Antagonism by chloramphenicol of broad-spectrum beta-lactam antibiotics against Klebsiella pneumoniae

Brown, Timothyh .; Alford, R H

doi:10.1128/aac.25.4.405

Cited by 16 publications

(13 citation statements)

References 16 publications

(17 reference statements)

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“…The authors found antagonism between chloramphenicol and the five analyzed betalactams [128]. Similarly, an antagonism was found with ceftriaxone against enteric Gram-negative rods [129] and with gentamicin against isolates of Escherichia coli and Bacteroides fragilis [133,134]. Regarding penicillin G, a synergistic bactericidal effect with chloramphenicol was observed in 17 out of 20 beta-lactamase-producing strains of S. aureus.…”

Section: Enterobacter Sppmentioning

confidence: 86%

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Could chloramphenicol be used against ESKAPE pathogens? A review ofin vitrodata in the literature from the 21st century

Čivljak

Giannella

Bella

et al. 2014

Expert Review of Anti-infective Therapy

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The widespread use of antibiotics has been associated with the emergence of antimicrobial resistance among bacteria. 'ESKAPE' (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acintobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) pathogens play a major role in the rapidly changing scenario of antimicrobial resistance in the 21st century. Chloramphenicol is a broad spectrum antibiotic that was abandoned in developed countries due to its association with fatal aplastic anemia. However, it is still widely used in the developing world. In light of the emerging problem of multi-drug resistant pathogens, its role should be reassessed. Our paper reviews in vitro data on the activity of chloramphenicol against ESKAPE pathogens. Susceptibility patterns for Gram-positives were good, although less favorable for Gram-negatives. However, in combination with colistin, chloramphenicol was found to have synergistic activity. The risk-benefit related to chloramphenicol toxicity has not been analyzed. Therefore, extra precautions should be taken when prescribing this agent.

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Section: Enterobacter Sppmentioning

confidence: 86%

“…A summary of the in vitro results with various drug combinations is presented inTABLE 7. Most of these studies are old, did not test ESKAPE microorganisms and may not provide currently relevant information[120][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135][136][137][138].…”

mentioning

confidence: 99%

Could chloramphenicol be used against ESKAPE pathogens? A review ofin vitrodata in the literature from the 21st century

Čivljak

Giannella

Bella

et al. 2014

Expert Review of Anti-infective Therapy

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“…Overall, synergism has been demonstrated in combinations of imipenem with aminoglycosides against enterococci (3,8,10,24) and Listeria monocytogenes (8) and less frequently against staphylococci, enteric gram-negative bacteria, and nonfermentative bacteria (7,11,14,18,19). Conversely, imipenem has shown antagonistic interactions with other ,-lactam antimicrobial agents against Pseudomonas aeruginosa (1,4,25) and Serratia marcescens (17) and with chloramphenicol against Klebsiella pneumoniae (6).…”

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confidence: 99%

In vitro activity of imipenem against enterococci and staphylococci and evidence for high rates of synergism with teicoplanin, fosfomycin, and rifampin

