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Emergence of invasive Streptococcus dysgalactiae subsp. equisimilis in Spain (2012-2022): genomic insights and clinical correlations
Authors: Guillem López de Egea
Abstract
Objectives: An increase in Streptococcus dysgalactiae subsp. equisimilis (SDSE) infections has been documented worldwide. This study aims to analyze invasive disease caused by SDSE (iSDSE) in adults over an 11-year period in Spain.
Methods: We conducted a retrospective, laboratory-based study of iSDSE detected at Hospital Universitari de Bellvitge (HUB) from 2012 to 2022 (n = 89) and isolates collected in three Spanish hospitals in 2018 (n = 22). Clinical data from HUB were collected. Isolates were tested for antimicrobial susceptibility (European Committee on Antimicrobial Susceptibility Testing 2023), subjected to whole genome sequencing and analyzed for mobile genetic elements (MGEs). A mouse model was used to analyze virulence.
Results: iSDSE episodes at HUB occurred predominantly in older patients with comorbidities (particularly, diabetes, chronic heart disease, and malignancies). Whole genome sequencing revealed a high genetic diversity, with the most common lineages being CC15, CC17, and CC20. Various virulence factors, including the superantigen speG, were identified. Macrolides, lincosamides, and tetracyclines exhibited the highest resistance rates (>27%) and changed over time, linked to multiple MGEs. The mouse model highlighted the virulence of the CC20-stG62647 lineage, but these results were discordant with clinical data.
Conclusion: iSDSE incidence is increasing and associated with older patients with comorbidities. Genetically, SDSE is diverse with a high capacity to integrate MGEs carrying resistance determinants. Mouse model studies showed the enhanced virulence of the CC20-stG62647 lineage. These findings underscore the need for ongoing surveillance of this emerging pathogen.
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Acute respiratory tract infections during the first 6 years of life – results from the German birth cohort study LoewenKIDS
Authors: Bianca Klee
Abstract
Objectives: Acute respiratory tract infections (ARIs) often occur in early childhood and are mostly selflimited. However, they impose a high socioeconomic burden and can be associated with chronic diseases later in life. To date, data on self-reported ARIs beyond infancy are limited. This study aimed to describe the incidence and characteristics of self-reported ARIs in the first 6 years of life.
Methods: Data were obtained from the LoewenKIDS birth cohort study, including 782 children born between 2014 and 2018. Parents recorded daily ARI symptoms, which were classified into episodes for incidence and characteristics analysis. Regression analyses explored the influence of exposure factors on ARI incidence.
Results: This longitudinal birth cohort study of a subsample of 258 children found a mean cumulative duration of 51.5 weeks (95% confidence interval: 47.5-55.6 weeks) of respiratory symptoms in the first 6 years of life, with large individual differences. Children with frequent infections in infancy had more infections in preschool age. Exposure factors explained only a small fraction of variation in incidence (5%).
Conclusions: There is a substantial variation in susceptibility to ARIs in childhood, which is not explained by exposure factors.
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Fungal biomarkers in HIV-associated disseminated histoplasmosis: a multicenter diagnostic accuracy study on the Guiana shield
Authors: Aurore Moussiegt
Highlights
• Histoplasmosis is the first opportunistic infection in patients living with HIV in South America.
• Its diagnosis remains challenging.
• Fungal markers have scarcely been studied in HIV-associated histoplasmosis.
• (1→3)-β-D-Glucan is very sensitive but lacks specificity for this diagnosis.
• Galactomannan is sensitive and specific, with an optimal threshold of 1.29.
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Revolutionizing clinical laboratories: The impact of artificial intelligence in diagnostics and patient care
Authors: Asem Ali Asraf
Highlights
• AI improves the efficiency and accuracy of diagnostics in microbiology and pathology.
• In clinical laboratories, automated operations increase reproducibility and decrease errors.
• Personalised patient treatment and early detection are made possible by AI-driven biomarker analysis.
• Responsible AI integration in healthcare requires ethical and legal frameworks.
• A revolutionary future for diagnostic labs is being heralded by the merging of robotics and IoT.
