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 4,089 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study investigated the antibacterial activity of human pleural fluid (HPF) and its interaction with gentamicin (GM), meropenem (MRPM), ciprofloxacin (CPFX) and clarithromycin (CLTM) against Escherichia coli K-12, Proteus rettgeri (Sanelli) and Staphylococcus aureus. Minimal inhibitory concentrations or volumes, expressed as MIC or volume percentage (MIV, V/V%), were measured using a micro-dilution technique in microtiter plates. The antimicrobial activity of HPF combinations with antimicrobial drugs was evaluated by the chequerboard method calculating the fractional inhibitory concentration index (FIC) values. HPF MIVs (%) were: 37.54; 19.85; 1.74 for E. coli, P. rettgeri and S. aureus, respectively. FIC values indicated a synergistic effect with GM, MRPM and CPFX against E. coli and P. rettgeri and an additive effect for the combination HPF plus CLTM or indifference with HPF plus GM and CPFX against S. aureus. The presence of antibodies, complement factors, lysozyme, alpha-defensins and enzymes could explain the antimicrobial activity of HPF and its synergistic effect with certain antibiotics.
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PMID:Antibacterial activity of human pleural fluid: alone and in combination with antibiotics. 991 8

Linezolid was tested against 70 strains of Helicobacter pylori by the agar dilution method. The MIC range and MICs at which 50 and 90% of strains were inhibited were 8 to 64, 16, and 32 microgram/ml, respectively. With minimum and maximum fractional inhibitory concentration summation values of 0.31 and 2.50, respectively, the combination of linezolid with amoxicillin, clarithromycin, or metronidazole showed either partial synergy or indifference for the majority of strains.
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PMID:In vitro activities of linezolid alone and in combination with amoxicillin, clarithromycin, and metronidazole against Helicobacter pylori. 1085 65

The interaction of amphotericin B (AmB) and azole antifungal agents in the treatment of fungal infections is still a controversial issue. A checkerboard titration broth microdilution-based method that adhered to the recommendations of the National Committee for Clinical Laboratory Standards was applied to study the in vitro interactions of AmB with fluconazole (FLC), itraconazole (ITC), and the new investigational triazole SCH 56592 (SCH) against 15 clinical isolates of Cryptococcus neoformans. Synergy, defined as a fractional inhibitory concentration (FIC) index of < or =0.50, was observed for 7% of the isolates in studies of the interactions of both FLC-AmB and ITC-AmB and for 33% of the isolates in studies of the SCH-AmB interactions; additivism (FICs, >0.50 to 1.0) was observed for 67, 73, and 53% of the isolates in studies of the FLC-AmB, ITC-AmB, and SCH-AmB interactions, respectively; indifference (FICs, >1.0 to < or =2.0) was observed for 26, 20, and 14% of the isolates in studies of the FLC-AmB, ITC-AmB, and SCH-AmB interactions, respectively. Antagonism (FIC >2.0) was not observed. When synergy was not achieved, there was still a decrease, although not as dramatic, in the MIC of one or both drugs when they were used in combination. To investigate the effects of FLC-AmB combination therapy in vivo, we established an experimental model of systemic cryptococcosis in BALB/c mice by intravenous injection of cells of C. neoformans 2337, a clinical isolate belonging to serotype D against which the combination of FLC and AmB yielded an additive interaction in vitro. Both survival and tissue burden studies showed that combination therapy was more effective than FLC alone and that combination therapy was at least as effective as AmB given as a single drug. On the other hand, when cells of C. neoformans 2337 were grown in FLC-containing medium, a pronounced increase in resistance to subsequent exposures to AmB was observed. In particular, killing experiments conducted with nonreplicating cells showed that preexposure to FLC abolished the fungicidal activity of the polyene. However, this apparent antagonism was not observed in vivo. Rather, when the two drugs were used sequentially for the treatment of systemic murine cryptococcosis, a reciprocal potentiation was often observed. Our study shows that (i) the combination of triazoles and AmB is significantly more active than either drug alone against C. neoformans in vitro and (ii) the concomitant or sequential use of FLC and AmB for the treatment of systemic murine cryptococcosis results in a positive interaction.
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PMID:Interactions between triazoles and amphotericin B against Cryptococcus neoformans. 1095 92

