Evaluating Mono- and Combination Therapy of Meropenem and Amikacin against Pseudomonas aeruginosa Bacteremia in the Hollow-Fiber Infection Model
ABSTRACT Debate continues as to the role of combination antibiotic therapy for the management of Pseudomonas aeruginosa infections. We studied the extent of bacterial killing by and the emergence of resistance to meropenem and amikacin as monotherapies and as a combination therapy against susceptibl...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2022-06-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00525-22 |
| _version_ | 1818255559628947456 |
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| author | Minyon L. Avent Kate L. McCarthy Fekade B. Sime Saiyuri Naicker Aaron J. Heffernan Steven C. Wallis David L. Paterson Jason A. Roberts |
| author_facet | Minyon L. Avent Kate L. McCarthy Fekade B. Sime Saiyuri Naicker Aaron J. Heffernan Steven C. Wallis David L. Paterson Jason A. Roberts |
| author_sort | Minyon L. Avent |
| collection | DOAJ |
| description | ABSTRACT Debate continues as to the role of combination antibiotic therapy for the management of Pseudomonas aeruginosa infections. We studied the extent of bacterial killing by and the emergence of resistance to meropenem and amikacin as monotherapies and as a combination therapy against susceptible and resistant P. aeruginosa isolates from bacteremic patients using the dynamic in vitro hollow-fiber infection model. Three P. aeruginosa isolates (meropenem MICs of 0.125, 0.25, and 64 mg/L) were used, simulating bacteremia with an initial inoculum of ~1 × 105 CFU/mL and the expected pharmacokinetics of meropenem and amikacin in critically ill patients. For isolates susceptible to amikacin and meropenem (isolates 1 and 2), the extent of bacterial killing was increased with the combination regimen compared with the killing by monotherapy of either antibiotic. Both the combination and meropenem monotherapy were able to sustain bacterial killing throughout the 7-day treatment course, whereas regrowth of bacteria occurred with amikacin monotherapy after 12 h. For the meropenem-resistant P. aeruginosa isolate (isolate 3), only the combination regimen demonstrated bacterial killing. Given that tailored antibiotic regimens can maximize potential synergy against some isolates, future studies should explore the benefit of combination therapy against resistant P. aeruginosa. IMPORTANCE Current guidelines recommend that aminoglycosides should be used in combination with β-lactam antibiotics as initial empirical therapy for serious infections, and otherwise, patients should receive β-lactam antibiotic monotherapy. Given the challenges associated with studying the clinical effect of different antibiotic strategies on patient outcomes, useful data for subsequent informed clinical testing can be obtained from in vitro models like the hollow-fiber infection model (HFIM). Based on the findings of our HFIM, we propose that the initial use of combination therapy with meropenem and amikacin provides some bacterial killing against carbapenem-resistant P. aeruginosa isolates. For susceptible isolates, combination therapy may only be of benefit in specific patient populations, such as critically ill or immunocompromised patients. Therefore, clinicians may want to consider using the combination therapy for the initial management and ceasing the aminoglycosides once antibiotic susceptibility results have been obtained. |
| first_indexed | 2024-12-12T17:13:47Z |
| format | Article |
| id | doaj.art-d1397707952648dd858c2688ff506f91 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-12-12T17:13:47Z |
| publishDate | 2022-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-d1397707952648dd858c2688ff506f912022-12-22T00:17:50ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-06-0110310.1128/spectrum.00525-22Evaluating Mono- and Combination Therapy of Meropenem and Amikacin against Pseudomonas aeruginosa Bacteremia in the Hollow-Fiber Infection ModelMinyon L. Avent0Kate L. McCarthy1Fekade B. Sime2Saiyuri Naicker3Aaron J. Heffernan4Steven C. Wallis5David L. Paterson6Jason A. Roberts7The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, AustraliaThe University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, AustraliaThe University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, AustraliaThe University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, AustraliaThe