In vitro antagonism by erythromycin of the bactericidal action of antimicrobial agents against common respiratory pathogens

Cohn, John R.; Jungkind, Donald; Baker, J S

doi:10.1128/aac.18.6.872

Cited by 9 publications

(5 citation statements)

References 16 publications

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“…This observation suggests that when the antibiotics are used together, the more slowly acting bactericidal agent, vancomycin, may have the potential to antagonize the more rapid bactericidal effect of oxacillin, negating the anticipated benefit of the ␤-lactam. Such in vitro antagonism has been demonstrated when ß-lactams are combined with bacteriostatic agents such as erythromycin (8). In the present study, we sought to evaluate the interactions between vancomycin and oxacillin against clinical isolates of MSSA.…”

mentioning

confidence: 99%

Lack of Bactericidal Antagonism or SynergismIn Vitrobetween Oxacillin and Vancomycin against Methicillin-Susceptible Strains ofStaphylococcus aureus

Joukhadar

Pillai

Wennersten

et al. 2010

Antimicrob Agents Chemother

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With the current high prevalence of infection caused by methicillin-resistant Staphylococcus aureus (MRSA) strains but in light of the general belief that ␤-lactam antibiotics are more effective than vancomycin against infections caused by methicillin-susceptible S. aureus (MSSA) isolates, clinicians may utilize antistaphylococcal penicillins in combination with vancomycin for the empirical treatment of S. aureus infections. Vancomycin is considered to kill MSSA more slowly than oxacillin. Thus, we sought to evaluate the interaction of the combination of oxacillin and vancomycin on bacterial killing in vitro. Ten clinical isolates of MSSA isolated in the year 2000 were investigated. The killing observed at 24 h by vancomycin at 20 g/ml, oxacillin at 16 g/ml, or the combination did not differ (approximately 2.5 to 3.5 log 10 CFU/ml). In a separate experiment, we assessed bacterial killing in a dynamic model simulating the free plasma concentration profiles expected following the administration of a combination of vancomycin at 1 g every 12 h and oxacillin at 1 g every 6 h. The time-kill profiles of these regimens against S. aureus ATCC 29213 were comparable to those observed in the fixed-concentration experiments. Using these methods, we found no evidence that vancomycin antagonized the bactericidal effect of oxacillin or that there was any benefit from use of the combination.In many clinical settings, methicillin-resistant Staphylococcus aureus (MRSA) strains comprise such a high proportion of the S. aureus isolates that empirical treatment with vancomycin is begun when a staphylococcal infection is suspected (10, 18). However, several studies have reported that for infections due to methicillin-susceptible S. aureus (MSSA) strains, treatment with ␤-lactam antibiotics results in clinical outcomes better than those achieved with vancomycin (15, 18). For this reason, some clinicians use vancomycin and a ␤-lactam together as empirical treatment, both to provide adequate coverage for MRSA and in the belief that the ␤-lactam would provide superior antimicrobial activity should the organism prove to be methicillin susceptible.Small and Chambers (17) reported that vancomycin killed MSSA more slowly than nafcillin when they used time-kill methods. This observation suggests that when the antibiotics are used together, the more slowly acting bactericidal agent, vancomycin, may have the potential to antagonize the more rapid bactericidal effect of oxacillin, negating the anticipated benefit of the ␤-lactam. Such in vitro antagonism has been demonstrated when ß-lactams are combined with bacteriostatic agents such as erythromycin (8). In the present study, we sought to evaluate the interactions between vancomycin and oxacillin against clinical isolates of MSSA.(Part of the data presented here were presented at the 49th Interscience Conference on Antimicrobial Agents and Chemo- MATERIALS AND METHODSBacterial strains. The clinical MSSA isolates tested in part A of the present study were A8115, A8117, A8561, A8562, A8564, A856...

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confidence: 99%

Lack of Bactericidal Antagonism or SynergismIn Vitrobetween Oxacillin and Vancomycin against Methicillin-Susceptible Strains ofStaphylococcus aureus

Joukhadar

Pillai

Wennersten

et al. 2010

Antimicrob Agents Chemother

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“…30 Control checkerboard assays were also run to rule out any potential synergies between the unvectorized compound 41 and erythromycin or between the vector itself, kanamycin, and erythromycin. 37 On E. coli K1 wild strain, the MIC of erythromycin remained at 16 μg/mL independent of the concentration of 41 (0−32 μg/mL). On the same strain, kanamycin alone displayed a MIC of 8 μg/mL, while it demonstrated a pure additive effect in combination with erythromycin.…”

Section: ■ Results and Discussionmentioning

confidence: 98%

“…Control experiments were run to assess that the kanamycin moiety did not impart any antibacterial activity in 9 at these doses . Control checkerboard assays were also run to rule out any potential synergies between the unvectorized compound 41 and erythromycin or between the vector itself, kanamycin, and erythromycin . On E. coli K1 wild strain, the MIC of erythromycin remained at 16 μg/mL independent of the concentration of 41 (0–32 μg/mL).…”

Section: Resultsmentioning

confidence: 99%

Vectorization Efforts To Increase Gram-Negative Intracellular Drug Concentration: A Case Study on HldE-K Inhibitors

et al. 2013

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In this paper, we present different strategies to vectorize HldE kinase inhibitors with the goal to improve their gram-negative intracellular concentration. Syntheses and biological effects of siderophoric, aminoglycosidic, amphoteric, and polycationic vectors are discussed. While siderophoric and amphoteric vectorization efforts proved to be disappointing in this series, aminoglycosidic and polycationic vectors were able for the first time to achieve synergistic effects of our inhibitors with erythromycin. Although these effects proved to be nonspecific, this study provides information about the required stereoelectronic arrangement of the polycationic amines and their basicity requirements to fulfill outer membrane destabilization resulting in better erythromycin synergies.