The influence of non-quinolone antimicrobial agents on the antibacterial activities of gatifloxacin and ciprofloxacin was determined using chequerboard, fractional inhibitory concentration, (FIC) and time-kill analysis methods. In the chequerboard method, the quinolones were tested in combination with ten antimicrobial agents (macrolides, aminoglycosides, beta-lactams, vancomycin, rifampicin and chloramphenicol) against five bacterial strains (one strain each of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis and Streptococcus pneumoniae). In no incidence was antagonism (FIC > or = 4) or synergy (FIC < or = 0.5) observed; all dual drug combinations involving gatifloxacin or ciprofloxacin showed additivity/indifference (FIC > 0.5, < 4). By time-kill analysis, the strains were tested at a quinolone concentration equal to 8 x MIC in combination with a second antibiotic at 0.5xits MIC. These combinations killed non-enterococcal strains at rates similar to those with quinolones alone. However, rifampicin and chloramphenicol were often antagonistic (100-fold lesser killing) to the lethal action of gatifloxacin and ciprofloxacin against E. faecalis. These findings indicate that, with the exception of E. faecalis, the antibacterial activities of quinolones are generally additive/indifferent to those of other antimicrobial agents.
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PMID:Activity of gatifloxacin and ciprofloxacin in combination with other antimicrobial agents. 1116 13

There are no data regarding the activity of clarithromycin's active metabolite, 14-hydroxy clarithromycin, against penicillin-intermediate, penicillin-resistant or erythromycin-resistant Streptococcus pneumoniae. Agar dilution MICs were determined for clarithromycin, 14-hydroxy clarithromycin (henceforth called 'metabolite'), azithromycin, erythromycin and clarithromycin/metabolite (2:1 and 1:1 ratio) against 24 penicillin-intermediate and 14 penicillin-resistant strains, including 13 erythromycin-resistant clinical strains and one ATCC strain of S. pneumoniae. The interaction between clarithromycin and its metabolite was determined using an agar chequerboard assay against all isolates, and time-kill tests were performed against five penicillin-intermediate (macrolide-susceptible) and five penicillin-resistant (two macrolide-resistant) strains of S. pneumoniae using all antibiotics alone at simulated peak serum concentrations, and clarithromycin/metabolite in a 2:1 ratio (physiological). MICs were as follows: clarithromycin, 0.008-->64 mg/L; metabolite, 0.015-->64 mg/L; erythromycin, 0.015-->64 mg/L; azithromycin, 0.125-->64 mg/L; clarithromycin/metabolite (1:1 and 2:1 combinations), 0.001-->64 mg/L. The MIC of the clarithromycin/metabolite combination was one or more tube dilution lower than the MIC of clarithromycin in 28 of the isolates tested. In chequerboard testing, 13 strains (seven erythromycin susceptible and six erythromycin resistant) demonstrated synergy, 18 additivity and seven indifference. In time-kill testing, bacterial eradication below detection limits occurred with clarithromycin and metabolite in seven of 10 organisms. The combination of parent and metabolite was more rapidly bactericidal than clarithromycin alone in six of the seven isolates (P = 0.026). The metabolite has potent activity against S. pneumoniae and enhances the activity of the parent compound against this organism. The metabolite's activity must be considered in evaluating clarithromycin in vitro to avoid underestimation of clarithromycin's activity against the pneumococcus.
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PMID:The activity of 14-hydroxy clarithromycin, alone and in combination with clarithromycin, against penicillin- and erythromycin-resistant Streptococcus pneumoniae. 1132 68

Caspofungin and itraconazole were studied alone and in combination against 31 clinical isolates of Aspergillus spp. according to NCCLS M38-P guidelines. MICs and microscopic minimal effective concentrations (MECs) were recorded, and synergy was calculated by using both end points. Synergy or synergy to additivity was found in 30 of 31 isolates by using MIC end points. With MEC end points no synergy was found and indifference was detected in 26 of 31 strains.
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PMID:In vitro synergy of caspofungin and itraconazole against Aspergillus spp.: MIC versus minimal effective concentration end points. 1265 81

