Successful Whole Genome Sequencing-guided Treatment of Mycoplasma hominis Ventriculitis in a Preterm Infant

Huang, Felicia A Scaggs; Mortensen, Joel E.; Skoch, Jesse; Andersen, Heidi; Staat, Mary Allen; Schaffzin, Joshua K.

doi:10.1097/inf.0000000000002306

Cited by 10 publications

(4 citation statements)

References 12 publications

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“…20 62 The challenge in eradicating MDR-GNB infection using conventional IV antibiotics results in significant mortality that can be as high as 71.3 to 72.6%, particularly in neonatal ventriculitis after neurosurgical procedures. 6 Recently, uncommon nosocomial infections caused by Veillonella parvula , 25 Elizabethkingia anophelis , 15 E. meningoseptica , 22 Streptococcus gallolyticus subspecies pasteurianus , 23 Candida albicans , 36 Aspergillus fumigatus , 19 and Mycoplasma hominis 21 have been reported in patients with neonatal ventriculitis.…”

Section: Discussionmentioning

confidence: 99%

“…Another search on Google Scholar was performed to identify articles published in non-PubMed indexed journals. Seven publications were found, so we finally reviewed 37 texts (20 case reports, 6 case series, 6 7 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 and 11 original articles 2 3 9 38 39 40 41 42 43 44 45 [5 retrospective and 3 epidemiological surveillance studies, 1 prospective observational study, 1 pilot population pharmacokinetic modeling study, and 1 research article]).…”

Section: Methodsmentioning

confidence: 99%

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Challenges in Diagnosis and Treatment of Neonatal Ventriculitis: A Case Report and Systematic Review of Difficult-to-Treat Central Nervous System Infection Resistant to Conventional Therapy

Ongun,

Kihtir,

Zarif

et al. 2024

J Pediatr Infect Dis

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Objective Ventriculitis is an example of the increasing global trend in difficult-to-treat infections in neonates caused by pathogens resistant to conventional therapies. This article describes the first use of intravenous and intraventricular tigecycline to treat ventriculitis caused by vancomycin-resistant enterococci in a preterm neonate and systematically review the literature on challenges posed by the definitions, diagnosis, and treatment of neonatal ventriculitis Methods The authors searched PubMed and Internet search engines for “ventriculitis” in the period from 2003 to 2023 restricting the research to “Newborn,” “Human,” “English language,” and “full-text availability.” Results Thirty-seven publications (20 case reports, 6 case series, and 11 research articles) were extracted upon research. Preterm birth, posthemorrhagic ventricular dilatation requiring placement of ventricular access devices, and sepsis preceded neonatal ventriculitis. Infections caused by rare microorganisms, in particular gram-negative bacteria resistant to conventional therapies, predominated in the publications describing the need for a combination of intravenous (IV) and intraventricular (IVT) therapies. Survivors of neonatal ventriculitis developed neurodevelopmental impairments such as hydrocephalus, seizures, motor function, hearing, and vision impairment. Conclusion Clinical suspicion of ventriculitis indicated by subtle signs is key for prompt diagnosis. Effective IV and IVT antibiotics are essential to prevent serious sequelae and mortality. The drug delivery method should be changed if there is no clinical response. This study emphasizes the urgent need for pediatric trials of antibiotics against organisms resistant to other drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Challenges in Diagnosis and Treatment of Neonatal Ventriculitis: A Case Report and Systematic Review of Difficult-to-Treat Central Nervous System Infection Resistant to Conventional Therapy

Ongun,

Kihtir,

Zarif

et al. 2024

J Pediatr Infect Dis

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“…showed that isolates possessing the K144R mutation remained fluoroquinolon‐susceptible 38 . This would suggest that the mutation database for genotypic prediction of fluoroquinolone resistance is still incomplete for M. hominis ; however, the absence of mutations may still provide some insight clinically, as demonstrated in a case of M. hominis ventriculitis in a preterm infant that was successfully treated after WGS did not identify any known fluoroquinolone resistance markers 39 …”

Section: Discussionmentioning

confidence: 99%

Mycoplasma hominis infections in solid organ transplant recipients: Clinical characteristics, treatment outcomes, and comparison of phenotypic and genotypic susceptibility profiles

