Serum-Associated Antibiotic Tolerance in Pediatric Clinical Isolates of <i>Pseudomonas aeruginosa</i>

Morrison, John M.; Chojnacki, Michaelle; Fadrowski, Jeffrey J.; Bauza, Colleen; Dunman, Paul M.; Dudas, Robert A.; Goldenberg, Neil A.; Berman, David M.

doi:10.1093/jpids/piz094

Cited by 9 publications

(9 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…On the other hand, the MBEC 80 of pre-formed P. aeruginosa biofilms grown in FBS and IVWM was determined to be 8 μg/mL, an 8-fold increase compared to LB. The presence of serum is known to increase antimicrobial tolerance [ [104] , [105] , [106] ], owing to the serum-binding properties of certain antibiotics, including binding of tobramycin and serum albumin [ 107 ]. However, this increased tolerance could also be due to the inherent biofilm properties under these conditions, including nutrient distribution and variations in microbial metabolism [ 108 ].…”

Section: Resultsmentioning

confidence: 99%

Milieu matters: An in vitro wound milieu to recapitulate key features of, and probe new insights into, mixed-species bacterial biofilms

Kadam

Vandana

Dhekane

et al. 2021

Biofilm

View full text Add to dashboard Cite

Bacterial biofilms are a major cause of delayed wound healing. Consequently, the study of wound biofilms, particularly in host-relevant conditions, has gained importance. Most in vitro studies employ refined laboratory media to study biofilms, representing conditions that are not relevant to the infection state. To mimic the wound milieu, in vitro biofilm studies often incorporate serum or plasma in growth conditions, or employ clot or matrix-based biofilm models. While incorporating serum or plasma alone is a minimalistic approach, the more complex in vitro wound models are technically demanding, and poorly compatible with standard biofilm assays. Based on previous reports of clinical wound fluid composition, we have developed an in vitro wound milieu (IVWM) that includes, in addition to serum (to recapitulate wound fluid), matrix elements and biochemical factors. With Luria-Bertani broth and Fetal Bovine Serum (FBS) for comparison, the IVWM was used to study planktonic growth, biofilm features, and interspecies interactions, of common wound pathogens, Staphylococcus aureus and Pseudomonas aeruginosa . We demonstrate that the IVWM recapitulates widely reported in vivo biofilm features such as biomass formation, metabolic activity, increased antibiotic tolerance, 3D structure, and interspecies interactions for monospecies and mixed-species biofilms. Further, the IVWM is simple to formulate, uses laboratory-grade components, and is compatible with standard biofilm assays. Given this, it holds potential as a tractable approach to study wound biofilms under host-relevant conditions.

show abstract

Section: Resultsmentioning

confidence: 99%

Milieu matters: An in vitro wound milieu to recapitulate key features of, and probe new insights into, mixed-species bacterial biofilms

Kadam

Vandana

Dhekane

et al. 2021

Biofilm

View full text Add to dashboard Cite

show abstract

“…However, in zinc-depleted media, more analogous to human zinc concentrations, these organisms are more sensitive to carbapenems and better predict in vivo outcomes ( 40 ). Conversely, Morrison et al ( 41 ) demonstrated among respiratory and blood Pseudomona s aeruginosa isolates recovered from pediatric patients that some had lower aminoglycoside and minocycline MICs in traditional medium than in serum-based media. The impact of these newly identified conditional differences in MIC on the patient PK/PD response has not been identified, but this is an area of further interest to study.…”

Section: Pathogen Minimum Inhibitory Concentration and Its Impact On Tdmmentioning

confidence: 99%

β-Lactam Therapeutic Drug Monitoring in Critically Ill Patients: Weighing the Challenges and Opportunities to Assess Clinical Value

