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PubMed1977

Interactions of fosfomycin with other antibiotics.

We selected 100 strains of organisms that were isolated in our hospital, which came from pathological products and which had an MIC of fosfomycin of 256 mug/ml or more and belonged to the genera Klebsiella, Pseudomonas, Escherichia coli, Serratia, Enterobacter, Proteus, Acinetobacter, Levinea and Staphylococcus. We have studied the effect of the association of fosfomycin with 15 antibiotics (beta-lactamins, cephalosporins, aminoglycosides, etc.) and 5 chemotherapeutics. The 11 selected strains were studied by the 'chess board' technique in agar. A study was also carried out on the action of fosfomycin on E. coli K12 E711 in the phase of logarithmic growth. The 11 selected strains were studied by the 'chess board' technique in agar. Synergic effect with fosfomycin associated to other antimicrobials was found in 9 strains.

Anti-Bacterial Agents↗
PubMed1979

The sensitivity of Staphylococcus aureus 79 and 80, and Escherichia coli 95 to sodium salicylate, nicotinaldehyde singly, and in combination with nicotinic acid or nicotinamide.

Minimum bactericidal concentrations of salicylate, nicotinaldehyde singly, and in combination with nicotinic acid, or nicotinamide were determined for Staphylococcus aureus 79 and 80, and Escherichia coli 95, at inocula of 10(7)--10(2). The bactericidal dose of salicylate was affected markedly by the inoculum size. The bactericidal dose of nicotinic acid, or nicotinamide was affected only slightly by the size of the inoculum. Escherichia coli 95 was least affected by the inoculum size. Nicotinaldehyde is a far more bactericidal agent than is nicotinic acid, or nicotinamide; its bactericidal dose was approximately a tenth that of nicotinic acid, or nicotinamide. S. aureus 79 and 80 were affected synergistically by the combinations of nicotinic acid, or nicotinamide with salicylate. Nicotinaldehyde reduced the effectiveness of nicotinic acid, at all inoculum sizes, of S. aureus 79, while the reduction of effectiveness of nicotinamide was only found with inocula of 10(7)--10(5). At low inocula, 10(4)--10(2), an additive effect was demonstrated. S. aureus 80 was antagonistically affected, at all inoculum sizes, by the combination of nicotinaldehyde with nicotinamide, while with nicotinic acid a slight synergy was noted. In contrast, Escherichia coli 95 was antagonistically affected, at all inoculum sizes, by combinations of nicotinic acid, nicotinamide with salicylate, or nicotinaldehyde.

Aldehydes↗
PubMed1981

Prevention of emergence of bacterial resistance: no advantage in combining rifampicin and tetracycline over use of tetracycline alone.

Experiments have been performed using rifampicin (RIF) and tetracycline (TET) to establish whether the use of the combination prevents the emergence of bacterial resistance to either drug. Experiments were performed using repeated 4-hour cycles of exposure of large bacterial populations to varying concentrations of antibiotics in order to reproduce in vitro the conditions of treatment of a systemic infection in man. When exposed to both RIF and TET the doubly-sensitive test organism was eliminated from the test cultures in 92 h without emergence of resistance. When the organism was exposed to RIF alone it became massively RIF-resistant in 20 h. The organism was eliminated in 104 h when exposed to TET alone. Under the test conditions there was no significant difference in experimental outcome when RIF was added to TET compared to that when TET alone was used.

Drug Interactions↗
PubMed1983

In vitro activity of cefoxitin, alone and in combination with aminoglycoside or other beta-lactam antibiotics against common gram-negative pathogens.

We examined 160 strains of Enterobacteriaceae and Pseudomonas aeruginosa for susceptibility to cefoxitin, aminoglycosides, and other beta-lactam antibiotics, alone and in combination. The aminoglycosides were the most effective agents tested, but, except for some strains, cefoxitin inhibited all organisms at a 90% minimal inhibitory concentration of 25 micrograms or less per ml. We observed a relatively high incidence of antagonism or nonsynergy when cefoxitin was tested in combination with other agents against 33 gentamicin-susceptible gram-negative bacilli. No synergy was observed when various combinations with cefoxitin were tested against three strains of cephalothin-resistant, carbenicillin-resistant Enterobacteriaceae of varying gentamicin susceptibility.

Aminoglycosides↗
PubMed1984

Enhanced Escherichia coli susceptibility to nitrofurantoin by EDTA and multiple aminoglycoside antibiotics resistance mutation.