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A real-world investigation into prescribing patterns and effectiveness of ceftolozane/tazobactam among critically ill patients from SPECTRA
Authors: Alex Soriano
Highlights
• This is a real-world study of ceftolozane/tazobactam in critical care patients.
• Clinical success was higher when ceftolozane/tazobactam was used as first line.
• Comorbidities, respiratory infections, and resistant organisms were common.
• Most patients had beneficial outcomes despite their clinical complexity.
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Impact of Antimicrobial Stewardship and Infection Prevention and Control Programmes on Antibiotic Usage and A. baumannii resistance: A 2016-2023 Multicentre Prospective Study.
DOI: 10.2147/idr.s505133
Authors: Liu L et al
Abstract
Objective: This study assesses the efficacy of antimicrobial stewardship (AMS) and infection prevention and control programmes (IPCP) in guiding the use of antibiotics and the control of A. baumannii (AB) resistance at multiple medical centres.
Methods: The effectiveness of the policy on antibiotic consumption and AB resistance by determining the relationship between the defined daily doses (DDD) for antibiotics – or alcohol-based hand gel (ABHG) consumption – and the incidence of carbapenem-resistant AB (CR-AB), multidrug-resistant AB (MDR-AB) and extensively drug-resistant AB (XDR-AB) was evaluated at two medical centers from 2016-2023.
Results: In total, 4057 AB isolates were collected; 64.95% of the AB isolates were CR, 59.48% were MDR and 1.41% were XDR. The major categories of the AB clinical strains collected were extracted primarily from patients’ respiratory tract specimens, the ICU wards and patients over 65 years old, accounting for 76.98%, 67.98% and 63.72%, respectively. The incidence of CR-AB, MDR-AB and XDR-AB based on AMS and IPCP measures ranged from 70.04% to 58.42% (P<0.0001), 64.26% to 52.16% (P<0.0001) and 2.27% to 0.60% (P=0.0167), respectively. The DDD of total antibiotics administered per 1000 patient days (PD) decreased significantly from 51.25±4.22 to 40.92±2.48 (P<0.0001), and ABHG consumption per 1000 PD increased significantly from 5.25±0.98 to 13.51±5.12 (P<0.0001). We found a statistically significant positive correlation between the DDD of antibiotic consumption and the incidence of CR-AB, MDR-AB and XDR-AB (r=0.9755 and P<0.0001, r=0.9571 and P=0.0002, r=0.9230 and p=0.0011, respectively). In addition, a statistically negative correlation was found between ABHG consumption and the incidence of CR-AB, MDR-AB, and XDR-AB (r=-0.9473 and P=0.0004, r=-0.9123 and P=0.0016, r=-0.9138 and P=0.0015, respectively).
Conclusion: Comprehensive AMS and IPCP intervention measures can successfully achieve a sustained amelioration in the resistance and transmission of CR-AB, MDR-AB and XDR-AB, which are regarding potential applicability to other hospitals.
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Infection Risk in Patients with Mixed Flora in Urine Cultures Prior to Ureteroscopy.
Authors: Joshua K Kim et al
Abstract
Purpose: Urine cultures are routinely used to inform preoperative antibiotic choice and duration prior to endourologic surgery. The presence of mixed flora in preoperative urine cultures holds unclear clinical significance. This study examines infectious outcomes after ureteroscopy in patients with preoperative mixed flora urine cultures.
Materials and Methods: A retrospective cohort study was conducted on adult patients who underwent ureteroscopy with laser lithotripsy between January 2014 and June 2024 who had urine cultures performed within 60 days preoperatively. Patients were categorized into cohorts based on their preoperative urine culture: mixed flora, negative, or positive. Postoperative urinary tract infection rates within 30 days were compared between cohorts, and logistic regression was performed adjusting for demographic and clinical variables.
