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Antagonistic effect of chloramphenicol in combination with cefotaxime or ceftriaxone
Antimicrobial Agents and Chemotherapy
Abstract
We evaluated the in vitro interaction at clinically attainable concentrations of cefotaxime and ceftriaxone with chloramphenicol
against 26 clinical isolates of gram-negative rods, group B streptococci, and Staphylococcus aureus. Cefotaxime and ceftriaxone
were bactericidal against all 26 organisms (MBC, 0.03 to 4 micrograms/ml). Chloramphenicol was bacteriostatic against 24 organisms
(MBC, greater than or equal to 32 micrograms/ml) and bactericidal against two Escherichia coli isolates (MBC, 8 micrograms/ml).
Checkerboard testing showed chloramphenicol to be antagonistic to the bactericidal activity of cefotaxime and ceftriaxone
for all 24 bacteria for which chloramphenicol was bacteriostatic. Time kill curves for selected strains of E. coli and group
B streptococci for which chloramphenicol was bacteriostatic showed antagonism of chloramphenicol to both cephalosporins. The
combination of chloramphenicol with either cephalosporin was antagonistic in cases in which chloramphenicol was bacteriostatic
against the above organisms and should be avoided in the treatment of infections caused by such organisms if bactericidal
therapy is desired.
... However, its overall killing effects were slower than those of CRO alone when tested at the same concentrations. This paradoxical phenomenon might be due to the bacteriostatic effect of AZT that inhibits the required exponential growth of gonococcus for the adequate mechanism of action of CRO (37,38). This type of antagonistic effect was not recorded by calculating the FICIs, but it was instead clearly indicated from the killing curves obtained for ATCC 49226 and the clinical N. gonorrhoeae strain AE-7570 of ST1407: the bactericidal action was more rapid for AZT plus CRO at 0.5ϫ the MICs than at 4ϫ the MIC (Fig. 2). ...
... The addition of AZT did not antagonize the effect of FOS, as was indicated for CRO. Although both FOS and CRO inhibit cell wall synthesis, FOS is a concentration-dependent antibiotic (18)(19)(20)27), whereas CRO is a time-dependent drug that is probably more affected by the decline in exponential growth determined by AZT and other bacteriostatic antibiotics (37,38,42). ...
New therapeutic strategies are needed to combat the emergence of infections due to multidrug-resistant Neisseria gonorrhoeae (Ng). In this study, fosfomycin (FOS) was tested against 89 Ng using the Etest method and showing MIC50/90s of only 8/16 μg/ml (range ≤ 1-32 μg/ml). FOS in combination with ceftriaxone (CRO) or azithromycin (AZT) was then evaluated using the checkerboard method for eight strains, including F89 (CRO-resistant) and AZT-HLR (high-level AZT-resistant). All combinations including FOS gave indifferent effects (fractional inhibitory concentration [FIC] index values between 1.2-2.3 for FOS plus CRO and between 1.8-3.2 for FOS plus AZT). Time-kill experiments for FOS, CRO, AZT and their combinations (at concentrations of 0.5×, 1×, 2× and 4× MIC) were performed against ATCC 49226, one Ng of NG-MAST ST1407, F89 and AZT-HLR. For all strains, at 24 hours results indicated that: i) FOS was bactericidal at 2× MIC concentrations but after >24 hours there was re-growth of bacteria; ii) CRO was bactericidal at 0.5× MIC; iii) AZT was bactericidal at 4× MIC; iv) CRO plus AZT was less bactericidal than CRO alone; v) FOS plus AZT was bactericidal at 2× MIC; vi) CRO plus AZT and FOS plus CRO were both bactericidal at 0.5× MIC, but the latter had more rapid effects. FOS is appealing for the management of Ng infections because of its single and oral formulation. However, our results suggest its use in combination with CRO. This strategy could, after appropriate clinical trials, be implemented for the treatment of infections due to isolates possessing resistance to CRO and/or AZT.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
... In contrast, when some cephalosporins such as cefotaxime and ceftriaxone are co-administrated with chloramphenicol, detrimental outcomes can result. For instance, it was reported in a study that co-administrating chloramphenicol at 8 μg/mL with cephalosporin resulted in a significant increase in the minimum bactericidal concentration (MBC) of Cephalosporin (0.28-21.5 μg/mL) [23]. Therefore, careful consideration of combination treatment is warranted. ...