Subinhibitory concentrations of ethylenediaminetetraacetic acid (EDTA) increased the susceptibility of Escherichia coli K12 multiple aminoglycoside antibiotics and nitrofurantoin-resistant mutants to aminoglycoside antibiotics (20- to 25-fold) and nitrofurantoin (15-fold). The same concentration of EDTA also increased the susceptibility of high-level nitrofurantoin-resistant mutants to nitrofurantoin. Aminoglycoside-resistant mutants with increased susceptibility to nitrofurantoin (2- to 3-fold) were selected with neomycin from E. coli nitrofurantoin-sensitive and resistant mutants. Decreased permeability of nitrofurantoin is inferred as one of the mechanisms of nitrofurantoin resistance.

Drug Interactions↗
PubMed1986

Effect of 5-fluorouracil, mitoxantrone, methotrexate, and vincristine on the antibacterial activity of ceftriaxone, ceftazidime, cefotiam, piperacillin, and netilmicin.

Using the checkerboard agar dilution technique, antibacterial activity and in vitro interactions of 4 antineoplastic agents and 5 antimicrobial drugs were examined against 56 strains of 7 bacterial species. 5-fluorouracil was found to inhibit all strains of Staphylococcus aureus and of Staphylococcus epidermidis at a concentration of 0.8 micrograms/ml or less. 84% of all gram-negative strains were inhibited synergistically when 5-fluorouracil was combined with beta-lactam antibiotics. Methotrexate and cefotiam were antagonistic in 42% of all combinations, especially when tested against Escherichia coli and Klebsiella pneumoniae.

Anti-Bacterial Agents↗
PubMed1987

Comparative in vitro antimicrobial activity of carumonam (Ro 17-2301) and its influence on the activity of other antibiotics.

The antimicrobial activity of carumonam (Ro 17-2301) was compared with that of 20 antibiotics against 338 clinical isolates. Carumonam did not possess activity against gram-positive cocci, MIC90 of carumonam were less than or equal to 0.5 mg/l for Enterobacteriaceae, except for Citrobacter (less than or equal to 8 mg/l) and less than or equal to 32 mg/l for nonfermenters. It was slightly more active than aztreonam against gentamicin-resistant bacilli (MIC90 less than or equal to 64 vs greater than or equal to 256). Combinations of carumonam with antibiotics with activity against gram-positive microorganisms were indifferent.

Anti-Bacterial Agents↗
PubMed1987

In vitro susceptibility of Mycobacterium avium to a new macrolide (RU-28965).

The in vitro susceptibility of Mycobacterium avium to RU-28965 alone and in combination with rifampin, isoniazid, and sulfametoxipiridazine was studied by the agar dilution method. The synergistic effect of the RU-28965 with rifampin has been demonstrated. At a concentration of 16 micrograms/ml or lower of RU-28965, 100% of M. avium strains were inhibited. If 2 micrograms/ml of rifampin is added the MIC of RU-28965 is lowered to 0.25 microgram/ml.

Anti-Bacterial Agents↗
PubMed1988

In vitro antibacterial activity of imipenem in combination with newer quinolone derivatives.

The antibacterial activity of imipenem combined with norfloxacin, ciprofloxacin, or ofloxacin against 43 gram-positive cocci and 53 aerobic gram-negative rods compared to results obtained with the combination of imipenem with amikacin. Synergistic antibacterial action (defined as FIC index less than or equal to 0.5) was found for 28% of strains with imipenem/amikacin and imipenem/norfloxacin, in 23% with imipenem/ofloxacin, and in 18% with imipenem/ciprofloxacin. Antagonistic activity (FIC index greater than 1.0) was found in 21, 21, 32, and 23% respectively. These rates were not statistically different for gram-positive and gram-negative isolates. Antagonistic activity seemed to occur more frequently with Pseudomonas spp. and enterococci than with staphylococci or Enterobacteriaceae. A tendency for increased rates of antagonism was noted in strains with higher MIC values. Clinically significant and meaningful positive interactions (defined as a decrease of imipenem MICs to below 2.0 micrograms/ml) were found with imipenem/amikacin against several Pseudomonas spp., with imipenem/ofloxacin or ciprofloxacin against Streptococcus faecium and with all combinations against Proteus spp. We conclude that continuous treatment with newer quinolone derivatives for selective decontamination in neutropenic patients receiving imipenem antibacterial therapy for treatment of infection should not be regarded as effective combination therapy.