Results: 5166 patients who underwent ureteroscopy with laser lithotripsy (2139 mixed flora, 1525 negative, 1502 positive) were identified. Preoperative antibiotics were used more often in the mixed flora cohort (29%) than in the negative cohort (24%, p = 0.007) but less frequently than in the positive cohort (57%, p < 0.001). Postoperative infections were visualized in 165 patients (8%) in the mixed flora cohort, compared with 88 (6%) in the negative cohort (p = 0.067) and 237 (16%) in the positive cohort (p < 0.001). Multivariable logistic regression demonstrated that positive cultures were associated with an increased risk of infection (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.49-2.55, p < 0.001), but negative cultures had a similar risk of infection compared with mixed flora (OR = 0.79, 95% CI = 0.56-1.11, p = 0.177). Within the mixed flora cohort, preoperative antibiotic treatment was not associated with decreased postoperative infection (OR = 0.99, 95% CI = 0.66-1.47, p = 0.964).
Conclusions: While patients with preoperative mixed flora urine cultures received preoperative antibiotics more often than patients with negative urine cultures, they were not at higher risk for postoperative infection. Routine preoperative antibiotic use in patients with mixed flora cultures may not be effective in reducing infectious complications after ureteroscopy.
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Association of Doses Based on Body Constitutional Parameters with the Efficacy of Micafungin in Candidemia.
DOI: 10.2147/idr.s505133
Authors: Masaya Nagamizu et al
Abstract
Background: Invasive candidiasis is a life-threatening infection associated with high mortality, necessitating early and effective treatment. Micafungin, an echinocandin, is recommended as initial therapy for invasive candidiasis. However, the optimal micafungin dose relative to patients’ body constitutional parameters (BCPs) remains unclear. This study aimed to evaluate the relationship between the dose of micafungin per BCPs (Dose/BCPs) and treatment outcomes.
Methods: This two-center retrospective study included patients treated with micafungin who had confirmed positive blood cultures for Candida species between January 1, 2010, and December 31, 2020. The association between Dose/BCP and treatment success, as well as time to recovery following micafungin therapy was assessed.
Results: Eighty-three patients were included in the analysis, with a median age of 78 years. The primary isolated Candida species were Candida albicans (n = 34), Candida parapsilosis (n = 19), and Candida glabrata (n = 16). The treatment success rate was 44.6% and was significantly associated with age ≥ 75 years. Although no significant differences in Dose/BCP were observed between the success and failure groups, patients with a Dose/BSA ≥ 100 mg/m2 experienced a significantly shorter time to recovery with micafungin therapy.
Conclusion: This study identified an association between Dose/BSA and the time to recovery with micafungin therapy. While some missing data, including APACHE-II scores, limit the robustness of the findings because of the retrospective design, dose adjustment to achieve Dose/BSA ≥ 100 mg/m2 may be beneficial in antifungal stewardship. This adjustment could reduce treatment duration with this broad-spectrum antifungal agent.
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Observational study of antibiotic prescribing patterns by age and sex in primary care in England: why we need to take this variation into account to evaluate antibiotic stewardship and predict AMR variation.
Authors: Naomi R Waterlow et al
Abstract
Background: The drivers of antimicrobial resistance (AMR) likely vary substantially by different demographics. However, few complete, open, national detailed data exist on how antibiotic use (ABU) varies by both age and sex. Here, the authors aimed to describe the variation in ABU and consider how these age- and sex-specific patterns influence targets and methods for AMR control.
Methods: Prescriptions of all antibiotics from general practices in England for 2015-23 disaggregated by 5 year age bands and sex were analysed at the national and Integrated Care Board (ICB) level. A descriptive analysis of the relative rates of ABU by age and sex was conducted, followed by an evaluation of comparison metrics of prescription levels between regions. ABU by age and sex were compared with global AWaRe targets, and ABU by age-group was correlated against influenza vaccination introduction, to evaluate the impact of such vaccines on ABU.
