: A Retrospective Study

by Marilena Agosta, Daniela Bencardino, Marta Argentieri, Laura Pansani, Annamaria Sisto, Marta Luisa Ciofi Degli Atti, Carmen D’Amore, Pietro Bagolan, Barbara Daniela Iacobelli, Mauro Magnani, Massimiliano Raponi, Carlo Federico Perno, Francesca Andreoni and Paola Bernaschi

Antibiotics 2023, 12(4), 642; https://doi.org/10.3390/antibiotics12040642 - 24 Mar 2023

Cited by 2 | Viewed by 1986

Abstract

This article reports a rapid and unexpected spread of colonization cases of NDM-1 carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in a neonatal surgical unit (NSU) at Bambino Gesù Children’s Hospital in Rome, Italy. Between the 16th of November 2020 and the 18th of [...] Read more.

This article reports a rapid and unexpected spread of colonization cases of NDM-1 carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in a neonatal surgical unit (NSU) at Bambino Gesù Children’s Hospital in Rome, Italy. Between the 16th of November 2020 and the 18th of January 2021, a total of 20 NDM-1 carbapenemase-producing K. pneumoniae (n = 8) and E. coli (n = 12) were isolated from 17 out of 230 stool samples collected from neonates admitted in the aforementioned ward and time period by an active surveillance culture program routinely in place to monitor the prevalence of colonization/infection with multidrug-resistant Gram-negative microorganisms. All strains were characterized by antimicrobial susceptibility testing, detection of resistance determinants, PCR-based replicon typing (PBRT) and multilocus-sequence typing (MLST). All isolates were highly resistant to most of the tested antibiotics, and molecular characterization revealed that all of them harbored the bla_NDM-1 gene. Overall, IncA/C was the most common Inc group (n = 20/20), followed by IncFIA (n = 17/20), IncFIIK (n = 14/20) and IncFII (n = 11/20). MLST analysis was performed on all 20 carbapenemase-producing Enterobacterales (CPE) strains, revealing three different Sequence Types (STs) among E. coli isolates, with the prevalence of ST131 (n = 10/12; 83%). Additionally, among the 8 K. pneumoniae strains we found 2 STs with the prevalence of ST37 (n = 7/8; 87.5%). Although patient results were positive for CPE colonization during their hospital stay, infection control interventions prevented their dissemination in the ward and no cases of infection were recorded in the same time period. Full article

(This article belongs to the Special Issue Tackling Antimicrobial Resistance in Neonatal Infections)

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13 pages, 1044 KiB

Open AccessArticle

Evaluating the Use of Neonatal Colonization Screening for Empiric Antibiotic Therapy of Sepsis and Pneumonia

by Alisa Bär, Sabina Schmitt-Grohé, Jürgen Held, Julia Lubig, Gregor Hanslik, Fabian B. Fahlbusch, Heiko Reutter, Joachim Woelfle, Adriana van der Donk, Maria Schleier, Tobias Hepp and Patrick Morhart

Antibiotics 2023, 12(2), 189; https://doi.org/10.3390/antibiotics12020189 - 17 Jan 2023

Cited by 3 | Viewed by 2046

Abstract

(1) Background: Since 2013, weekly screening for multidrug-resistant Gram-negative (MDRGN) bacteria has been performed in German neonatal intensive care units (NICU). National guidelines recommend considering these colonization analyses for antibiotic treatment regimens. Our retrospective single center study provides insight into the clinical dichotomy [...] Read more.

(1) Background: Since 2013, weekly screening for multidrug-resistant Gram-negative (MDRGN) bacteria has been performed in German neonatal intensive care units (NICU). National guidelines recommend considering these colonization analyses for antibiotic treatment regimens. Our retrospective single center study provides insight into the clinical dichotomy of bacterial colonization and infection rates in neonates. (2) Methods: We analyzed microbiological data of neonates admitted to our tertiary level NICU over nine years. Colonization with MDRGN/Serratia marcescens (SERMA) was compared to microbiological findings in sepsis and pneumonia. (3) Results: We analyzed 917 blood and 1799 tracheal aspirate samples. After applying criteria from the Nosocomial Infection Surveillance for Neonates (NEO-KISS), we included 52 and 55 cases of sepsis and pneumonia, respectively; 19.2% of sepsis patients and 34.5% of pneumonia patients had a prior colonization with MDRGN bacteria or SERMA. In these patients, sepsis was not attributable to MDRGN bacteria yet one SERMA, while in pneumonias, ten MDRGN bacteria and one SERMA were identified. We identified late-onset pneumonia and cesarean section as risk factors for MDRGN/SERMA acquisition. (4) Conclusions: Colonization screening is a useful tool for hygiene surveillance. However, our data suggest that consideration of colonization with MDRGN/SERMA might promote extensive use of last resort antibiotics in neonates. Full article