Dilworth

Schulz

Micek

et al. 2022

Critical Care Explorations

View full text Add to dashboard Cite

OBJECTIVE: β-lactams are the cornerstone of empiric and targeted antibiotic therapy for critically ill patients. Recently, there have been calls to use β-lactam therapeutic drug monitoring (TDM) within 24–48 hours after the initiation of therapy in critically ill patients. In this article, we review the dynamic physiology of critically ill patients, β-lactam dose response in critically ill patients, the impact of pathogen minimum inhibitory concentration (MIC) on β-lactam TDM, and pharmacokinetics in critically ill patients. Additionally, we highlight available clinical data to better inform β-lactam TDM for critically ill patients. DATA SOURCES: We retrospectively analyzed patients admitted for sepsis or septic shock at a single academic medical center who were treated with β-lactam antibiotics. STUDY SELECTION: Indexed studies in PubMed in English language were selected for review on topics relative to critical care physiology, β-lactams, pharmacokinetics/pharmacodynamics, TDM, and antibiotic susceptibility. DATA EXTRACTION: We reviewed potentially related studies on β-lactams and TDM and summarized their design, patients, and results. This is a synthetic, nonsystematic, review. DATA SYNTHESIS: In the retrospective analysis of patients treated with β-lactam antibiotics, approximately one-third of patients received less than 48 hours of β-lactam therapy. Of those who continued beyond 48 hours, only 13.7% had patient-specific factors (augmented renal clearance, fluid overload, morbid obesity, and/or surgical drain), suggesting a potential benefit of β-lactam TDM. CONCLUSIONS: These data indicate that a strategy of comprehensive β-lactam TDM for critically ill patients is unwarranted as it has not been shown yet to improve patient-oriented outcomes. This review demonstrates that β-lactam TDM in the ICU, while laudable, layers ambiguous β-lactam exposure thresholds upon uncertain/unknown MIC data within a dynamic, unpredictable patient population for whom TDM results will not be available fast enough to significantly affect care. Judicious, targeted TDM for those with risk factors for β-lactam over- or underexposure is a better approach but requires further study. Clinically, choosing the correct antibiotic and dosing β-lactams aggressively, which have a wide therapeutic index, to overcome critical illness factors appears to give critically ill patients the best likelihood of survival.

show abstract

“…On the other hand, the MBEC 80 of preformed P. aeruginosa biofilms grown in FBS and IVWM was determined to be 8 µg/mL, an 8-fold increase compared to LB. While the presence of serum is known to increase antimicrobial tolerance [101][102][103], owing to the serum-binding properties of certain antibiotics, including binding of tobramycin and serum albumin [104], this increased tolerance could also be due to the inherent properties of the biofilm formed under these conditions. The similarity of MBEC 80 in FBS and IVWM (which contains 70% FBS) could possibly indicate the dominant role of serum in influencing the antibiotic tolerance of P. aeruginosa biofilms.…”

Section: Antibiotic Susceptibility Of P Aeruginosa and S Aureus Biomentioning

confidence: 99%

Milieu matters: Anin vitrowound milieu to recapitulate key features of, and probe new insights into, polymicrobial biofilms

Kadam

Vandana

Bhide

et al. 2021

Preprint

View full text Add to dashboard Cite

Bacterial biofilms are a major cause of delayed wound healing. Consequently, the study of wound biofilms, particularly in host-relevant conditions, has gained importance. Most in vitro biofilm studies employ refined laboratory media to study biofilms, conditions that are not relevant to the infection state. To mimic the wound milieu, in vitro biofilm studies often incorporate serum or plasma in growth conditions, or employ clot or matrix-based biofilm models. While incorporating serum or plasma alone is a minimalistic approach, the more complex in vitro wound models are technically demanding, and poorly compatible with standard biofilm assays. Based on previous reports of clinical wound fluid composition, we have developed an in vitro wound milieu (IVWM) that includes, in addition to serum (to recapitulate wound fluid), matrix elements and biochemical factors. In comparison with Luria-Bertani broth and Fetal Bovine Serum (FBS), the IVWM was used to study planktonic growth and biofilm features, including interspecies interactions, of common wound pathogens, Staphylococcus aureus and Pseudomonas aeruginosa. We demonstrate that the IVWM recapitulates widely reported in vivo biofilm features such as metabolic activity, increased antibiotic tolerance, 3D structure, and interspecies interactions for single- and co-species biofilms. Further, the IVWM is simple to formulate, uses laboratory-grade components, and is compatible with standard biofilm assays. Given this, it holds potential as a tractable approach to study wound biofilms under host-relevant conditions.

show abstract

Serum-Associated Antibiotic Tolerance in Pediatric Clinical Isolates of Pseudomonas aeruginosa

Cited by 9 publications

References 36 publications

Milieu matters: An in vitro wound milieu to recapitulate key features of, and probe new insights into, mixed-species bacterial biofilms

Milieu matters: An in vitro wound milieu to recapitulate key features of, and probe new insights into, mixed-species bacterial biofilms

β-Lactam Therapeutic Drug Monitoring in Critically Ill Patients: Weighing the Challenges and Opportunities to Assess Clinical Value

Milieu matters: Anin vitrowound milieu to recapitulate key features of, and probe new insights into, polymicrobial biofilms

Contact Info

Product

Resources

About