While the global market for veterinary products has been expanding rapidly, there is still a lack of specialist knowledge of equine pharmaceutics. In many cases, the basic structure of the gastrointestinal tract (GIT) and integumentary system of the horse shares similarities with those of humans. Generally, the dosage form developed for humans can be repurposed to deliver equine medications; however, due to physiological variation, the therapeutic outcomes can be unpredictable. This is an area that requires more research, as there is a clear deficiency in literature precedence on drug delivery specifically for horses. Through a careful evaluation of equine anatomy and physiology, novel drug delivery systems (NDDSs) can be developed to adequately address many of the medical ailments of the horse. In addition to this, there are key considerations when delivering oral, topical, and parenteral drugs to horses, deriving from age and species variation. More importantly, NDDSs can enhance the duration of action of active drugs in animals, significantly improving owner compliance; and ultimately, enhancing the convenience of product administration. To address the knowledge gap in equine pharmaceutical formulations, this paper begins with a summary of the anatomy and physiology of the equine gastrointestinal, integumentary, and circulatory systems. A detailed discussion of potential dosage-form related issues affecting horses, and how they can be overcome by employing NDDSs is presented.
... The antibacterial effect of cefotaxime has been shown to decrease in combination with other agents. Chloramphenicol as a bacterial agent reduced cefotaxime activity in 26 clinical isolates of Gram-negative rods, group B streptococci, and Staphylococcus aureus (Asmar and Dajani, 1988). Cefotaxime activity against 24 Propionibacterium acne strains also decreased as a result of the antagonistic action of linezolide, cipro oxacin or clindamycin (Mory et al., 2005). ...
Pyocyanin (PCN) is a blue–green pigment mainly produced by Pseudomonas aeruginosa. It has antimicrobial effects on a variety of organisms. Ampicillin (AMP) and cefotaxime (CTX) are widely used against bacterial pathogens as important antibacterial agents. The effect of PCN on the antibacterial action of AMP and CTX has been studied. PCN from P. aeruginosa was extracted by chloroform method. Two PCN concentrations (2 and 4 µg/ml) were combined separately with a variety of AMP and CTX concentrations. Change in the antibacterial activity of AMP and CTX against 14 isolated pathogenic bacteria after combination has been investigated. The antibacterial activity of AMP decreased against 7 bacterial isolates when mixed with 4 µg/ml of PCN, while this activity increased against the majority of bacteria after mixing with 2 µg/ml. CTX activity was also reduced against 12 bacterial isolates by 4 µg/ml of PCN, while it was not generally affected by 2 µg/ml. in conclusion; PCN had variable effects on the antibacterial activity of AMP and CTX, which varied mainly between decreased activity and absence of effects. A low concentration of PCN was more effective in increasing the action of AMP, but had no effect on the action of CTX.
... Antagonism between various b-lactams and protein synthesis inhibitors has been widely documented (e.g. 67,68 ). LaPlante and Sakoulas 69 have investigated the potential antagonism of different anti-Grampositive agents to aztreonam against E. coli in vitro. ...
The monobactam aztreonam is currently being re-examined as a therapeutic agent in light of the global spread of carbapenem
resistance in aerobic Gram-negative bacilli and aztreonam's stability to Ambler class B metallo-β-lactamases. Of particular
interest are the pharmacokinetic and pharmacodynamic properties of aztreonam alone and in combination with β-lactamase inhibitors.
The choice of inhibitor may vary depending on the spectrum of β-lactamases produced by Enterobacteriaceae. The monobactam
ring is also being used to produce new developmental monobactams. Thus, a greater understanding of aztreonam pharmacokinetics
and dynamics is of great relevance in drug development. This review summarizes the pharmacokinetic profile of aztreonam in
man and its pharmacodynamics in human and pre-clinical studies when studied alone and with β-lactamase inhibitors.
... Les phénicolés exercent in vitro un antagonisme sur l'effet bactéricide de certains antibiotiques tels que les b-lactamines et les aminoglycosides [3] ; par ailleurs, le triméthoprime et le sulfaméthoxazole exercent dans certains modèles une inhibition de l'effet bactériostatique du chloramphénicol [4] . Même si la pertinence clinique de ces travaux reste à démontrer, l'administration conjointe de ces molécules doit probablement être évitée. ...