(This article belongs to the Special Issue Tackling Antimicrobial Resistance in Neonatal Infections)

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10 pages, 854 KiB

Open AccessArticle

Epidemiological Analysis of Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae Outbreak in a Neonatal Clinic in Poland

by Agata Pruss, Paweł Kwiatkowski, Helena Masiuk, Iwona Bilska, Stefania Giedrys-Kalemba and Barbara Dołęgowska

Antibiotics 2023, 12(1), 50; https://doi.org/10.3390/antibiotics12010050 - 28 Dec 2022

Cited by 1 | Viewed by 1294

Abstract

Klebsiella pneumoniae is one of the most common etiological agents isolated from epidemic outbreaks in neonatal wards. We describe how an extended-spectrum β-lactamase-producing K. pneumoniae (ESBL-KP) outbreak in a neonatal ward was extinguished. During the outbreak, which lasted over two months, 26 neonates [...] Read more.

Klebsiella pneumoniae is one of the most common etiological agents isolated from epidemic outbreaks in neonatal wards. We describe how an extended-spectrum β-lactamase-producing K. pneumoniae (ESBL-KP) outbreak in a neonatal ward was extinguished. During the outbreak, which lasted over two months, 26 neonates were tested for K. pneumoniae, and 42 environmental swabs were taken. Drug susceptibility was determined for the isolated strains, and their virulence and phylogenetic similarity were checked. ESBL-KP colonization was confirmed in 18 neonates, and six were also confirmed to be infected. All strains isolated from patients represented one clonal type, K. pneumoniae. One strain isolated from an environmental source was determined to be a unique pulsed-field gel electrophoresis pattern. Gestational age and Apgar score were assessed as statistically significant for neonates with ESBL-KP infection. The epidemiological measures taken have been successful, and no further cases appeared. Immediate tightening of hospital hygiene rules, screening of all hospitalized neonates, and cohorting ESBL-KP-positive patients proved effective in controlling and ending the outbreak. The lack of ESBL-KP in the environment suggests that the outbreak was transmitted by colonized hospital staff. This theory could be confirmed by introducing mandatory screening for medical personnel. Full article

(This article belongs to the Special Issue Tackling Antimicrobial Resistance in Neonatal Infections)

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12 pages, 502 KiB

Open AccessArticle

Successful Control of an Outbreak by Phenotypically Identified Extended-Spectrum Beta-Lactamase–Producing Klebsiella pneumoniae in a Neonatal Intensive Care Unit

by Elena Priante, Chiara Minotti, Cristina Contessa, Margherita Boschetto, Paola Stano, Federico Dal Bello, Ettore De Canale, Elisabetta Lolli, Vincenzo Baldo, Eugenio Baraldi and Daniele Donà

Antibiotics 2022, 11(11), 1649; https://doi.org/10.3390/antibiotics11111649 - 18 Nov 2022

Cited by 2 | Viewed by 1850

Abstract

Background: Premature newborns represent a vulnerable population, at high risk of acquiring nosocomial infections during neonatal intensive care unit (NICU) admission. Multidrug-resistant organisms represent the greatest concern due to their intrinsic virulence and the limited therapeutic options. Resistant Enterobacterales are a growing threat [...] Read more.

Background: Premature newborns represent a vulnerable population, at high risk of acquiring nosocomial infections during neonatal intensive care unit (NICU) admission. Multidrug-resistant organisms represent the greatest concern due to their intrinsic virulence and the limited therapeutic options. Resistant Enterobacterales are a growing threat for critically ill neonates, with increasing numbers of NICU outbreaks caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales being described. This study reports the early detection and successful control of an outbreak caused by ESBL-producing Klebsiella pneumoniae (ESBL-KP) in an Italian NICU in February 2021. Results: A total of 13 newborns tested positive for ESBL-KP between 2–9 February 2021, of whom four (31%) had a bloodstream infection. Two were critically ill, extremely premature newborns who died because of multiple comorbidities, and two were cured after treatment with meropenem. All other patients survived and were either discharged home or moved to other hospitals/wards in good clinical condition. ESBL-KP ST45 was found in all isolates by multilocus sequence typing (MLST) analysis. An outbreak control plan was set, including surveillance cultures for all neonates, NICU environments, and medical devices, along with the extended use of contact precautions and cohorting. In addition, the infection control plan was carried out through reinforcement and enhancement measures to guarantee maximal compliance. The outbreak was successfully controlled in seven days, given that no further cases were identified after 9 February. The source of the ESBL-KP outbreak was not identified through environmental sampling. Conclusions: Thanks to multidisciplinary management, a threatening outbreak of ESBL-KP in a NICU was controlled in few days. The prompt recognition of the event onset and the adoption of infection control interventions helped contain the bacteria spread on the ward. Full article