Amikacin↗
PubMedDate not supplied

Interaction of beta-lactam antibiotics with the penicillin-binding proteins of penicillin-resistant Streptococcus pneumoniae.

The binding of five structurally diverse beta-lactam antibiotics to penicillin-binding proteins (PBPs) of two clinical isolates of Streptococcus pneumoniae resistant to penicillin G was compared with that of a susceptible strain. A common feature of the PBP patterns of the resistant strains was the absence of PBP 1a detected in the susceptible strain. For each beta-lactam antibiotic tested, there appeared to be significant decreases in the affinity for BPB 1b, 2a and 2b of the resistant strains. We attempted to evaluate a quantitative correlation between the antibacterial activity of the drugs for three strains and their affinity for the various PBPs. A close correlation was found between the minimum inhibitory concentrations and the affinity for PBP 2a, but not for any of the other PBPs.

Anti-Bacterial Agents↗
PubMed1997

Does oral isotretinoin prevent Propionibacterium acnes resistance?

Oral and topical antibiotics play a major role in acne therapy. Physicians base treatment choices on personal perceptions of efficacy, cost-effectiveness or risk-benefit ratios and rarely take bacterial resistance into account. Propionibacterium acnes isolates resistant to one or more anti-acne antibiotics have been reported in Europe, the USA, Japan and New Zealand. Therapeutic failure on some but not all antibiotic regimens is an increasing management problem. In Leeds, UK, resistant strains are found in 60% of acne patients and 50% of close contacts. Recommendations for the use of antibiotics in acne therapy to help prevent the emergence of resistance in P. acnes include the implementation of antibiotic usage policies and the encouragement of improved prescribing habits. Strategies to reduce the resistant P. acnes population are necessary. This paper reports preliminary data demonstrating that oral isotretinoin (Roaccutane/Accutane) significantly reduces total numbers of resistant P. acnes on the skin of all patients.

Acne Vulgaris↗
PubMed1976

Interactions between econazole, a broad-spectrum antimicrobic substance, and topically active glucocorticoids.

Econazole is a broad-spectrum antimicrobic substance which acts by permeabilizing the cell membranes. Glucocorticoids by their surface activity may counteract this effect by protecting the cell membranes. In fact, a protective action of glucocorticoids in high concentrations against econazole nitrate could be demonstrated in yeasts, not in staphylococci. The techniques applied were the Warburg assays (resting yeasts, resting and proliferating bacteria). The elicitation of a blanching reaction on human skin by triamcinolone acetonide was not altered in the presence of econazole nitrate. The data collected in this study were discussed in regard to the combined use of antimicrobic drugs and glucocorticoids in topical therapy.

Administration, Topical↗
PubMed1976

Effects of local corticosteroids in skin infections.

Glucocorticoids exert valuable therapeutic activities in skin infections, although their use is limited by the occurrence of undesiderable effects: glucocorticoids depress the local defense mechanisms and in low concentrations, stimulate microbiol metabolism. For these reasons, combined preparations containing an antimicrobiol substance besides the glucocorticoid are recommended. However, interactions between the steroids and the antimicrobiols must be ruled out beforehand, i.e. the unimpaired activity of both steroid and antimicrobial must be assured. Examples of such investigations are reported for the most widely used compounds for topical therapy. The simultaneous use of a glucocorticoid and an antimicrobial is not recommended in only a few instances.

Administration, Topical↗
PubMed1992

Azithromycin: the first azalide antibiotic.

