In vitro selection of resistance in Pseudomonas aeruginosa and Acinetobacter spp. by levofloxacin and ciprofloxacin alone and in combination with β-lactams and amikacin

Drago, Lorenzo; Vecchi, Elena De; Nicola, L.; Tocalli, Loredana; Gismondo, Maria Rita

doi:10.1093/jac/dki204

Cited by 30 publications

(20 citation statements)

References 38 publications

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“…Recent studies also showed that the combination of a fluoroquinolone with a beta-lactam had in vitro and in vivo synergy against extended-spectrum betalactamase-producing Escherichia coli and P. aeruginosa isolates, respectively (8,22). This combination contributed less frequently than did monotherapy to in vitro selection for resistance in three different gram-negative bacilli (8,9).…”

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confidence: 99%

β-Lactam and Fluoroquinolone Combination Antibiotic Therapy for Bacteremia Caused by Gram-Negative Bacilli

Al-Hasan

Wilson

Lahr³

et al. 2009

Antimicrob Agents Chemother

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The role of combination antibiotic therapy with a beta-lactam and a fluoroquinolone for bacteremia caused by gram-negative bacilli, to our knowledge, has not been previously described. Much of the previous study of combination therapy has included beta-lactams and aminoglycosides. We conducted a large retrospective cohort study to evaluate 28-day all-cause mortality in patients with monomicrobial bacteremia due to aerobic gram-negative bacilli who received either a combination of beta-lactams and fluoroquinolones or beta-lactam monotherapy. We enrolled adult patients admitted to Mayo Clinic hospitals from 1 January 2001 to 31 October 2006 in the study. After stratification of patients by Pitt bacteremia scores, we used Cox regression models to estimate the hazard ratios (HR) for 28-day all-cause mortality after adjusting for the propensity to receive combination therapy. We identified 398 and 304 unique patients with bacteremia caused by gram-negative bacilli who received single and combination antibiotic therapy, respectively. In less severely ill patients with Pitt bacteremia scores of <4, combination therapy was associated with lower 28-day mortality than single therapy The efficacy of combination antimicrobial therapy in patients with bacteremia caused by gram-negative bacilli has been previously examined. The majority of studies have included beta-lactam and aminoglycoside antibiotic combinations. Overall, there was no significant reduction in mortality with beta-lactam and aminoglycoside combinations compared to beta-lactam monotherapy in patients with bacteremia caused by gram-negative bacilli (16,18,25). However, decreased mortality was demonstrated in subgroups of patients with Pseudomonas aeruginosa bacteremia (4, 14, 25) and critically ill patients with Klebsiella species bacteremia (17). A clinical benefit with combination therapy was also seen in neutropenic patients with bacteremia caused by gram-negative bacilli (10, 18). As a result, beta-lactam and aminoglycoside combination therapy has been frequently used in patients with P. aeruginosa bacteremia, but not in patients with bacteremia due to other gram-negative bacilli (6). This approach is particularly useful in patients with risk factors for P. aeruginosa bacteremia for whom combination therapy is started empirically; otherwise, there is little benefit if the decision to start combination therapy is delayed until a gram-negative organism in blood cultures is identified (4,14,15). In addition, due to the potential drug-related adverse events associated with aminoglycosides in critically ill patients, particularly nephrotoxicity, empirical use of these drugs has been limited (21,26).With the increase in antibiotic resistance among gram-negative bacilli, use of combination antibiotic therapy for bacteremia caused by gram-negative bacilli has reemerged. Studies have shown that inappropriate antimicrobial treatment can be reduced with empirical administration of combination therapy (19). Despite the increasing use of fluoroquinolones due to their r...

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confidence: 99%

β-Lactam and Fluoroquinolone Combination Antibiotic Therapy for Bacteremia Caused by Gram-Negative Bacilli

Al-Hasan

Wilson

Lahr³

et al. 2009

Antimicrob Agents Chemother

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“…The highest synergy was seen in beta-lactam-fluoroquinolone and fluoroquinolone-AK combinations. 24 While in a study conducted in 2011, Tan et al 8 detected rate of synergy by CB method between polymyxin B-RF and TGC-RF as 19%, those between polymyxin B-TGC was 12%. The same rates obtained by TK methods were 56%, 19% and 44% respectively.…”

Section: Discussionmentioning

confidence: 98%

Antibiotic Resistance Profiles and Genotypes of <i>Acinetobacter baumannii</i> Isolates and <i>In Vitro</i> Interactions of Various Antibiotics in Combination with Tigecycline and Colistin