... Les phénicolés exercent in vitro un antagonisme sur l'effet bactéricide de certains antibiotiques tels que les b-lactamines et les aminoglycosides [3] ; par ailleurs, le triméthoprime et le sulfaméthoxazole exercent dans certains modèles une inhibition de l'effet bactériostatique du chloramphénicol [4] . Même si la pertinence clinique de ces travaux reste à démontrer, l'administration conjointe de ces molécules doit probablement être évitée. ...
Los fenicoles (cloranfenicol y tianfenicol) pertenecen a una familia de fármacos que apareció hace más de 60 años. Sus ventajas (espectro muy amplio, buena biodisponibilidad, excelente difusión tisular en el parénquima cerebral infectado) se han ido eclipsando debido a su toxicidad hematológica (en particular la infrecuente pero gravísima anemia aplásica irreversible debida al cloranfenicol) y, en menor medida, debido a la aparición de resistencias. Aunque sigue siendo un antibiótico de primera línea en el tratamiento de las meningococias y la fiebre tifoidea en los países en vías de desarrollo (cloranfenicol), su utilización en los países con un alto nivel sanitario está limitada a una indicación importante (tianfenicol), el absceso cerebral no documentado, y eventualmente como molécula de recurso en diversas infecciones, como las rickettsiosis.
... Linezolid demonstrates minimal activity against gram-negative bacteria, so an explanation for worse outcomes in patients receiving linezolid is not obvious (22). However, there are cases of documented antagonism between beta-lactam agents and chloramphenicol, a drug similar to linezolid, by mechanisms of action (binding to domain V of the 50S subunit of rRNA) and resistance mechanisms (1,12,17,19,27,28). Therefore, it is practical to hypothesize that beta-lactam agents may be antagonized in the presence of linezolid or other protein synthesis inhibitors. ...
In an in vitro pharmacodynamic model, linezolid attenuated the activity of aztreonam and ceftazidime against Escherichia coli. Conversely, synergy was detected at 24 and 48 h when daptomycin or vancomycin was added to aztreonam and ceftazidime. We
conclude that significant yet underappreciated interactions may occur between gram-positive-spectrum and gram-negative-spectrum
antibacterials.
Der Liquor cerebrospinalis ist pharmakologisch ein tiefes Kompartiment, in dem Wirkstoffe verspätet und mit geringerer Konzentration als im Blutplasma auftreten. Die Schwankungen der Liquorgängigkeit und Konzentration handelsüblicher Antibiotika sind dadurch bedingt, daβ die Penetration in den Liquorraum vom Entzündungsgrad der Meningen abhängig ist und daβ die Wirkstoffe sich innerhalb des Liquorraumes ungleichmäβig verteilen. Selbst die intrathekale Applikationsweise führt nicht zu einer gleichmäβigen Konzentrationsverteilung der Antibiotika.
Latar belakang. Masalah resistensi antibiotik di Indonesia sudah mengkhawatirkan. Penggunaan antibiotik
secara bijak merupakan kunci utama pengendalian resistensi.
Tujuan. Penelitian bertujuan meneliti faktor-faktor yang mempengaruhi kualitas penggunaan antibiotik
di Bangsal Kesehatan Anak RS Dr. Kariadi dan menguji apakah kualitas dapat ditingkatkan dengan
pelatihan.
Metode. One group pretest and post test subjek adalah 22 dokter yang merawat pasien kelas III, mengikuti
pelatihan penggunaan antibiotik, dan dapat ditelusuri resep antibiotik yang dibuatnya dalam 6 bulan
sebelum dan sesudah pelatihan. Variabel tergantung adalah skor kualitas penggunaan antibiotik berdasarkan
modifikasi Kunin dan Gyssen. Variabel bebas adalah pelatihan, pengetahuan, sikap, faktor pendorong, dan
faktor penghambat. Pengetahuan dan sikap diukur dengan kuesioner. Analisis statistik bivariat menggunakan
Uji χ2 dan Mann-Whitney. Analisis multivariat untuk mengukur besarnya pengaruh pelatihan dan faktorfaktor
lain terhadap kualitas peresepan antibiotik dengan GEE.
