Single versus combination intravenous anti-pseudomonal antibiotic therapy for people with cystic fibrosis

Abstract

Single versus combination intravenous anti-pseudomonal antibiotic therapy for people with cystic fibrosis (Review)Elphick HE, Scott A Elphick HE, Scott A. Single versus combination intravenous anti-pseudomonal antibiotic therapy for people with cystic fibrosis.

Pseudomonas aeruginosa antimicrobial susceptibility test (AST) results and pulmonary exacerbation treatment responses in cystic fibrosis

“…Our analyses also assessed associations of β-lactam and aminoglycoside co-administration and antifungal co-administration on treatment outcomes, with neither found to be associated with differences in treatment response (Supplemental Figures S2 and S3). The former observation is consistent with a Cochrane review of the subject [14] but in contradiction to common P. aeruginosa treatment practice in the CF community. We have separated outcomes for treatments with "indeterminant" Pa coverage, in which at least one antimicrobial was not included in AST or for which there were no established AST interpretive criteria (e.g., inhaled antimicrobials).…”

Pseudomonas aeruginosa antimicrobial susceptibility test (AST) results and pulmonary exacerbation treatment responses in cystic fibrosis

“…Our analyses also assessed associations of β-lactam and aminoglycoside co-administration and antifungal co-administration on treatment outcomes, with neither found to be associated with differences in treatment response (Supplemental Figures S2 and S3). The former observation is consistent with a Cochrane review of the subject [14] but in contradiction to common P. aeruginosa treatment practice in the CF community. We have separated outcomes for treatments with "indeterminant" Pa coverage, in which at least one antimicrobial was not included in AST or for which there were no established AST interpretive criteria (e.g., inhaled antimicrobials).…”

Mutational background influences P. aeruginosa ciprofloxacin resistance evolution but preserves collateral sensitivity robustness

“…Therefore, our results support that it might be possible to exploit CS associated with ciprofloxacin-resistance acquisition to design evolution-based approaches to tackle P. aeruginosa infections containing preexisting antibiotic-resistant mutants. In this regard, it is worth mentioning that blind—not evolutionary-based—clinical trials of antibiotic combinations for fighting P. aeruginosa infections are regularly performed ( 65 ), while rational evolutionary-based information, as the results presented here, supporting these trials are generally absent. However, we are aware that testing the proposed treatments in different infection models, as well as confirming the robustness of CS in clinical strains of P. aeruginosa , presenting different genomic backgrounds, not just different mutational backgrounds, would also be needed for the translation of the results into clinical practice.…”

Aminoglycoside dosing and monitoring for Pseudomonas aeruginosa during acute pulmonary exacerbations in cystic fibrosis

“…In addition, six of the eight studies included were completed before 1988, and therefore before the discovery of the CFTR gene when CF standards of care were much different. There were no significant differences observed between monotherapy and combination treatment groups in lung function parameters, adverse events, symptom scores, or resistance 57 . Potential benefits of combination therapy include synergy between the aminoglycoside and beta‐lactam, and a potential for decreased resistance as monotherapy may select for resistant strains of PsA .…”

Pseudomonas aeruginosa antimicrobial susceptibility test (AST) results and pulmonary exacerbation treatment responses in cystic fibrosis

“…Our analyses also assessed associations of β-lactam and aminoglycoside co-administration and antifungal co-administration on treatment outcomes, with neither found to be associated with differences in treatment response (Supplemental Figures S2 and S3). The former observation is consistent with a Cochrane review of the subject [14] but in contradiction to common P. aeruginosa treatment practice in the CF community. We have separated outcomes for treatments with "indeterminant" Pa coverage, in which at least one antimicrobial was not included in AST or for which there were no established AST interpretive criteria (e.g., inhaled antimicrobials).…”

Mutational background influences P. aeruginosa ciprofloxacin resistance evolution but preserves collateral sensitivity robustness

“…Therefore, our results support that it might be possible to exploit CS associated with ciprofloxacin-resistance acquisition to design evolution-based approaches to tackle P. aeruginosa infections containing preexisting antibiotic-resistant mutants. In this regard, it is worth mentioning that blind—not evolutionary-based—clinical trials of antibiotic combinations for fighting P. aeruginosa infections are regularly performed ( 65 ), while rational evolutionary-based information, as the results presented here, supporting these trials are generally absent. However, we are aware that testing the proposed treatments in different infection models, as well as confirming the robustness of CS in clinical strains of P. aeruginosa , presenting different genomic backgrounds, not just different mutational backgrounds, would also be needed for the translation of the results into clinical practice.…”

Aminoglycoside dosing and monitoring for Pseudomonas aeruginosa during acute pulmonary exacerbations in cystic fibrosis

“…In addition, six of the eight studies included were completed before 1988, and therefore before the discovery of the CFTR gene when CF standards of care were much different. There were no significant differences observed between monotherapy and combination treatment groups in lung function parameters, adverse events, symptom scores, or resistance 57 . Potential benefits of combination therapy include synergy between the aminoglycoside and beta‐lactam, and a potential for decreased resistance as monotherapy may select for resistant strains of PsA .…”

Pseudomonas aeruginosa antimicrobial susceptibility test (AST) results and pulmonary exacerbation treatment responses in cystic fibrosis

“…Our analyses also assessed associations of β-lactam and aminoglycoside co-administration and antifungal co-administration on treatment outcomes, with neither found to be associated with differences in treatment response (Supplemental Figures S2 and S3). The former observation is consistent with a Cochrane review of the subject [14] but in contradiction to common P. aeruginosa treatment practice in the CF community. We have separated outcomes for treatments with "indeterminant" Pa coverage, in which at least one antimicrobial was not included in AST or for which there were no established AST interpretive criteria (e.g., inhaled antimicrobials).…”

Mutational background influences P. aeruginosa ciprofloxacin resistance evolution but preserves collateral sensitivity robustness

“…Therefore, our results support that it might be possible to exploit CS associated with ciprofloxacin-resistance acquisition to design evolution-based approaches to tackle P. aeruginosa infections containing preexisting antibiotic-resistant mutants. In this regard, it is worth mentioning that blind—not evolutionary-based—clinical trials of antibiotic combinations for fighting P. aeruginosa infections are regularly performed ( 65 ), while rational evolutionary-based information, as the results presented here, supporting these trials are generally absent. However, we are aware that testing the proposed treatments in different infection models, as well as confirming the robustness of CS in clinical strains of P. aeruginosa , presenting different genomic backgrounds, not just different mutational backgrounds, would also be needed for the translation of the results into clinical practice.…”

Aminoglycoside dosing and monitoring for Pseudomonas aeruginosa during acute pulmonary exacerbations in cystic fibrosis

“…In addition, six of the eight studies included were completed before 1988, and therefore before the discovery of the CFTR gene when CF standards of care were much different. There were no significant differences observed between monotherapy and combination treatment groups in lung function parameters, adverse events, symptom scores, or resistance 57 . Potential benefits of combination therapy include synergy between the aminoglycoside and beta‐lactam, and a potential for decreased resistance as monotherapy may select for resistant strains of PsA .…”