Results: From a total of 249 578 795 prescriptions (across 9 years), 63% were given to women and the most prescribed were amoxicillin, nitrofurantoin and flucloxacillin sodium. Prescriptions per 100 000 population varied substantially across sex, age, geographical region, season, year, COVID-19 pandemic period and drug. Most antibiotics were prescribed more to women across most age bands (84% of antibiotics had more prescriptions to females across 50% of age bands). This variation requires a more nuanced approach to comparing ABU across geographies and highlight that AWaRe targets are not met uniformly [prescribing in men aged 11-20 does not fulfil the Access, Watch and Reserve (AWaRe) 80% Access target]. The study also show the impact on ABU of time-sensitive interruptions (38% of antibiotics showed a seasonal pattern in the absence of disruptions), including differential age-targeted influenza vaccination, COVID-19 restrictions and a shortage of amoxicillin due to a group A Streptococcus outbreak.
Conclusions: These detailed differences in ABU across England suggest that there should be large variation in AMR burden by age and sex. Linkage of this ABU data with similarly detailed open-access AMR data is now needed for better intervention design.
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Effect of biannual azithromycin on respiratory pathogens among symptomatic children: results from the randomised Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) I trial
Authors: Liu J
Abstract
Introduction: Biannual (ie, every 6 months) mass drug administration of azithromycin has reduced childhood mortality in Niger, but its effects on specific respiratory pathogens are not fully elucidated.
Methods: Across 2 years of the Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) study in Niger, we evaluated 1468 nasopharyngeal swabs from children who presented for care with respiratory symptoms. Swabs were tested by quantitative PCR using a customised TaqMan Array Card that included assays for 19 respiratory pathogens.
Results: Nasopharyngeal detection of Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae was common in both azithromycin and placebo communities. The prevalence was reduced in children from azithromycin communities for just two pathogens: Bordetella pertussis and H. influenzae type b (Hib). These children had a 49% and 65% reduction in the prevalence of B. pertussis and Hib in nasopharyngeal swabs, respectively, compared with children from the control communities (prevalence ratios 0.51, 95% CI 0.35, 0.75; and 0.35, 95% CI 0.17, 0.71).
Conclusions: Biannual administration of azithromycin to communities in Niger was associated with lower prevalence of B. pertussis and Hib compared with placebo. These reductions may explain some of the childhood mortality benefit of azithromycin.
Trial registration number: NCT02048007.
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Is Tailored Bismuth Quadruple Therapies (With Clarithromycin or Furazolidone) Based on Fecal Molecular Susceptibility Testing in First-Line Helicobacter pylori Eradication Treatment More Effective? A Three-Arm, Multicenter Randomized Clinical Trial
DOI: 10.1111/hel.70018
Authors: Zhengchen Yu
Abstract
Background: Rising antimicrobial resistance has significantly challenged the eradication rates of Helicobacter pylori. Due to its invasive nature, susceptibility testing based on endoscopic biopsy is controversial, while few studies have focused on the efficacy of tailored bismuth quadruple therapies (BQT) based on fecal susceptibility testing as a first-line treatment.
Methods: In this multicenter study, 598 H. pylori-positive patients without previous eradication treatment were recruited and randomly assigned to three groups: empirical BQT, BQT-tailored based on the history of clarithromycin use and tailored based on fecal molecular susceptibility testing where furazolidone was substituted for clarithromycin when there was clinical or laboratory evidence of clarithromycin resistance. This study defines BQT as regimens comprising rabeprazole, colloidal bismuth, amoxicillin, and one additional antibiotic (furazolidone or clarithromycin). The study assessed eradication rates using intention-to-treat (ITT), modified intention-to-treat (mITT), and per-protocol (PP) analyses.
Results: The eradication rates of three groups were 82.00%, 80.90%, and 87.44% in the ITT analysis; 82.41%, 83.42%, and 89.23% in the mITT analysis; and 85.86%, 87.50%, and 94.57% in the PP analysis, respectively. Tailored BQT based on fecal susceptibility testing was not inferior to empirical BQT (all p values for noninferiority < 0.001) and demonstrated greater efficacy in the PP analysis (difference [95% CI]: 7.07% [0.90%, 13.25%]). The incidence of adverse events and treatment compliance did not differ significantly among the groups.
