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Antiviral studies of feline infectious peritonitis virus in vitro.

Sixteen compounds were tested for their ability to inhibit the replication in vitro of feline infectious peritonitis virus (FIPV), a coronavirus that causes a lethal, immunologically mediated illness in domestic and exotic cats. Six of the compounds, when incubated with cells and titrations of the virus, were found to reduce the virus titres by 0.401 to 0.833 log10 (P < 0.05), using the cytopathic effect as endpoint. Further inhibition studies were performed to determine the 50 per cent effective dose (ED50) levels for these six compounds. Selectivity indices (50 per cent cytotoxic dose [CD50]/ED50) provided the following order of antiviral activity: pyrazofuin > 6-azauridine > 3-deazaguanosine > hygromycin B > fusidic acid > dipyridamole. Compounds which had no statistically significant effect on FIPV in the same assay were caffeic acid, carbodine, 3-deazauridine, 5-fluoroorotic acid, 5-fluorouracil, D(+)glucosamine, indomethacin, D-penicillamine, rhodamine and taurine.

Animals↗

Evaluation of bacteria isolated from infected eyes of captive, non-domestic animals.

Bacteria isolated from the eyes of captive species with suspected ocular infections at London Zoo were identified by standard methods. The sensitivity of the organisms to several topical antibiotics was determined by using sensitivity discs, and the minimum inhibitory concentrations of chloramphenicol and fusidic acid were determined. Correlations were evaluated between the results from the antibiotic discs and the minimum inhibitory concentrations and, where possible, between the clinical response to treatment and the results of bacteriological sensitivity tests. Unlike the isolates found in cats and dogs gram-positive cocci accounted for 54 per cent of isolates but almost half of the bacteria isolated were gram-negative organisms.

Animals↗

Suppression by the ColV,I-K94 plasmid of inhibitor sensitivities in ompA mutants of Escherichia coli.

A series of ompA mutants derived from Escherichia coli K12 strains showed increased sensitivity (compared with the ompA+ parents) to aminoglycoside antibiotics and to other cationic agents including polymyxin B. One tested mutant also showed increased sensitivity to nafcillin and fusidic acid, but not to the hydrophilic ampicillin. All these inhibitor sensitivities in the ompA mutants were suppressed by ColV, I-K94 and by certain other ColV plasmids, but not by any of the other tested large plasmids. Suppression correlated with the production of the VmpA protein, but transfer and colicin components were not needed for suppression. Further comparison of the ompA and vmpA genes and their products was made and it indicated that there is little if any homology between the genes, that the synthesis of their products is regulated by quite different mechanisms, and that regions of these gene products exposed at the cell surface show different susceptibility to protease attack after denaturation.

Bacterial Outer Membrane Proteins↗

Antibiotic susceptibility testing (agar disk diffusion and agar dilution) of clinical isolates of Corynebacterium jeikeium.

Thirty-three clinical isolates of Corynebacterium jeikeium were examined for susceptibility to 27 antimicrobial drugs with the agar dilution test. Sheep-blood-supplemented Mueller-Hinton agar performed better than Wilkins-Chalgren agar. Disk susceptibility (Bauer-Kirby) tests were carried out in parallel with 24 of the chemotherapeutic agents. All isolates were susceptible to teicoplanin and vancomycin. All isolates resisted fosfomycin, mupirocin, and trimethoprim-sulfamethoxazole. The isolates varied in susceptibility to ciprofloxacin, doxycycline, fusidic acid, ofloxacin, and tetracycline; most were susceptible to rifampin. Surprisingly few discrepancies between agar dilution and disk diffusion tests were encountered when utilizing NCCLS interpretive criteria currently valid for enterococcal isolates.

Agar↗

Antiseptic efficacy of a low-dosed topical triclosan/chlorhexidine combination therapy in atopic dermatitis.