Hasil. Diantara 1365 resep antibiotik yang dievaluasi didapatkan penggunaan antibiotik tanpa indikasi setelah
pelatihan berkurang dari 42.3% menjadi 23,2%, dan penggunaan antibiotik yang tepat meningkat dari 36,2%
menjadi 58,2%. Rerata skor kualitas pengunaan antibiotik meningkat dari 2,0 menjadi 2,8. Perubahanperubahan
ini bermakna (p
Background
In this study, we check for the presence of specific resistance genes by polymerase chain reaction (PCR) and then we used flow cytometry (FCM) to evaluate antibiotic-induced effects in different strains of Escherichia coli (E. coli).Methods
The presence of resistance genes was investigated by PCR in 10 strains of E. coli isolated from Foglia River. Bacterial responses to different antibiotics were also tested with FCM techniques by evaluating both the degree of decrease in viability and the light scatter changes in all of the strains.ResultsPCR revealed that only one strain exhibits the presence of one resistance gene. Despite this, analyses of strains using FCM evidenced the presence of viable subpopulations after antibiotic treatment. Furthermore, analyses of scatter signals revealed profound changes in the Forward Scatter and Side Scatter of the bacterial populations as a consequence of antibiotic exposure, confirming the viability and membrane potential data. The riverine strains were in general less sensitive to antibiotics than the reference strain (ATCC 25922).Conclusions
Antibiotic resistance is a widespread phenomena. The multiparametric approach based on FCM used in this study, providing results about different aspects (cell viability, membrane potential, light scatter changes), may overcome the limitation of PCR and could represent an adequate method for the evaluation of bacteria responses to antibiotic exposure. © 2014 International Clinical Cytometry Society © 2014 International Clinical Cytometry Society
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.
The antibacterial properties of phenolic compounds and aromatic alcohols (growth inhibition, lethal effect and cytological damage) were investigated. The role of protein and RNA synthesis in the bactericidal action was also determined. All compounds tested demonstrated lethal properties and the ability to alter membranes, especially in Gram-negative bacteria. Efficacious concentrations, however, varied greatly among the compounds. These data corroborate previous findings which suggest that the mechanism of action of these compounds is related to their lipophilia. Moreover, since it was demonstrated that the lethal effect of two aromatic alcohols (phenethyl alcohol and benzyl alcohol) stops when protein synthesis is inhibited, it is likely that both possess specific mechanisms of action.
Cefotaxime has been used extensively in many pediatric centers in the United States for the past 10 or more years. Its main usage has been for the treatment of various serious bacterial infections in pediatric patients, primarily meningitis and sepsis. It has also been used to treat intraabdominal, urinary tract, soft tissue, bone, and joint infections. Although there has been a marked reduction in the incidence of invasive Haemophilus influenzae type b infections following the introduction of effective vaccines, cefotaxime remains very useful against the other common pathogens causing serious infections in pediatric patients. The increasing number of pneumococci resistant to penicillin and third-generation cephalosporins has created a new challenge for the management of serious pneumococcal infections. In many institutions, cephalosporins in general have been overused and abused, resulting in the emergence of resistant organisms and an increasing burden on resources. The judicious use of cefotaxime and other cephalosporins should be emphasized.
The increasing prevalence of ampicillin-resistant Haemophilus influenzae type b has led to the recommendation that ampicillin
and chloramphenicol be given as the initial therapy for suspected bacterial meningitis in infants and children. However, during
the first 2 months of life, H. influenzae type b is a rare cause of meningitis, whereas group B streptococcus is the most
frequently isolated agent. Since ampicillin and chloramphenicol have been shown to be antagonistic for other streptococci,
an in vitro study of their effect on group B streptococci was performed. The effect of ampicillin and chloramphenicol, alone
and in combination, on 18 meningeal isolates was determined for 2 different inocula of group B streptococci, using microtiter
broth dilution and growth kinetic assays. Isoboles, fractional lethal concentration indices, or both indicated antagonism
for all strains. Growth kinetic assays for two representative strains demonstrated inhibition of the early bactericidal activity
of ampicillin by chloramphenicol. These findings of in vitro antagonism suggest that this combination may be contraindicated
for the treatment of infants with group B streptococcal meningitis.
THE DYNAMICS of antimicrobial action are known to some extent for the "older" antibiotics, particularly penicillin. Data are being accumulated at present on the "newer" antibiotics, aureomycin, chloramphenicol and terramycin. Relatively little information, however, is available on the results of simultaneous action of two or more antibiotics. Such basic information is desirable particularly in view of the increasing trend for multiple antibiotic therapy in medical practice.