Conclusion: Tailored BQT based on fecal susceptibility testing is an effective regimen for H. pylori eradication, with no increase in adverse events or treatment noncompliance compared with empirical BQT. Therefore, we recommend tailored BQT based on fecal susceptibility testing as a first-line treatment.
Trial registration: EudraCT number: NCT05718609; ClinicalTrials.gov.
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Phase I Study of the Safety, Tolerability, and Pharmacokinetics of Inhaled Voriconazole in Healthy Volunteers and Subjects With Stable Asthma
DOI: 10.1002/prp2.70064
Authors: Giovanni Caponetti
Abstract
The aim of this study was to evaluate safety, tolerability, and pharmacokinetics (PK) of single and multiple doses of a novel inhaled formulation of voriconazole (ZP-059). In the single ascending dose part, 4 cohorts of 6 healthy subjects received one dose of inhaled voriconazole (5-40 mg). In the multiple ascending dose part, 3 cohorts of 6 subjects with mild asthma received voriconazole 10 mg twice daily [BID], 20 mg BID or 40 mg once daily. In the 2-period crossover part, 16 subjects with mild to moderate asthma each received one dose of inhaled voriconazole 20 mg and one dose of oral voriconazole 200 mg. A bioanalytical method was developed and validated to simultaneously determine concentrations of voriconazole and its metabolite N-oxide voriconazole in serum and sputum. Inhaled voriconazole was well tolerated with no treatment emergent adverse events (TEAEs) leading to treatment discontinuation. The PK profile of inhaled voriconazole showed rapid absorption, apparent greater than proportional increase in exposure with increasing dose, a consistent half-life across dosing, and large clearance and volume of distribution. Following repeat administration limited accumulation was observed. Systemic exposure following inhaled voriconazole was much lower than following oral voriconazole. Serum data confirmed that voriconazole was extensively metabolized also when administered by inhalation. Sputum data following inhaled voriconazole were limited but demonstrated increasing exposure with increasing dose. The current study shows the newly developed dry powder inhaled formulation of voriconazole to be safe and well tolerated, providing a possible improved treatment approach for patients affected by allergic bronchopulmonary aspergillosis. Trial Registration: ClinicalTrials.gov ID: NCT04229303.
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Peer-assisted telemedicine hepatitis-C treatment for people who use drugs in rural communities: a mixed methods study
Authors: Kim Hoffman
Abstract
Background: The increase in opioid use disorder among young, nonurban people has fueled sharp rises in hepatitis C virus (HCV) infections. Innovative treatment models are needed that circumvent healthcare system barriers for people who use drugs (PWUD), particularly in rural areas. The Oregon HOPE TeleHCV study randomized PWUD living with HCV in rural Oregon to peer-facilitated and streamlined telemedicine HCV treatment (Peer TeleHCV) versus enhanced usual care (EUC) and assessed sustained virologic response at 12 weeks post treatment (SVR12). Peer Support Specialists (peers) conducted HCV screening in the community, facilitated pretreatment evaluation and linkage to telemedicine HCV treatment clinicians, and supported Peer TeleHCV study participants in HCV medication adherence. A qualitative investigation queried telemedicine clinicians and peers about their experiences with the implementation of the model and key drivers of implementation effectiveness.
Methods: Two remote audio/video recorded focus groups were conducted, one with the study’s clinicians and one with the peers. Participants were asked their views of key elements for successful implementation and outcomes of the Peer TeleHCV model. Group interviews lasted one hour. Recordings were professionally transcribed for thematic analysis with a mixed deductive and inductive framework, using Atlas.ti. Patients were surveyed about their interactions and satisfaction with peers.
Results: Quantitative data (n = 78) indicated patients had high levels of satisfaction with and support from the peers. Three themes were identified from the qualitative data (n = 12) including. (1) Key peer-level elements such as providing support during potentially difficult lab draws, creating a peer-facilitated “bubble of trust” between patients and clinicians, enabling technology access, conducting outreach to maintain contact and support treatment retention, and facilitating stabilizing wrap-around services (e.g., housing vouchers) (2) Key clinician-level factors such as capacity for unscheduled peer-facilitated appointments, having dedicated time for case consults with peers, and clinicians trained in working with PWUD and skilled in identifying related clinical concerns (3) Key systems-level elements such as standing lab orders, challenges related to specialty pharmacies and Medicaid managed care organizations, and streamlined communication strategies between peers and clinicians.