The topical application of triclosan as an antistaphylogenic antiseptic has proven beneficial in atopic dermatitis. Especially in lipophilic carriers, triclosan is applied in a concentration range between 1 and 5%, usually 2%. However, as a phenol, triclosan is not undisputed and may result in local exacerbation of the disease by eliciting irritative secondary reactions, especially in high concentrations. Chlorhexidine is also an antiseptic which is very effective against Staphylococci and nearly equivalent to triclosan with respect to its antistaphylogenic efficacy. In light of this, the combination of the two active substances in very low concentrations offers a possible option of using the additive effects of the two substances to minimize the risk of side effects. In a uniform W/O emulsion carrier alternatively containing 0.3% triclosan combined with 0.34% chlorhexidine dihydrochloride or 2.0% triclosan, the antibacterial efficacy against Gram-positive skin bacteria could be proven in a preclinical comparison with a reference preparation containing fusidic acid. Subsequently, the pathogen-reducing effect was examined in a clinical study of the influence on clinical severity in patients with atopic dermatitis. Both investigation methods showed that the two test preparations were slightly inferior to the reference preparation, but result in the same degree of pathogen reduction and improvement in the severity of existing atopic dermatitis in direct comparison. The overall results support the conclusion that a combination of triclosan and chlorhexidine in low concentrations as well as the existing antiseptic standard of a 2% triclosan preparation are suitable for pathogen reduction and thus for improving atopic dermatitis.

Adolescent↗

Rifampicin in free combination with other antimicrobial drugs in non-Tb infections. Clinical data on 650 patients (a review).

A review of the published literature has allowed the identification of a number of non-tubercular indications where rifampicin (trade mark Ciba-Geigy: Rimactane) has been successfully used in combination with other chemotherapeutic agents. The cases reviewed with regard to effectiveness sum 562. The most frequently combined drugs were aminoglycosides (mainly gentamicin), cotrimoxazole, colistine, vancomycin and fusidic acid, these two latter in cases due to Staphylococcus spp. The main indications where combined rifampicin treatment led to favourable results were UTI (success rate 64.9%), bone infections (86.9%), staphylococcal endocarditis (85.0%), respiratory tract infections often due to gram-negative rods (97.7%) as well as skin and soft tissue infections (83.3%), and bacterial meningitis (100%). Very favourable results were obtained in a non-life-threatening though epidemiologically important condition, i.e. salmonella carriers, where a 100% conversion rate was reached in an average period of 6 weeks. Special attention may deserve the combined treatment of fungal infections with rifampicin and amphotericin B. Tolerability was evaluated on a total of 650 cases. It appears to be good for daily doses up to 1,200 mg/day, even on long-term treatment; less so for the highest doses used (1,800 or 30 mg/kg a day). The clinical results, which are in good agreement with the results of the in vitro tests, indicate that rifampicin may have an important role in the combined treatment of severe non-mycobacterial infections. Further prospective, whenever possible, comparative studies are warranted for a thorough appraisal of its possible usefulness.

Anti-Infective Agents↗

Activity of eleven antimicrobial agents against methicillin-, methicillin- and rifampin-resistant Staphylococcus aureus.

Activity of eleven antimicrobial agents against methicillin-, methicillin- and rifampin-resistant Staphylococcus aureus was studied using a microtiter broth dilution technique. Coumermycin was the most active agent. Vancomycin, rifampin, fusidic acid and N-formimidoyl-thienamycin showed excellent activity against methicillin-resistant St. aureus (MRSA). Antimicrobial susceptibility pattern was similar for MRSA and methicillin- and rifampin-resistant St. aureus. 8% of MRSA were resistant to trimethoprim and sulfamethoxazole.

Anti-Bacterial Agents↗

Influence of various antimicrobial agents on the chemiluminescence of phagocytosing human granulocytes.

In a standardized experimental model 51 antimicrobial agents were coincubated with polymorphonuclear granulocytes (PNG) of healthy human donors and then screened for a modulation of chemiluminescence (CL) reaction during zymosan phagocytosis. Initial studies with low, therapeutic and high, nontherapeutic concentrations showed CL suppression by amoxicillin, tetracycline, doxycycline, trimethoprim, sulfamethoxazol, clindamycin, fusidic acid, rifampicin, isoniazid and amphotericin B, yet stimulation of CL reaction by ceftriaxone, enoxacin, and norfloxacin. Dose-effect relationships for most of these substances showed a sigmoid-like graph with little influence upon most of the therapeutic range, but markedly increasing suppression (or stimulation) from a certain 'threshold' concentration. For certain substances this curve might indicate a narrowed therapeutic range of antimicrobial chemotherapy due to impairment of phagocytic functions.