Chang

Price

Beaird

et al. 2022

Transplant Infectious Dis

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Background: Mycoplasma hominis can cause significant infections after solid organ transplantation (SOT). Treatment should be guided by susceptibility testing, but conventional lab methods are laborious with prolonged turnaround time (TAT). This case series compares the phenotypic and genotypic susceptibility profiles of M. hominis isolates identified from SOT patients.Methods: This is a single-center retrospective study evaluating SOT recipients with confirmed M. hominis infections. Patients' demographic, clinical, microbiological, and radiographic data were collected. Culture of M. hominis isolates was performed according to current Clinical and Laboratory Standards Institute guidelines. Phenotypic susceptibility testing was performed by University of Alabama Diagnostic Mycoplasma Laboratory. Whole genome sequencing (WGS) was performed followed by bioinformatic analysis of known genetic determinants of resistance.Results: Seven SOT recipients with M. hominis infections were identified. Two out of seven (28.5%) patients had resistance detected by phenotypic susceptibility testing (Case 5 to levofloxacin and Case 7 to tetracycline). Genomic analyses confirmed the presence of mutations in the parC and parE topoisomerase genes at positions conferring to fluoroquinolone resistance in the isolate from Case 5, while the tetracycline-resistant isolate from Case 7 harbored the tetM gene. The median TAT from the date of specimen collection was 24 days for phenotypic susceptibility testing and 14 days for genotypic susceptibility testing. All seven patients received antimicrobials directed toward M. hominis and recovered with complete resolution of infection.Conclusions: WGS may offer a novel and more rapid methodology for M. hominis susceptibility testing to help optimize antimicrobial usage, but more data are needed.

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“…The in-house samples are available at the NCBI BioSample database (BioProject ID: PRJNA587095), where detailed metadata can be found (see Supplementary Table S1 for sample IDs). Of note, the antimicrobial susceptibility testing with VITEK takes at least 72 h and generally requires a pure isolate, whereas sequencing preparation followed by the WGS data analysis can be completed under 48 h and does need to not rely on a pure colony (Scaggs Huang et al, 2019).…”

Section: Public Data Collectionmentioning

confidence: 99%

Prediction of Antimicrobial Resistance in Gram-Negative Bacteria From Whole-Genome Sequencing Data

2020

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Background: Early detection of antimicrobial resistance in pathogens and prescription of more effective antibiotics is a fast-emerging need in clinical practice. High-throughput sequencing technology, such as whole genome sequencing (WGS), may have the capacity to rapidly guide the clinical decision-making process. The prediction of antimicrobial resistance in Gram-negative bacteria, often the cause of serious systemic infections, is more challenging as genotype-to-phenotype (drug resistance) relationship is more complex than for most Gram-positive organisms. Methods and Findings: We have used NCBI BioSample database to train and crossvalidate eight XGBoost-based machine learning models to predict drug resistance to cefepime, cefotaxime, ceftriaxone, ciprofloxacin, gentamicin, levofloxacin, meropenem, and tobramycin tested in Acinetobacter baumannii, Escherichia coli, Enterobacter cloacae, Klebsiella aerogenes, and Klebsiella pneumoniae. The input is the WGS data in terms of the coverage of known antibiotic resistance genes by shotgun sequencing reads. Models demonstrate high performance and robustness to class imbalanced datasets. Conclusion: Whole genome sequencing enables the prediction of antimicrobial resistance in Gram-negative bacteria. We present a tool that provides an in silico antibiogram for eight drugs. Predictions are accompanied with a reliability index that may further facilitate the decision making process. The demo version of the tool with pre-processed samples is available at https://vancampn.shinyapps.io/wgs2amr/.

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Successful Whole Genome Sequencing-guided Treatment of Mycoplasma hominis Ventriculitis in a Preterm Infant

Cited by 10 publications

References 12 publications

Challenges in Diagnosis and Treatment of Neonatal Ventriculitis: A Case Report and Systematic Review of Difficult-to-Treat Central Nervous System Infection Resistant to Conventional Therapy

Challenges in Diagnosis and Treatment of Neonatal Ventriculitis: A Case Report and Systematic Review of Difficult-to-Treat Central Nervous System Infection Resistant to Conventional Therapy

Mycoplasma hominis infections in solid organ transplant recipients: Clinical characteristics, treatment outcomes, and comparison of phenotypic and genotypic susceptibility profiles

Prediction of Antimicrobial Resistance in Gram-Negative Bacteria From Whole-Genome Sequencing Data

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