Debbia¹,

Varaldo²,

Schito³

1986

Antimicrob Agents Chemother

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The in vitro activities of imipenem alone and in combination with teicoplanin, fosfomycin, and rifampin were tested against clinical isolates of enterococci and staphylococci. In both groups of organisms, the three combinations demonstrated high rates of synergism in both checkerboard ahd time-kill studies.Imipenem is the first clinically useful member of the carbapenems, a new class of antimicrobial agents that are unique among ,-lactams both for their chemical structure and because of their extraordinarily broad antibacterial spectrum. Since its development from thienamycin as the N-formimidoyl derivative, imipenem has been studied extensively in recent years, and the data available about its in vitro antibacterial activity have been reviewed repeatedly (5,12,13,16). However, in this series of studies, investigations of its interactions with other antimicrobial agents are relatively limited. Overall, synergism has been demonstrated in combinations of imipenem with aminoglycosides against enterococci (3, 8, 10, 24) and Listeria monocytogenes (8) and less frequently against staphylococci, enteric gram-negative bacteria, and nonfermentative bacteria (7,11,14,18,19). Conversely, imipenem has shown antagonistic interactions with other ,-lactam antimicrobial agents against Pseudomonas aeruginosa (1,4, 25) and Serratia marcescens (17) and with chloramphenicol against Klebsiella pneumoniae (6).In this study, enterococcal and staphylococcal strains freshly isolated from clinical material were tested for susceptibility to imipenem, teicoplanin, fosfomycin, and rifampin. Interactions between imipenem and each of the three other antimicrobial agents were then determined both by checkerboard titration and by time-kill curves.Enterococci were identified as Streptococcus faecalis (71 isolates) or Streptococcus faecium (10 isolates) on the basis of standard criteria. Staphylococci were identified on the basis of lytic activity patterns (23) and other conventional tests, and their susceptibility to methicillin was preliminarily determnined by agar diffusion on plates of Mueller-Hinton agar (Difco Laboratories, Detroit, Mich.) supplemented with 5% NaCl. Staphylococcal strains were subdivided into Staphylococcus aureus (38 isolates, of which 16 were methicillin resistant), Staphylococcus epidermidis (18 isolates, of which 7 were methicillin resistant), and Staphylococcus sp. (17 isolates, of which 6 were methicillin resistant, belonging to other coagulase-negative species).Antimicrobial agents were supplied as follows: imipenem, Merck Sharp & Dohme Italia, Rome, Italy; teicoplanin and rifampin, Gruppo Lepetit, Milan, Italy; and fosfomycin, Zambon, Milan, Italy.The MICs and MBCs of the four antimicrobial agents were determined for all isolates from broth dilutions in microtiter * Corresponding author. trays with Mueller-Hinton broth (Difco) as the test medium. Twofold dilutions of each drug, prepared so as to obtain final concentrations ranging from 0.004 to 64 ,ug/ml, were made with a hand-held multidilution device that delive...

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“…The use of antibiotic combinations to treat bacterial infections is increasingly common, but the predictability of this approach is limited (9,10). It is well-known that bacteriostaticbactericidal combination treatments result in attenuation of bactericidal activity in vitro across a range of drugs and organisms (11)(12)(13)(14)(15)(16)(17)(18). Clinically, this effect can have negative consequences in high morbidity infections like meningitis (19,20), or positive effects by inhibiting lysis and exotoxin release in toxin-mediated syndromes (21,22).…”

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confidence: 99%

Antibiotic efficacy is linked to bacterial cellular respiration

Lobritz

Belenky

Porter

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

592

548

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Bacteriostatic and bactericidal antibiotic treatments result in two fundamentally different phenotypic outcomes-the inhibition of bacterial growth or, alternatively, cell death. Most antibiotics inhibit processes that are major consumers of cellular energy output, suggesting that antibiotic treatment may have important downstream consequences on bacterial metabolism. We hypothesized that the specific metabolic effects of bacteriostatic and bactericidal antibiotics contribute to their overall efficacy. We leveraged the opposing phenotypes of bacteriostatic and bactericidal drugs in combination to investigate their activity. Growth inhibition from bacteriostatic antibiotics was associated with suppressed cellular respiration whereas cell death from most bactericidal antibiotics was associated with accelerated respiration. In combination, suppression of cellular respiration by the bacteriostatic antibiotic was the dominant effect, blocking bactericidal killing. Global metabolic profiling of bacteriostatic antibiotic treatment revealed that accumulation of metabolites involved in specific drug target activity was linked to the buildup of energy metabolites that feed the electron transport chain. Inhibition of cellular respiration by knockout of the cytochrome oxidases was sufficient to attenuate bactericidal lethality whereas acceleration of basal respiration by genetically uncoupling ATP synthesis from electron transport resulted in potentiation of the killing effect of bactericidal antibiotics. This work identifies a link between antibiotic-induced cellular respiration and bactericidal lethality and demonstrates that bactericidal activity can be arrested by attenuated respiration and potentiated by accelerated respiration. Our data collectively show that antibiotics perturb the metabolic state of bacteria and that the metabolic state of bacteria impacts antibiotic efficacy.

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Antagonism by chloramphenicol of broad-spectrum beta-lactam antibiotics against Klebsiella pneumoniae

Cited by 16 publications

References 16 publications

Could chloramphenicol be used against ESKAPE pathogens? A review ofin vitrodata in the literature from the 21st century

Could chloramphenicol be used against ESKAPE pathogens? A review ofin vitrodata in the literature from the 21st century

In vitro activity of imipenem against enterococci and staphylococci and evidence for high rates of synergism with teicoplanin, fosfomycin, and rifampin

Antibiotic efficacy is linked to bacterial cellular respiration

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