(This article belongs to the Special Issue Tackling Antimicrobial Resistance in Neonatal Infections)

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10 pages, 272 KiB

Open AccessArticle

Neonatal Early Onset Sepsis (EOS) Calculator plus Universal Serial Physical Examination (SPE): A Prospective Two-Step Implementation of a Neonatal EOS Prevention Protocol for Reduction of Sepsis Workup and Antibiotic Treatment

by Francesco Cavigioli, Francesca Viaroli, Irene Daniele, Michela Paroli, Luigi Guglielmetti, Elena Esposito, Francesco Cerritelli, Gianvincenzo Zuccotti and Gianluca Lista

Antibiotics 2022, 11(8), 1089; https://doi.org/10.3390/antibiotics11081089 - 11 Aug 2022

Cited by 3 | Viewed by 1955

Abstract

Current neonatal early-onset sepsis (EOS) guidelines lack consensus. Recent studies suggest three different options for EOS risk assessment among infants born ≥35 wks gestational age (GA), leading to different behaviors in the sepsis workup and antibiotic administration. A broad disparity in clinical practice [...] Read more.

Current neonatal early-onset sepsis (EOS) guidelines lack consensus. Recent studies suggest three different options for EOS risk assessment among infants born ≥35 wks gestational age (GA), leading to different behaviors in the sepsis workup and antibiotic administration. A broad disparity in clinical practice is found in Neonatal Units, with a large number of non-infected newborns evaluated and treated for EOS. Broad spectrum antibiotics in early life may induce different short- and long-term adverse effects, longer hospitalization, and early mother-child separation. In this single-center prospective study, a total of 3002 neonates born in three periods between 2016 and 2020 were studied, and three different workup algorithms were compared: the first one was based on the categorical risk assessment; the second one was based on a Serial Physical Examination (SPE) strategy for infants with EOS risk factors; the third one associated an informatic tool (Neonatal EOS calculator) with a universal extension of the SPE strategy. The main objective of this study was to reduce the number of neonatal sepsis workups and the rate of antibiotic administration and favor rooming-in and mother–infant bonding without increasing the risk of sepsis and mortality. The combined strategy of universal SPE with the EOS Calculator showed a significant reduction of laboratory tests (from 33% to 6.6%; p < 0.01) and antibiotic treatments (from 8.5% to 1.4%; p < 0.01) in term and near-term newborns. EOS and mortality did not change significantly during the study period. Full article

(This article belongs to the Special Issue Tackling Antimicrobial Resistance in Neonatal Infections)

Review

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15 pages, 343 KiB

Open AccessReview

Fighting Antimicrobial Resistance in Neonatal Intensive Care Units: Rational Use of Antibiotics in Neonatal Sepsis

by Dimitrios Rallis, Vasileios Giapros, Anastasios Serbis, Chrysoula Kosmeri and Maria Baltogianni

Antibiotics 2023, 12(3), 508; https://doi.org/10.3390/antibiotics12030508 - 03 Mar 2023

Cited by 4 | Viewed by 3294

Abstract

Antibiotics are the most frequently prescribed drugs in neonatal intensive care units (NICUs) due to the severity of complications accompanying neonatal sepsis. However, antimicrobial drugs are often used inappropriately due to the difficulties in diagnosing sepsis in the neonatal population. The reckless use [...] Read more.