Two antibiotics acting simultaneously might be additive, synergistic, antagonistic or without any effect on each other. This spectrum of possible combinations has been shown to exist for various sulfonamides¹ and has been suggested for antibiotics.² Synergistic effects have been demonstrated for combinations of penicillin and streptomycin in their action against enterococci in vitro³ and against enterococcic human infections.⁴ In some other infections (e. g., brucellosis) it has also been shown that combinations of antibiotics can achieve results unobtainable with any
The therapy of Proteus mirabilis meningitis with gentamicin alone and in combination with chloramphenicol was studied in a rabbit model. Antibiotics were
administered for 8 hr. Samples of serum and cerebrospinal fluid (CSF) obtained simultaneously were assayed at 2-hr intervals
for antibiotic concentration and counts of bacteria in CSF. The percentage of penetration ([concentration in CSF ÷ concentration
in serum] × 100%) of gentamicin ranged from 14% to 23%, but very large dosages were required to kill bacteria in the CSF.
Although the minimal bactericidal concentration (MBC) of gentamicin was 1 μg/ml, killing in vivo occurred only when concentrations
in CSF were 10–30 times the MBC. The high concentration required for bactericidal activity in vivo may be explained by the
reduced pH of infected CSF (mean pH, 6.98; range, 6.69–7.18). The bactericidal action of gentamicin was abolished by the simultaneous
administration of chloramphenicol. Titers of bacteria in CSF were reduced 2.60 log10 (mean) with gentamicin therapy vs. 0.92 log10 (mean) with the combination (P < 0.01).
Chloramphenicol combined with cefotaxime, moxalactam, cefoperazone, aztreonam, or imipenem was tested in vitro against clinical
isolates of Klebsiella pneumoniae. By time-kill cultures (killing curves), chloramphenicol interfered with activity of all
five beta-lactams. When chloramphenicol was added before the beta-lactams, the action of cefotaxime, moxalactam, or cefoperazone
against all isolates was antagonized at all times tested. The action of aztreonam was antagonized against four of six isolates.
With imipenem, antagonism occurred against half of the isolates at some time during 24 h when chloramphenicol was added simultaneously,
provided that a sufficient inoculum of K. pneumoniae was employed. Generally, less antagonism resulted when chloramphenicol
was added after the cephalosporins. Interference of bactericidal activity of three new cephalosporins by chloramphenicol has
potential clinical relevance to the therapy of gram-negative bacillary meningitis. The lesser antagonism of aztreonam and
imipenem by chloramphenicol is of uncertain clinical relevance but indicates that this in vitro phenomenon may apply to a
wide range of beta-lactam antibiotics.
Because two children with Salmonella osteomyelitis responded differently to a combination of ampicillin and chloramphenicol, we investigated the activity of each antibiotic and the combination against 21 enteric organisms including Salmonella sp. and other Gram-negative bacilli. Ampicillin was bactericidal against all 21 organisms (minimal bactericidal concentration (MBC) range, 0.25 to 16 micrograms/ml). Chloramphenicol was bactericidal against 5 (MBC range, 2 to 16 micrograms/ml) and bacteriostatic against 16 (MBC, greater than or equal to 64 micrograms/ml). Fractional lethal indices indicated that chloramphenicol and ampicillin were antagonistic (fractional lethal concentration, greater than 1.2) against all 16 bacteria for which chloramphenicol was bacteriostatic, and the ampicillin MBC increased from a mean of 2.2 micrograms/ml to 37.2 micrograms/ml. The two antibiotics were synergistic (fractional lethal concentration, less than 0.8) against the five organisms for which chloramphenicol was bactericidal, and the ampicillin MBC was lowered from a mean of 3.0 micrograms/ml to 0.4 micrograms/ml. Our data indicate that the combination of ampicillin and chloramphenicol can be synergistic or antagonistic against Gram-negative enteric bacteria depending on whether chloramphenicol is bactericidal or bacteriostatic against the specific organism.
Antagonists of nucleic acid derivatives. VIII. Synergism in combinations of biochemically related antimetabolites
- G B Elion
- S Singer
- G H Hitchens
- Elion G. B.