University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, AustraliaThe University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, AustraliaThe University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, AustraliaThe University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, AustraliaABSTRACT Debate continues as to the role of combination antibiotic therapy for the management of Pseudomonas aeruginosa infections. We studied the extent of bacterial killing by and the emergence of resistance to meropenem and amikacin as monotherapies and as a combination therapy against susceptible and resistant P. aeruginosa isolates from bacteremic patients using the dynamic in vitro hollow-fiber infection model. Three P. aeruginosa isolates (meropenem MICs of 0.125, 0.25, and 64 mg/L) were used, simulating bacteremia with an initial inoculum of ~1 × 105 CFU/mL and the expected pharmacokinetics of meropenem and amikacin in critically ill patients. For isolates susceptible to amikacin and meropenem (isolates 1 and 2), the extent of bacterial killing was increased with the combination regimen compared with the killing by monotherapy of either antibiotic. Both the combination and meropenem monotherapy were able to sustain bacterial killing throughout the 7-day treatment course, whereas regrowth of bacteria occurred with amikacin monotherapy after 12 h. For the meropenem-resistant P. aeruginosa isolate (isolate 3), only the combination regimen demonstrated bacterial killing. Given that tailored antibiotic regimens can maximize potential synergy against some isolates, future studies should explore the benefit of combination therapy against resistant P. aeruginosa. IMPORTANCE Current guidelines recommend that aminoglycosides should be used in combination with β-lactam antibiotics as initial empirical therapy for serious infections, and otherwise, patients should receive β-lactam antibiotic monotherapy. Given the challenges associated with studying the clinical effect of different antibiotic strategies on patient outcomes, useful data for subsequent informed clinical testing can be obtained from in vitro models like the hollow-fiber infection model (HFIM). Based on the findings of our HFIM, we propose that the initial use of combination therapy with meropenem and amikacin provides some bacterial killing against carbapenem-resistant P. aeruginosa isolates. For susceptible isolates, combination therapy may only be of benefit in specific patient populations, such as critically ill or immunocompromised patients. Therefore, clinicians may want to consider using the combination therapy for the initial management and ceasing the aminoglycosides once antibiotic susceptibility results have been obtained.https://journals.asm.org/doi/10.1128/spectrum.00525-22amikacinmeropenemPseudomonas aeruginosapharmacodynamichollow fiber infection model |
| spellingShingle | Minyon L. Avent Kate L. McCarthy Fekade B. Sime Saiyuri Naicker Aaron J. Heffernan Steven C. Wallis David L. Paterson Jason A. Roberts Evaluating Mono- and Combination Therapy of Meropenem and Amikacin against Pseudomonas aeruginosa Bacteremia in the Hollow-Fiber Infection Model Microbiology Spectrum amikacin meropenem Pseudomonas aeruginosa pharmacodynamic hollow fiber infection model |
| title | Evaluating Mono- and Combination Therapy of Meropenem and Amikacin against Pseudomonas aeruginosa Bacteremia in the Hollow-Fiber Infection Model |
| title_full | Evaluating Mono- and Combination Therapy of Meropenem and Amikacin against Pseudomonas aeruginosa Bacteremia in the Hollow-Fiber Infection Model |
| title_fullStr | Evaluating Mono- and Combination Therapy of Meropenem and Amikacin against Pseudomonas aeruginosa Bacteremia in the Hollow-Fiber Infection Model |
| title_full_unstemmed | Evaluating Mono- and Combination Therapy of Meropenem and Amikacin against Pseudomonas aeruginosa Bacteremia in the Hollow-Fiber Infection Model |
| title_short | Evaluating Mono- and Combination Therapy of Meropenem and Amikacin against Pseudomonas aeruginosa Bacteremia in the Hollow-Fiber Infection Model |
| title_sort | evaluating mono and combination therapy of meropenem and amikacin against pseudomonas aeruginosa bacteremia in the hollow fiber infection model |
| topic | amikacin meropenem Pseudomonas aeruginosa pharmacodynamic hollow fiber infection model |
| url | https://journals.asm.org/doi/10.1128/spectrum.00525-22 |
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