Antibiotics are the most frequently prescribed drugs in neonatal intensive care units (NICUs) due to the severity of complications accompanying neonatal sepsis. However, antimicrobial drugs are often used inappropriately due to the difficulties in diagnosing sepsis in the neonatal population. The reckless use of antibiotics leads to the development of resistant strains, rendering multidrug-resistant pathogens a serious problem in NICUs and a global threat to public health. The aim of this narrative review is to provide a brief overview of neonatal sepsis and an update on the data regarding indications for antimicrobial therapy initiation, current guidance in the empirical antimicrobial selection and duration of therapy, and indications for early discontinuation. Full article

(This article belongs to the Special Issue Tackling Antimicrobial Resistance in Neonatal Infections)

13 pages, 807 KiB

Open AccessReview

Group B Streptococcus Early-Onset Disease: New Preventive and Diagnostic Tools to Decrease the Burden of Antibiotic Use

by Charlotte M. Nusman, Linde Snoek, Lisanne M. van Leeuwen, Thomas H. Dierikx, Bo M. van der Weijden, Niek B. Achten, Merijn W. Bijlsma, Douwe H. Visser, Marlies A. van Houten, Vincent Bekker, Tim G. J. de Meij, Ellen van Rossem, Mariet Felderhof and Frans B. Plötz

Antibiotics 2023, 12(3), 489; https://doi.org/10.3390/antibiotics12030489 - 01 Mar 2023

Cited by 2 | Viewed by 1882

Abstract

The difficulty in recognizing early-onset neonatal sepsis (EONS) in a timely manner due to non-specific symptoms and the limitations of diagnostic tests, combined with the risk of serious consequences if EONS is not treated in a timely manner, has resulted in a low [...] Read more.

The difficulty in recognizing early-onset neonatal sepsis (EONS) in a timely manner due to non-specific symptoms and the limitations of diagnostic tests, combined with the risk of serious consequences if EONS is not treated in a timely manner, has resulted in a low threshold for starting empirical antibiotic treatment. New guideline strategies, such as the neonatal sepsis calculator, have been proven to reduce the antibiotic burden related to EONS, but lack sensitivity for detecting EONS. In this review, the potential of novel, targeted preventive and diagnostic methods for EONS is discussed from three different perspectives: maternal, umbilical cord and newborn perspectives. Promising strategies from the maternal perspective include Group B Streptococcus (GBS) prevention, exploring the virulence factors of GBS, maternal immunization and antepartum biomarkers. The diagnostic methods obtained from the umbilical cord are preliminary but promising. Finally, promising fields from the newborn perspective include biomarkers, new microbiological techniques and clinical prediction and monitoring strategies. Consensus on the definition of EONS and the standardization of research on novel diagnostic biomarkers are crucial for future implementation and to reduce current antibiotic overexposure in newborns. Full article

(This article belongs to the Special Issue Tackling Antimicrobial Resistance in Neonatal Infections)

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13 pages, 1010 KiB

Open AccessReview

Effects of Perinatal Antibiotic Exposure and Neonatal Gut Microbiota

by Chiara Morreale, Cristina Giaroni, Andreina Baj, Laura Folgori, Lucia Barcellini, Amraj Dhami, Massimo Agosti and Ilia Bresesti

Antibiotics 2023, 12(2), 258; https://doi.org/10.3390/antibiotics12020258 - 28 Jan 2023

Cited by 9 | Viewed by 2518

Abstract

Antibiotic therapy is one of the most important strategies to treat bacterial infections. The overuse of antibiotics, especially in the perinatal period, is associated with long-lasting negative consequences such as the spread of antibiotic resistance and alterations in the composition and function of [...] Read more.

Antibiotic therapy is one of the most important strategies to treat bacterial infections. The overuse of antibiotics, especially in the perinatal period, is associated with long-lasting negative consequences such as the spread of antibiotic resistance and alterations in the composition and function of the gut microbiota, both of which negatively affect human health. In this review, we summarize recent evidence about the influence of antibiotic treatment on the neonatal gut microbiota and the subsequent negative effects on the health of the infant. We also analyze the possible microbiome-based approaches for the re-establishment of healthy microbiota in neonates. Full article

(This article belongs to the Special Issue Tackling Antimicrobial Resistance in Neonatal Infections)

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14 pages, 3481 KiB

Open AccessReview

Staphylococcal Scalded Skin Syndrome in Neonates: Case Series and Overview of Outbreaks

by Charlotte M. Nusman, Charlotte Blokhuis, Dasja Pajkrt and Douwe H. Visser

Antibiotics 2023, 12(1), 38; https://doi.org/10.3390/antibiotics12010038 - 26 Dec 2022

Cited by 5 | Viewed by 5188

Abstract

Skin and soft tissue infections caused by Staphylococcus aureus (S. aureus) cover a wide spectrum of diseases in neonates, including staphylococcal scalded skin syndrome (SSSS). We describe a representative case of SSSS in neonatal twins, which despite recurrence showed a mild [...] Read more.