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“…Although data is available for erythromycin, this interaction may theoretically occur with other macrolides. According to the literature, there is no need to take any special precaution other than monitoring the effectiveness of treatment for this interaction (28)(29)(30).…”

Section: Discussionmentioning

confidence: 99%

The Importance of Computerized Drug Interaction Checker Programs Used in Community Pharmacies to Avoid Potential Drug Interactions: A Preliminary Study with Clarithromycin

Şimşek¹,

Taner²,

Macit³

et al. 2019

Istanbul Med J

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Amaç: Çoklu ilaç kullanımına bağlı olarak gelişen ilaç-ilaç etkileşimleri (DDI) advers ilaç reaksiyonlarının en önemli nedenidir. İlaç hatalarından bir tanesi olarak sayılan DDI önlenebilir. Sağlık profesyonellerinin tıbbi ve pratik bilgilerinin yanında kullanacakları entegre bilgisayarlı ilaç etkileşimi kontrol sistemleri, tek başlarına yeterli olmamakla beraber olası etkileşimlerin azaltılması için sağlık personeline yardımcı olabilir. Bu çalışmada ayaktan pediatri hastalarına reçete edilen klaritromisin ile potansiyel DDI'ların (PDDI) belirlenmesi ve önlenmesinde bilgisayarlı ilaç etkileşimi kontrol sistemlerinin rolünün araştırılması amaçlanmıştır. Yöntemler: Retrospektif gözlemsel reçete analizi niteliğinde olan bu çalışmada, 12 aylık periyotta (Ocak-Aralık 2016) pediatrik ayaktan hastalara solunum yolu enfeksiyonu tanısı ile oral klaritromisin yazılan reçeteler İstanbul ili Üsküdar ilçesinde faaliyet gösteren ve çalışmaya katılmayı kabul eden, üç serbest eczaneden toplanarak müstahzar isim ve sayıları ile hasta demografik verileri (yaş, cinsiyet) kayıt edildi. PDDI'lar etkin madde bazında R x MediaPharma® programı ile tespit analiz edildi. Bulgular: On iki aylık periyotta 52 farklı hekim tarafından 266 adet müstahzarın reçetelendiği 100 adet reçete toplanmış olup, reçete başına ortalama müstahzar sayısı 2,66±1,11 idi. Tespit edilen 16 PDDI'nın 5'i klaritromisin (%31,25) ve 11 tanesi klaritromisin dışı (%68,75) idi. PDDI'lar şiddet bazında kategorize edildiğinde, toplam 16 etkileşimden 10 tanesi (%62,5) yüksek, 2 tanesi (%12,5) orta ve 4'ü (%25) düşük idi. Klaritromisin etkileşimleri ise: Lidokain ile orta; metronidazol ve sultamisin (ampisilin/sulbaktam) ile ise minör kategorisinde idi. Sonuç: Hızlı erişim imkanı sağlayan bilgisayarlı ilaç etkileşimi kontrol sistemleri tek başlarına yeterli olmamakla beraber PDDI'ların önlenmesinde sağlık personeline yardımcı olabilir. Bu sistemlerin serbest eczanelerde kullanımı ilacın hastaya verilmesi esnasında yaşanacak olan DDI'ların önlenmesinde oldukça önem taşımaktadır. Anahtar Kelimeler: İlaç etkileşimi, bilgisayarlı ilaç etkileşimi kontrol programı, advers ilaç reaksiyonları Introduction: Drug-drug interactions (DDI) due to multiple drug use are the most important cause of adverse drug reactions. DDIs are among medication errors that can be prevented. The integrated computerized drug interaction checker programs, which medical professionals use in addition to their medical and practical knowledge, can help medical staff to reduce potential DDIs (PDDIs), although they are not sufficient alone. The aim of this study was to investigate the role of computerized drug interaction checker programs in the identification and prevention of PDDIs in clarithromycin prescribed pediatric outpatients. Methods: The study was a retrospective observational prescription analysis held in three community pharmacies operating in the province of Üsküdar-İstanbul during 12-month period. The prescriptions with oral clarithromycin medication were selected and PDDIs were analyzed using the ...

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In vitro antagonism by erythromycin of the bactericidal action of antimicrobial agents against common respiratory pathogens

Cited by 9 publications

References 16 publications

Lack of Bactericidal Antagonism or SynergismIn Vitrobetween Oxacillin and Vancomycin against Methicillin-Susceptible Strains ofStaphylococcus aureus

Lack of Bactericidal Antagonism or SynergismIn Vitrobetween Oxacillin and Vancomycin against Methicillin-Susceptible Strains ofStaphylococcus aureus

Vectorization Efforts To Increase Gram-Negative Intracellular Drug Concentration: A Case Study on HldE-K Inhibitors

The Importance of Computerized Drug Interaction Checker Programs Used in Community Pharmacies to Avoid Potential Drug Interactions: A Preliminary Study with Clarithromycin

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