Anti-Infective Agents↗

Susceptibility of Clostridium perfringens type A to 23 antimicrobial drugs.

A total of 106 strains of Clostridium perfringens type A, that had been isolated very recently from faecal cultures of healthy adults, were examined for susceptibility to 23 antimicrobial drugs (agar dilution method). All strains were susceptible to ampicillin, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftriaxone, ciprofloxacin, fusidic acid, imipenem, metronidazole, mezlocillin, ofloxacin, penicillin G, piperacillin, teicoplanin, and vancomycin. Teicoplanin and imipenem were the most active, whereas fosfomycin and tetracycline were the least active drugs. Three of the 106 strains revealed multiple drug resistance against clindamycin, erythromycin, josamycin, tetracycline, and, in one instance, against chloramphenicol.

Anti-Bacterial Agents↗

Comparative in vitro bactericidal activity of 24 antimicrobial drugs against Clostridium perfringens.

Twenty-four antimicrobial drugs were examined for rapidity of onset and magnitude of bactericidal activity against selected strains of Clostridium perfringens. Ceftriaxone, imipenem, metronidazole, mezlocillin, penicillin G, piperacillin, and teicoplanin reduced colony counts by at least 3 log10 units within 2-4 h after exposure. Clindamycin, fluoroquinolones, josamycin, and tetracycline caused delayed kill (greater than or equal to 99.9% reduction of viable counts at 4-22 h after exposure). Chloramphenicol and rifampin lacked bactericidal activity against 2 of 4 strains, whereas erythromycin, fusidic acid, and fosfomycin (with added glucose-6-phosphate) were merely inhibitory for all 4 strains. Imipenem and penicillin G were combined with 9 and 12 antimicrobial drugs, respectively. Essentially all drug combinations yielded indifferent effects; only penicillin G plus doxycycline resulted in an antagonistic effect against C. perfringens.

Anti-Bacterial Agents↗

Teicoplanin combined with various antibiotics and human blood against a multiple-drug-resistant strain of Staphylococcus aureus.

Neither teicoplanin nor vancomycin at 2, 1 and 0.5 micrograms/ml consistently killed inocula of representative isolates of a multiple-drug-resistant (MDR) strain of Staphylococcus aureus in the presence of 65% (v/v) of fresh, defibrinated human blood, although both antibiotics sterilized tube contents in Mueller-Hinton broth (MHB). With added human blood, teicoplanin (1 microgram/ml) combined with rifampin (1 microgram/ml) was the most effective in vitro combination, followed by teicoplanin (1 microgram/ml) + amoxicillin (8 micrograms/ml) + clavulanate (3 micrograms/ml), ampicillin (8 micrograms/ml) + sulbactam (8 micrograms/ml), cefamandole (8 micrograms/ml), fosfomycin (4 micrograms/ml + 25 micrograms/ml glucose-6-phosphate), imipenem (8 micrograms/ml), netilmicin (4 micrograms/ml), trimethoprim + sulfamethoxazole (1/19 micrograms/ml) and vancomycin (1 microgram/ml), respectively. Conversely, teicoplanin (1 microgram/ml) combined with fusidic acid (0.5 micrograms/ml) and ofloxacin (4 micrograms/ml), respectively, proved ineffective with 65% (v/v) added human blood. In concurrent control tubes, however, all drug combinations were bactericidally active in MHB against the MDR strain of S. aureus.

Aminoglycosides↗

Enterococcus faecium: in vitro activity of antimicrobial drugs, singly and combined, with and without defibrinated human blood, against multiple-antibiotic-resistant strains.

