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Targeting MRSA in Cystic Fibrosis: Ceftaroline-Meropenem Combination Therapy and the Predictive Role of PrsA

Award Number: R21AI202371
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Targeting MRSA in Cystic Fibrosis: Ceftaroline-Meropenem Combination Therapy and the Predictive Role of PrsA - PROJECT SUMMARY Cystic Fibrosis (CF) is an autosomal recessive disorder caused by CFTR gene mutations affecting a cAMP-activated chloride channel. While CFTR modulators have improved outcomes, airway infections remain a major challenge. Methicillin-Resistant Staphylococcus aureus (MRSA) is a common infection in people with CF (PwCF) and difficult to treat due to rapid antibiotic resistance. The CF Patient Registry 2023 reports that chronic suppressive therapy for Pseudomonas aeruginosa infections has significantly improved outcomes, including better lung function and fewer exacerbations. However, this progress has led to a rise in MRSA infections. Chronic MRSA infection is linked to faster declines in lung function and increased early mortality in PwCF. Given these challenges, continued investigation of chronic MRSA suppression is essential. Currently, no effective suppressive treatments exist. Recent trials of inhaled dry powder vancomycin were ineffective and caused bronchospasm in some study subjects. Ceftaroline a potent fifth-generation cephalosporin, is often a drug of last resort. Our team and others found Ceftaroline resistance in MRSA isolates without prior ceftaroline exposure. This resistance is prevalent in PwCF, where prior carbapenem use for Pseudomonas aeruginosa infections compromises ceftaroline efficacy. Our lab has discovered that combining ceftaroline with meropenem restores efficacy against high-level ceftaroline-resistant MRSA. This combination therapy may also prevent Pseudomonas emergence during MRSA suppression. This synergy exploits genetic vulnerabilities and disrupts PBP2a membrane localization via PrsA dysfunction. Our specific aims are: Aim 1: To optimize CPT/MER dosing via PK/PD and evaluate combination efficacy in chronic MRSA with/without CFTR modulators. Aim 2: To define PrsA’s role in CPT/MER synergy and assess its potential as a predictive biomarker in CF-MRSA. The proposed studies address a critical unmet need by innovatively repurposing existing antibiotics to treat chronic MRSA infections in people with cystic fibrosis (PwCF), while also uncovering resistance mechanisms that will enable biomarker-guided precision therapy.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $489,848 )
2026	2026	MAINEHEALTH	110 FREE ST	PORTLAND	ME	04101	CUMBERLAND	USA	Allergy and Infectious Diseases Research	000	1	8/26/2026	NEW	$489,848
														Subtotal = $489,848

Grand Total All Awards = $489,848

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Targeting MRSA in Cystic Fibrosis: Ceftaroline-Meropenem Combination Therapy and the Predictive Role of PrsA

Award Number: R21AI202371

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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