Conclusion: All participants reported that the Peer TeleHCV model built trust and eased barriers for PWUD initiating and remaining in HCV treatment. This low-barrier model makes space for PWUD to receive HCV treatment, regardless of drug use. Implementing support from peer specialists, telemedicine technology, and streamlined testing and treatment strategies may connect more rural PWUD living with HCV with the cure.
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Efficacy of dolutegravir plus lamivudine in treatment-naive people living with HIV without baseline drug-resistance testing available (D2ARLING): 48-week results of a phase 4, randomised, open-label, non-inferiority trial
Authors: Ezequiel Cordova
Abstract
Background: Dolutegravir plus lamivudine has emerged as a preferred treatment for HIV; however, initiating this regimen without baseline resistance testing raises concerns about the potential presence of pretreatment lamivudine resistance. We aimed to evaluate the efficacy of dolutegravir plus lamivudine in the absence of information on baseline resistance testing in treatment-naive people with HIV.
Methods: We did an open-label, non-inferiority, single-centre, phase 4, randomised controlled study (D2ARLING), designed to assess the efficacy and safety of dolutegravir plus lamivudine in treatment-naive people with HIV with no available baseline resistance testing. We included participants aged 18 years or older with HIV-1 diagnosis who were naive to antiretroviral therapy and had no baseline genotypic resistance testing result available. We randomly assigned (1:1) participants to receive dolutegravir 50 mg plus lamivudine 300 mg or a three-drug regimen including dolutegravir 50 mg plus tenofovir disoproxil fumarate 300 mg and either emtricitabine 200 mg or lamivudine 300 mg. Randomisation was stratified by baseline HIV-1 RNA (≤100 000 vs >100 000 copies per mL) and CD4 cell count (<200 vs ≥200 cells per μL). Per protocol, we performed genotypic drug-resistance testing on day 1 and it remained double-masked throughout the study, simulating a scenario of inaccessibility of baseline resistance testing. The primary endpoint was the proportion of participants with plasma HIV-1 RNA less than 50 copies per mL at week 48 (intention-to-treat exposed analysis via the Snapshot algorithm) with prespecified non-inferiority margin of 10%. This trial is registered with ClinicalTrials.gov (NCT04549467).
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Prevention of VAP Using Hypertonic Saline Nebulization in NICU: A Randomized Controlled Trial
Authors: Arpit Gupta
Abstract
Objective: To evaluate the efficacy and safety of hypertonic saline (HS) nebulization in reducing the occurrence of ventilator associated pneumonia (VAP) by comparison of modified Clinical Pulmonary Infection Score (mCPIS) in HS nebulized and non-nebulized newborns.
Methods: A randomized controlled study with 1:1 participant allocation ratio was conducted in a tertiary centre in North India. Neonates who received mechanical ventilation at the centre were included. Those who had been intubated for >12 hours at outside hospitals were excluded. The study group received nebulization with HS for seven days or till extubation (whichever was earlier). Both groups were compared in terms of occurrence of VAP and mCPIS. mCPIS ≥ 6 was used to suggest VAP. VAP was confirmed by a positive blood culture in ventilated newborns with clinicoinvestigative features of VAP.
Results: A total of 143 neonates were analyzed in each group. VAP rate (per 1000 mechanical ventilation-days) in the HS nebulization and the control groups were 36.72 and 51.51, respectively; P = 0.031. A 33.52% reduction in the rate of VAP was observed due to HS nebulization. [RR (95% CI) 0.67 (0.47, 0.95), P = 0.022]. The mean (SD) mCPIS in HS group was 5.22 (0.88) compared to 5.94 (1.07) in the control group; P = 0.030. Only 5.5% neonates in the intervention group developed wheezing.
Conclusion: Nebulization with HS reduces the incidence of VAP in ventilated newborns without significant side effects.