The minimal inhibitory (MICs) and bactericidal concentrations of 14 antimicrobial drugs were determined against 17 clinical isolates of Enterococcus faecium, including 4 glycopeptide-resistant strains. Both teicoplanin and vancomycin lacked bactericidal activity against all 13 susceptible isolates. Time-kill experiments served to test various antibiotic combinations chiefly against glycopeptide-resistant strains in Mueller-Hinton broth (MHB) and in MHB supplemented with 65% (v/v) fresh defibrinated human blood. Co-trimoxazole, fusidic acid, and novobiocin yielded bacteriostatic effects. Rifampin was bactericidally active against rifampin-susceptible strains (MICs = 0.125 micrograms/ml), but less so against low-level-rifampin-resistant (MICs = 2-8 micrograms/ml) strains in MHB. However, in the presence of human blood, rifampin (2 micrograms/ml) combined with co-trimoxazole (0.25/4.75 micrograms/ml) killed rifampin-susceptible and low-level-rifampin-resistant, but not moderate-level-rifampin-resistant (MICs = 16-32 micrograms/ml) strains of E. faecium. Of two topical drugs examined, mupirocin merely inhibited strains of E. faecium; conversely, taurolidine at 2,000 micrograms/ml was efficacious against all strains examined, although the kinetics of bactericidal activity were retarded somewhat in the presence of 65 vol% human blood.

Anti-Bacterial Agents↗

Comparison of the E test and a proportion dilution method for susceptibility testing of Mycobacterium kansasii.

The newly developed E test was compared with a conventional proportion dilution method for determining the sensitivity of Mycobacterium kansasii to amikacin, streptomycin, fusidic acid, rifampicin, clarithromycin, ciprofloxacin, ofloxacin, and fleroxacin. There was no more than one strain with different rating, except for ciprofloxacin. In this case, the breakpoint concentration had an unfavourable position at the top of the strip, and susceptible isolates in the dilution test were defined resistant in the E test. It is concluded that the E test is suitable for testing slowly growing mycobacteria other than tubercle bacilli, and may replace the more laborious dilution methods, particularly for testing M. kansasii.

Anti-Bacterial Agents↗

Antibiotic susceptibility of alpha- and nonhemolytic streptococci from patients and healthy adults to 24 antimicrobial drugs.

A total of 278 alpha- and nonhemolytic streptococcal isolates (patients, n = 116; healthy adults, n = 162) were examined for susceptibility to 23 and 24 antimicrobial drugs with the Bauer-Kirby agar disk diffusion and the agar dilution method, respectively. Wilkins-Chalgren medium compared favorably with sheep blood Mueller-Hinton agar, the reference medium, for 58 representative streptococcal isolates. In terms of minimal inhibitory concentrations (MICs), all 278 isolates were susceptible to teicoplanin and vancomycin. None of the isolates revealed high-level gentamicin resistance. All isolates were resistant to fusidic acid. Twelve Streptococcus mitis isolates, all from patients, were resistant to penicillin G and variably to other antibiotics. Oxacillin disks failed to predict penicillin G susceptibility. In general, patient isolates were more frequently resistant to beta-lactam antibiotics and fluoroquinolones; conversely, isolates from healthy carriers were slightly more resistant to macrolide antibiotics. Specifically, susceptibility rates were: penicillin G 79.1%, oxacillin 87.8%, ampicillin 66.9%, piperacillin 98.2%, cefoxitin 76.6%, cefuroxime 96.8%, cefotaxime 98.6%, ceftriaxone 98.6%, cefepime 98.6%, impipenem 98.2%, ciprofloxacin 59.7%, ofloxacin 89.2%, doxycycline 65.8%, tetracycline 56.8%, clindamycin 87.8%, erythromycin 59%, clarithromycin 74.9%, chloramphenicol 98.9%, cotrimoxazole 97.9%, rifampin 97.5%, and fosfomycin 2.2%. On the basis of numerous minor discrepancies between disk diffusion and agar dilution test results for certain antibiotics, it is proposed that the current NCCLS inhibition zone (diameter, mm) criteria indicative of intermediate susceptibility of alpha- and nonhemolytic streptococci be changed for the following antimicrobial drugs: ampicillin = I = 22-27 mm; ciprofloxacin = I = 16-18 mm; clindamycin = I = 15-18 mm; doxycycline = I = 17-19 mm; tetracycline = I = 17-19 mm; erythromycin = I = 14-19 mm, and cotrimoxazole = I = 11-13 mm. It is recommended to exclude both cefoxitin and doxycycline (substitute = tetracycline) disks from test batteries for non-group A, B beta-hemolytic and alpha-/nonhemolytic streptococcal isolates.

Adult↗

Fox-Fordyce disease: successful treatment with topical clindamycin in alcoholic propylene glycol solution.