Skin and soft tissue infections caused by Staphylococcus aureus (S. aureus) cover a wide spectrum of diseases in neonates, including staphylococcal scalded skin syndrome (SSSS). We describe a representative case of SSSS in neonatal twins, which despite recurrence showed a mild clinical disease course. This case was part of a small outbreak on a neonatal intensive care unit and therefore exemplifies the existence of neonatal outbreaks with skin and soft tissue infections by S. aureus. Diagnosis is generally based on the clinical picture and response to antibiotics, but can be aided by histology and cultures. Sequence-based molecular techniques are available to evaluate typing and virulence of S. aureus in outbreak or surveillance settings. The pillars of treatment are antibiotics and supportive care. Methicillin resistance remains a topic of concern, especially in outbreak settings. Our overview of numerous outbreaks of neonatal S. aureus skin infections underlines the importance of outbreak management strategies, including screening to identify the source of the outbreak, and limiting exposure through hygienic measures and establishment of physical boundaries. Full article

(This article belongs to the Special Issue Tackling Antimicrobial Resistance in Neonatal Infections)

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Other

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15 pages, 833 KiB

Open AccessSystematic Review

Therapeutic Options and Outcomes for the Treatment of Neonates and Preterms with Gram-Negative Multidrug-Resistant Bacteria: A Systematic Review

by Lorenzo Chiusaroli, Cecilia Liberati, Maria Caseti, Luigi Rulli, Elisa Barbieri, Carlo Giaquinto and Daniele Donà

Antibiotics 2022, 11(8), 1088; https://doi.org/10.3390/antibiotics11081088 - 10 Aug 2022

Cited by 4 | Viewed by 2512

Abstract

(1) Background: Infections caused by multidrug-resistant (MDR) or extensively drug-resistant (XDR) bacteria represent a challenge in the neonatal population due to disease severity and limited therapeutic possibilities compared to adults. The spread of antimicrobial resistance and drug availability differ significantly worldwide. The incidence [...] Read more.

(1) Background: Infections caused by multidrug-resistant (MDR) or extensively drug-resistant (XDR) bacteria represent a challenge in the neonatal population due to disease severity and limited therapeutic possibilities compared to adults. The spread of antimicrobial resistance and drug availability differ significantly worldwide. The incidence of MDR bacteria has constantly risen, causing an increase in morbidity, mortality, and healthcare costs in both high-income (HIC) and low- and middle-income countries (LMIC). Therefore, more evidence is needed to define the possible use of newer molecules and to optimize combination regimens for the oldest antimicrobials in neonates. This systematic review aims to identify and critically appraise the current antimicrobial treatment options and the relative outcomes for MDR and XDR Gram-negative bacterial infections in the neonatal population. (2) Methods: A literature search for the treatment of MDR Gram-negative bacterial infections in neonates (term and preterm) was conducted in Embase, MEDLINE, and Cochrane Library. Studies reporting data on single-patient-level outcomes related to a specific antibiotic treatment for MDR Gram-negative bacterial infection in children were included. Studies reporting data from adults and children were included if single-neonate-level information could be identified. We focused our research on four MDROs: Enterobacterales producing extended-spectrum beta-lactamase (ESBL) or carbapenemase (CRE), Pseudomonas aeruginosa, and Acinetobacter baumannii. PROSPERO registration: CRD42022346739 (3) Results: The search identified 11,740 studies (since January 2000), of which 22 fulfilled both the inclusion and exclusion criteria and were included in the analysis. Twenty of these studies were conducted in LMIC. Colistin is the main studied and used molecule to treat Gram-negative MDR bacteria for neonate patients in the last two decades, especially in LMIC, with variable evidence of efficacy. Carbapenems are still the leading antibiotics for ESBL Enterobacterales, while newer molecules (i.e., beta-lactam agents/beta-lactamase inhibitor combination) are promising across all analyzed categories, but data are few and limited to HICs. (4) Conclusions: Data about the treatment of Gram-negative MDR bacteria in the neonatal population are heterogeneous and limited mainly to older antimicrobials. Newer drugs are promising but not affordable yet for many LMICs. Therefore, strategies cannot be generalized but will differ according to the country’s epidemiology and resources. More extensive studies are needed to include new antimicrobials and optimize the combination strategies for the older ones. Full article

(This article belongs to the Special Issue Tackling Antimicrobial Resistance in Neonatal Infections)

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