Büyük

Yılmaz

Yurtsever

et al. 2017

tjps

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ÖZAmaç: Bu çalışmada nozokomiyal çoklu ilaç dirençli (ÇİD) Acinetobacter baumannii izolatlarının antibiyotik direnç profilinin belirlenmesi, moleküler düzeyde tiplendirmelerinin yapılması ve dirençli izolatlarda antibiyotik kombinasyonlarının aktivitesinin araştırılması amaçlandı. Gereç ve Yöntemler: Seksen dört ÇİD A. baumannii izolatına karşı tigesiklin (TGC), kolistin (CL), amikasin (AK), siprofloksasin (CIP), meropenem (MR), moksifloksasin (MXF) ve rifampisinin (RF) minimum inhibitör konsantrasyon (MİK) değerleri sıvı mikrodilüsyon yöntemi ile belirlendi. Epidemiyolojik ilişki, AP-PZR ve antibiyotiplendirme ile saptandı. Klonal ilişkisiz kökenlere antibiyotik kombinasyonlarının etkinliği dama tahtası (CB) yöntemi ile belirlendi. Dama tahtası yöntemi sonucunda, en etkin gözlenen kombinasyonun etkinliği, seçilmiş bir kökene karşı zamana bağlı öldürme eğrisi (TK) yöntemi ile de araştırıldı. Bulgular: CIP, RF, MXF, MR, AK'nin direnç oranları sırasıyla; %90.47; %47.62; %22.62; %58.33; %50 olarak belirlendi. TGC ve CL direnci görülmedi. Antibiyotik direnç profillerine göre 25 antibiyotip grubu belirlenirken, 15 farklı patern ayırt edildi. Klonal ilişkisiz 15 ÇİD A. baumannii izolatında CB yöntemiyle en iyi sinerjistik etki CL-RF (%100), CL-MR (%100) ve TGC-RF (%53) kombinasyonlarında gözlendi. Seçilmiş bir kökende TK yöntemiyle CL-RF ve CL-MR ile sinerji gözlendi, TGC-RF ile ise aditif etki saptandı. Sonuç: Bu çalışmada her iki sinerji testi de ÇİD A. baumannii izolatlarına karşı CL ile RF kombinasyonunun tedavide iyi bir seçim olacağını işaret etmiştir. Anahtar kelimeler: Acinetobacter, AP-PZR, dama tahtası, zamana bağlı öldürme eğrisi, tigesiklin, kolistin Objectives: The aim of this study was to determine the antibiotic resistance profile, clonal relation and efficacy of antibiotic combinations in nosocomial multidrug resistant (MDR) Acinetobacter baumannii. Materials and Methods: Antibiotic susceptibilities of 84 MDR A. baumannii against tigecycline (TGC), colistin (CL), amikacin (AK), ciprofloxacin (CIP), meropenem (MR), moxifloxacin (MXF), rifampicin (RF) were determined by microdilution method. Clonal relationship was investigated by genotyping using AP-PCR and antibiotyping. Interactions of antibiotic combinations were tested against clonally unrelated strains by the checkerboard (CB) method. The efficacy of the best combinations was also assesed on a selected isolate by the time-kill (TK) method. Results: CIP, RF, MXF, MR, AK resistance was found as 90.47%; 47.62%; 22.62%; 58.33%; 50% respectively; however; CL and TGC were not ascertained. The isolates were distinguished as 25 different antibiotypes and 15 varied molecular patterns. The best synergistic effect was detected in combinations of CL with RF (100%) and MR (100%), in combinations of TGC with RF (53%) against clonally unrelated 15 MDR A. baumannii isolates by the CB method. While CL-RF and CL-MR showed synergy by TK method like CB, on the other hand TGC-RF indicated additive interactions by TK. Conclusion: In this study, both synergy tests showed...

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“…20,21,[25][26][27][28] We demonstrated that amikacin, gentamicin, or vancomycin can be delivered from the calcium sulfate dihydrate FAST pellets with effective dissolution and elution profiles. All FAST pellet formulations completely dissolved and eluted antibiotics in 12-24 h, whereas only 50% of the conventional pellet flakes had dissolved and 99.3% of antibiotic was released within this time frame.…”

Section: Discussionmentioning

confidence: 99%

Preliminary in vitro evaluation of an adjunctive therapy for extremity wound infection reduction: Rapidly resorbing local antibiotic delivery

Jackson

Richelsoph

Courtney

et al. 2008

Journal Orthopaedic Research

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Despite the continuing advances in treatment of open fractures and musculoskeletal wounds, infection remains a serious complication. Current treatments to prevent infection utilize surgical debridement and irrigation, and high doses of systemic antimicrobial therapy. The aim of this work was to evaluate, in vitro, the potential of a fast-resorbing calcium sulfate pellet loaded with an antibiotic. The pellet could be used as an adjunctive therapy at the time of debridement and irrigation to reduce bacterial wound contamination. Small pellets containing a binder and calcium sulfate were engineered to resorb rapidly (within 24 h) and deliver high local doses of antibiotic (amikacin, gentamicin, or vancomycin) to the wound site while minimizing systemic effects. Results from dissolution, elution, and biological activity tests against P. aeruginosa and S. aureus were used to compare the performance of antibiotic-loaded, rapidly resorbing calcium sulfate pellets to antibiotic-loaded crushed conventional calcium sulfate pellets. Antibiotic-loaded rapidly resorbing pellets dissolved in vitro in deionized water in 12-16 h and released therapeutic antibiotic levels in phosphate buffered saline that were above the minimal inhibitory concentration for P. aeruginosa and S. aureus, completely inhibiting the growth of these bacteria for the life of the pellet. Crushed conventional calcium sulfate pellets dissolved over 4-6 days, but the eluates only contained sufficient antibiotic to inhibit growth for the first 4 h. These data indicate that fast-resorbing pellets can release antibiotics rapidly and at therapeutic levels. Adjunctive therapy with fast-acting pellets is promising and warrants further in vivo studies. ß

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In vitro selection of resistance in Pseudomonas aeruginosa and Acinetobacter spp. by levofloxacin and ciprofloxacin alone and in combination with β-lactams and amikacin

Abstract: Use of combinations of fluoroquinolones with beta-lactams and amikacin reduces the risk for in vitro selection of resistant P. aeruginosa and Acinetobacter spp.

Cited by 30 publications

References 38 publications

β-Lactam and Fluoroquinolone Combination Antibiotic Therapy for Bacteremia Caused by Gram-Negative Bacilli

β-Lactam and Fluoroquinolone Combination Antibiotic Therapy for Bacteremia Caused by Gram-Negative Bacilli

Antibiotic Resistance Profiles and Genotypes of <i>Acinetobacter baumannii</i> Isolates and <i>In Vitro</i> Interactions of Various Antibiotics in Combination with Tigecycline and Colistin

Preliminary in vitro evaluation of an adjunctive therapy for extremity wound infection reduction: Rapidly resorbing local antibiotic delivery

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