We report a 66-year-old woman with a 3-year history of intensely pruritic follicular papules in the axillar, pubic and inguinal areas. Previous treatment with topical fusidic acid and gentamicin sulfate was ineffective. The clinical and histological examination was consistent with Fox-Fordyce disease. Application of clindamycin in an alcoholic propylene glycol solution led to the clearing of the lesions within 1 month. Nine months later, the treatment was stopped, and no recurrence was observed.

1-Propanol↗

Clinical use of rifampicin in combination for non-mycobacterial infections: a survey of published evidence.

The literature on the clinical use of rifampicin in combination for the treatment of non-mycobacterial diseases is reviewed. From the published evidence, the most promising associations are, for staphylococcal infections, gentamicin, erythromycin, kanamycin and fusidic acid. In the field of Gram-negative infections, Psuedomonas-induced sepsis in particular, data are not so impressive but promising results have been obtained with the associated use of rifampicin and gentamicin or colistin. Some systemic fungal diseases may be successfully treated with rifampicin in combination with amphotericin-B. Although only few reports are available on this subject, the importance of such an application is stressed in view of the severity of these diseases and of the lack of appropriate treatments.

Amphotericin B↗

Melaleuca alternifolia essential oil possesses potent anti-staphylococcal activity extended to strains resistant to antibiotics.

Melaleuca alternifolia Cheel essential oil (TTO) and its major component terpinen-4-ol were examined against a large number of clinical isolates of Staphylococcus aureus to establish their anti-staphylococcal activities. Classic and established procedures were used to study M.I.C., time-kill curves, synergism and mutational frequency. The anti-staphylococcal activity of terpinen-4-ol and TTO were superior to those of antibiotics belonging to the major families (all the tested drugs are for topical use or included in ointments, eye drops or used during surgery); terpinen 4-ol and TTO were active against strains resistant to mupirocin, fusidic acid, vancomycin, methicillin and linezolid. TTO and terpinen-4-ol were bactericidal as revealed by time-kill curves; the frequency of mutational frequency to TTO was < 2.9 x 10 9. The study demonstrates good anti-staphylococcal activity of TTO and terpinen-4-ol against a large number of S.aureus isolates and suggests the possible application of these agents for topical treatment of staphylococcal infections. This is the first extensive study on the anti-staphylococcal activity of TTO. The results suggest that this compound may have application as a topical agent for the control of superficial staphylococcal infections, including activity against organisms resistant to antibiotics which can be used, or are specific, for topical use.

Anti-Bacterial Agents↗

Natural antibiotic susceptibility of Rahnella aquatilis and R. aquatilis-related strains.

A database is described of the natural susceptibilities of 70 Rahnella strains to 71 antibiotics. MIC values were determined by a microdilution procedure and evaluated by a table calculation program. Rahnella aquatilis and R. aquatilis-related strains were naturally resistant to amoxycillin, ticarcillin, fosfomycin and to antibiotics to which other species of Enterobacteriaceae are also intrinsically resistant, i.e. macrolides (except azithromycin), benzylpenicillin, oxacillin, rifampicin, fusidic acid, lincosamides and glycopeptides. Rahnella strains were also naturally resistant or intermediate to cefazolin, cefuroxime and loracarbef. All rahnellae were naturally sensitive or intermediate to doxycycline, minocycline, aminoglycosides, some penicillins and cephalosporins, carbapenems, aztreonam, quinolones, sulfamethoxazole, trimethoprim, cotrimoxazole, chloramphenicol and nitrofurantoin. Bimodal or broad MIC distributions were seen for several antibiotics, e.g. quinolones and cephalosporins. With the exception of quinolones no differences in natural antibiotic susceptibility were seen between reference strains of Rahnella genomovar 1 (n=6) and 2 (n=7). Reference strains of genomovar 1 were pyrase-positive and more susceptible to quinolones than reference strains of genomovar 2, which were pyrase-negative. By discrimination of all rahnellae in the pyrase-positive and pyrase-negative strains the MIC distributions for quinolones became smaller and unimodal. Under the conditions described pyrase might be a parameter to differentiate strains of Rahnella genomovars 1 and 2.

Amoxicillin↗