Evaluation of the E test for the assessment of synergy of antibiotic combinations against multiresistant Pseudomonas aeruginosa isolates from cystic fibrosis patients

Balke, B.; Hogardt, Michael; Schmoldt, Sabine; Hoy, L.; Weißbrodt, H.; Häußler, Susanne

doi:10.1007/s10096-005-0076-9

Cited by 30 publications

(16 citation statements)

References 41 publications

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“…These two studies reflect the consensus of others who have compared synergy methods for different antimicrobial combinations and bacterial species and all found the same thing, that no two synergy methods produce comparable results (14)(15)(16)(17). However, in some circumstances, Ͼ90% correlation between Etest and checkerboard testing has been observed (18).…”

Section: Comparison Of Synergy Testing Methodssupporting

confidence: 75%

When Does 2 Plus 2 Equal 5? A Review of Antimicrobial Synergy Testing

2014

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In this age of emerging antibiotic resistance, limited therapeutic options exist for treating multidrug-resistant organisms. Combination therapy is commonly employed to manage these infections despite little laboratory guidance as to the efficacy of this approach. Synergy testing methods have been used to assess the interaction of antibiotic combinations in vitro. This review will discuss the four primary methods used to assess synergy, as well as the data that exist for testing of cystic fibrosis. In the final analysis, this review concludes that there is not enough evidence to endorse synergy testing for routine clinical use.

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Section: Comparison Of Synergy Testing Methodssupporting

confidence: 75%

When Does 2 Plus 2 Equal 5? A Review of Antimicrobial Synergy Testing

2014

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“…Combination therapy is a subject of intense interest, since the emergence of MDR pathogens often requires us to treat patients with more than one antibiotic (7,32,49,53,54,108,146,169,226). A list of the antibiotic combinations which have been tested in vitro against common MDR organisms and their effects is presented in Table 1.…”

Section: In the Beginning…mentioning

confidence: 99%

Carbapenems: Past, Present, and Future

Papp-Wallace

Endimiani

Taracila

et al. 2011

Antimicrob Agents Chemother

1,115

962

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In this review, we summarize the current "state of the art" of carbapenem antibiotics and their role in our antimicrobial armamentarium. Among the ␤-lactams currently available, carbapenems are unique because they are relatively resistant to hydrolysis by most ␤-lactamases, in some cases act as "slow substrates" or inhibitors of ␤-lactamases, and still target penicillin binding proteins. This "value-added feature" of inhibiting ␤-lactamases serves as a major rationale for expansion of this class of ␤-lactams. We describe the initial discovery and development of the carbapenem family of ␤-lactams. Of the early carbapenems evaluated, thienamycin demonstrated the greatest antimicrobial activity and became the parent compound for all subsequent carbapenems. To date, more than 80 compounds with mostly improved antimicrobial properties, compared to those of thienamycin, are described in the literature. We also highlight important features of the carbapenems that are presently in clinical use: imipenem-cilastatin, meropenem, ertapenem, doripenem, panipenem-betamipron, and biapenem. In closing, we emphasize some major challenges and urge the medicinal chemist to continue development of these versatile and potent compounds, as they have served us well for more than 3 decades.Carbapenems play a critically important role in our antibiotic armamentarium. Of the many hundreds of different ␤-lactams, carbapenems possess the broadest spectrum of activity and greatest potency against Gram-positive and Gram-negative bacteria. As a result, they are often used as "last-line agents" or "antibiotics of last resort" when patients with infections become gravely ill or are suspected of harboring resistant bacteria (23,(174)(175)(176)229). Unfortunately, the recent emergence of multidrug-resistant (MDR) pathogens seriously threatens this class of lifesaving drugs (189). Several recent studies clearly show that resistance to carbapenems is increasing throughout the world (35,64,73,123,151,155,173,200). Despite this menacing trend, our understanding of how to best use these agents is undergoing a renaissance, especially concerning their role with regard to ␤-lactamase inhibition. In this context, we view the number, type, and diversity of carbapenems as compelling reasons to explore these compounds for new insights into drug development.

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“…In the past, studies that used checkerboard methods showed that carbapenem-plus-aminoglycoside combinations were synergistic against P. aeruginosa; however, limited or no information on suppression of resistance and the type of synergy was provided (20)(21)(22)(23)(24)(25)(26). A few SCTK combination studies demonstrated that combinations (a ␤-lactam plus an aminoglycoside) are beneficial (14,27,28) but also reported extensive regrowth at 24 h (28).…”

Section: Yadav Et Al Antimicrobial Agents and Chemotherapymentioning

confidence: 99%

Optimization of Synergistic Combination Regimens against Carbapenem- and Aminoglycoside-Resistant Clinical Pseudomonas aeruginosa Isolates via Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling

Yadav

Bulitta

Nation

et al. 2017

Antimicrob Agents Chemother

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Optimizing antibiotic combinations is promising to combat multidrugresistant Pseudomonas aeruginosa. This study aimed to systematically evaluate synergistic bacterial killing and prevention of resistance by carbapenem and aminoglycoside combinations and to rationally optimize combination dosage regimens via a mechanism-based mathematical model (MBM). We studied monotherapies and combinations of imipenem with tobramycin or amikacin against three difficult-to-treat double-resistant clinical P. aeruginosa isolates. Viable-count profiles of total and resistant populations were quantified in 48-h static-concentration time-kill studies (inoculum, 10 7.5 CFU/ml). We rationally optimized combination dosage regimens via MBM and Monte Carlo simulations against isolate FADDI-PA088 (MIC of imipenem [MIC imipenem ] of 16 mg/liter and MIC tobramycin of 32 mg/liter, i.e., both 98th percentiles according to the EUCAST database). Against this isolate, imipenem (1.5ϫ MIC) combined with 1 to 2 mg/liter tobramycin (MIC, 32 mg/liter) or amikacin (MIC, 4 mg/liter) yielded Ն2-log 10 more killing than the most active monotherapy at 48 h and prevented resistance. For all three strains, synergistic killing without resistance was achieved by Ն0.88ϫ MIC imipenem in combination with a median of 0.75ϫ MIC tobramycin (range, 0.032ϫ to 2.0ϫ MIC tobramycin ) or 0.50ϫ MIC amikacin (range, 0.25ϫ to 0.50ϫ MIC amikacin ). The MBM indicated that aminoglycosides significantly enhanced the imipenem target site concentration up to 3-fold; achieving 50% of this synergistic effect required aminoglycoside concentrations of 1.34 mg/liter (if the aminoglycoside MIC was 4 mg/liter) and 4.88 mg/liter (for MICs of 8 to 32 mg/liter). An optimized combination regimen (continuous infusion of imipenem at 5 g/day plus a 0.5-h infusion with 7 mg/kg of body weight tobramycin) was predicted to achieve Ͼ2.0-log 10 killing and prevent regrowth at 48 h in 90.3% of patients (median bacterial killing, Ͼ4.0 log 10 CFU/ml) against double-resistant isolate FADDI-PA088 and therefore was highly promising.

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Evaluation of the E test for the assessment of synergy of antibiotic combinations against multiresistant Pseudomonas aeruginosa isolates from cystic fibrosis patients

Cited by 30 publications

References 41 publications

When Does 2 Plus 2 Equal 5? A Review of Antimicrobial Synergy Testing

When Does 2 Plus 2 Equal 5? A Review of Antimicrobial Synergy Testing

Carbapenems: Past, Present, and Future

Optimization of Synergistic Combination Regimens against Carbapenem- and Aminoglycoside-Resistant Clinical Pseudomonas aeruginosa Isolates via Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling

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