OBJECTIVE: To discuss the chemistry, mechanism of action, spectrum of activity, pharmacokinetics, clinical trials, adverse-effect profile, drug interactions, and dosage guidelines of azithromycin, the first azalide antibiotic. DATA SOURCES: Pertinent literature published between 1988 and the present was identified via a MEDLINE search. Of 77 articles retrieved, 37 have been referenced. STUDY SELECTION: Azithromycin is a new agent, and as such, limited data regarding this drug are available in the literature. We evaluated all pharmacokinetic, microbiologic, and basic science articles pertaining to azithromycin, and reviewed the clinical efficacy trials that we believed were of good quality for each indication for which azithromycin has received approval to date. Comparative clinical trials involving large numbers of patients, clinical outcome assessments, and recommendations for azithromycin use are included. DATA SYNTHESIS: Azithromycin is a macrolide derivative and the first of the 15-membered ring azalide class of antimicrobials. Although its mechanism of action and susceptibility to resistance are similar to those of the macrolide antibiotics, azithromycin's extended spectrum of activity includes gram-positive and gram-negative organisms, as well as atypical pathogens. Azithromycin is stable at gastric pH and has an absolute bioavailability of approximately 37 percent following oral administration. Although its serum concentrations are typically low, the drug concentrates to a high degree in tissue. Azithromycin is cleared primarily by the biliary and fecal routes; its serum half-life is in excess of 60 hours. Several clinical trials have proven that a 5-day course of azithromycin administered once a day is equally efficacious to a 7- to 14-day course of other commonly used oral antimicrobials, administered two to four times a day, for the treatment of upper and lower respiratory tract and skin and skin-structure infections. Urethritis and cervicitis caused by chlamydia are treated with a single 1-g dose. Trials have shown azithromycin's adverse-effect profile to be equal or even superior to that of other agents, with only 0.7 percent of patients discontinuing therapy versus 2.6 percent for comparable drugs. CONCLUSIONS: Azithromycin represents a significant improvement in the treatment of selected community-acquired infections. Although this agent may revolutionize the treatment of sexually transmitted diseases caused by chlamydia, it also should impact the management of respiratory tract and skin and skin-structure infections. Because of its unique pharmacokinetics and excellent adverse-effect profile, patient compliance should be greatly enhanced compared with other commonly used oral antimicrobials. Azithromycin's primary role in the near future will be in the community setting. Although its use in the hospital may be limited, this drug will be a convenient therapeutic option to have on hand in the emergency room and outpatient clinic. Azithromycin may also be used in the future to treat opportunistic infections in immunocompromised patients.

Azithromycin↗
PubMed1996

Performance of the fractional maximal effect method: comparative interaction studies of ciprofloxacin and protein synthesis inhibitors.

The performance of the recently developed Fractional Maximal Effect (FME) method was evaluated along with the conventional checkerboard technique and time-kill method. Ciprofloxacin in combination with tobramycin was tested against Escherichia coli and Pseudomonas aeruginosa and in combination with tetracycline, chloramphenicol, erythromycin against Escherichia coli. Two combinations, amoxicillin-tetracycline (antagonistic) and tobramycin-ticarcillin (synergistic), were included as reference interactions. The FME method unequivocally showed an antagonistic interaction between ciprofloxacin and all the protein synthesis inhibitors (PSIs) tested, while the other two methods yielded variable results. At a total FME (TFME) level of 1, the FME method demonstrated a similar degree of antagonism against ciprofloxacin by tetracycline, chloramphenicol, and erythromycin, and much lower by tobramycin. Internal consistency of the FME operation was demonstrated by the identical conclusions obtained at both TFME levels of 0.5 and 1. The FME method appears to be a practical alternative for resolving the inconsistencies observed in conventional methods of antibiotic combination testing.

Anti-Infective Agents↗
PubMed2004

Tetracycline in combination with sodium dioctylsulfosuccinate show increased antimicrobial activity in resistant microorganisms.

We present evidence that sodium dioctylsulfosuccinate, at non inhibitory concentrations (1000 mg/L), is able to increase the antimicrobial activity of tetracycline in non susceptible bacterial and fungal strains. In culture inhibition tests, pretreatment with sodium dioctylsulfosuccinate caused a 52-fold decrease in the geometric mean MIC to tetracycline in 10 Candida albicans strains (p<0.01), a 165-fold decrease in the geometric mean MIC to tetracycline in 10 E. coli strains (p<0.001) and a significant decrease in the mean MIC of 3 strains of Candida krusei and Candida glabrata. In microbicidal tests, tetracycline in association with sodium dioctylsulfosuccinate killed 10(4) cfu tetracycline-resistant Candida albicans in 15 min and 10(4) CFU resistant E. coli in 3 min (p<0.001). Furthermore, in the N-acetyl-D-glucosamine test to calculate the number of hyphal cells, a combination of tetracycline (50 mg/L) (non inhibitory concentrations) plus sodium dioctylsulfosuccinate (25 mg/L) caused a 50-fold increase in the inhibition of hyphal cells in C. albicans (p<0.001); C. albicans cells treated with tetracycline plus sodium dioctylsolfosuccinate annulled the cell surface hydrophobicity (p<0.001). This increase in antimicrobial activity may be attributed to impairment and alteration of the membrane barrier within the microorganisms and a depletion of the thiol groups (p<0.001) critical to their efficiency.

Anti-Bacterial Agents↗