Aztreonam has been commonly used in various combinations to enhance antimicrobial spectrum of co-drugs and produce potential synergistic activity. Although well studied in vitro over 10 years ago, aztreonam combination testing has been poorly documented with newer or commonly used agents against contemporary isolates. All MIC tests (alone or in combination) used in this experiment were reference broth microdilution methods in checkerboard tray designs. Aztreonam was combined with ciprofloxacin, gatifloxacin, levofloxacin, cefepime, ceftazidime and imipenem at clinically relevant concentrations. Interaction categories were defined by established criteria. Forty strains each of Pseudomonas aeruginosa and Enterobacteriaceae (12 species; aztreonam MIC, 1-16 microg/ml) were tested for each antimicrobial combination (480 total determinations). No antagonism or indeterminate interactions were identified. The overall rates of synergy or partial synergy for aztreonam with fluoroquinolone combinations was 63.4% versus P. aeruginosa, greatest for aztreonam with gatifloxacin (67.5%). Interaction categories varied greatly among aztreonam with beta-lactam combinations. Aztreonam with ceftazidime or cefepime versus P. aeruginosa had 75.0 - 85.0% partial or complete synergy rates, but aztreonam with imipenem showed dominant indifference (65.0%). In contrast, aztreonam with imipenem was more likely to exhibit synergy (32.5%) when tested against Enterobacteriaceae. Aztreonam, often used as an aminoglycoside substitute in antimicrobial combinations, continues to demonstrate enhanced, but variable drug activity interactions for contemporary antimicrobial combinations when tested against recent (2002) clinical isolates.
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PMID:Contemporary in vitro synergy rates for aztreonam combined with newer fluoroquinolones and beta-lactams tested against gram-negative bacilli. 1459 74

BAL9141 has been reported to have inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA), many enterococci, and streptococci with various resistant patterns. BAL9141 potency was assessed by time-kill curves alone or with subinhibitory concentrations of gentamicin (MIC/4). BAL9141 exhibited bactericidal activity alone against all the streptococci and staphylococci. Among ampicillin-susceptible enterococci, BAL9141 was bactericidal against some strains, but no BAL9141 inhibition was observed of ampicillin-resistant Enterococcus faecium. The activity of BAL9141 with gentamicin was slightly enhanced (not synergy) or indifferent against staphylococci. BAL9141 demonstrated bactericidal action alone against Enterococcus faecalis and some E. faecium strains (-4.8 to -6.0 log10 CFU/mL), but static effects were also noted. Drug interactions with gentamicin showed early synergy (4-8 h) for all enterococci, and indifference or synergy at 24 h (no antagonism). BAL9141 (< or = 8 mg/L) showed promising bactericidal activity alone and synergy with gentamicin against some of the vancomycin-resistant enterococci tested.
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PMID:Bactericidal activity and synergy studies of BAL9141, a novel pyrrolidinone-3-ylidenemethyl cephem, tested against streptococci, enterococci and methicillin-resistant staphylococci. 1461 30

Caspofungin (CAS) inhibits fungal cell wall synthesis. Sulfamethoxazole (SMX) inhibits folate biosynthesis and is active in vitro against Aspergillus spp. We studied the activities of the combination of CAS and SMX against 31 Aspergillus isolates and compared them with that of SMX combined with amphotericin B (AMB) or itraconazole (ITC). MICs and minimal effective concentrations (MECs) were determined by the NCCLS broth microdilution method. With MIC endpoints, the combination of SMX and CAS showed synergy or synergy to additivity against 29 of 31 isolates. With MEC endpoints, synergy to additivity was found against 12 of 31 isolates and indifference was displayed against the rest of them. SMX in combination with AMB or ITC was not truly synergistic, while synergy to additivity was found for SMX-AMB and SMX-ITC against 17 of 31 and 3 of 12 isolates, respectively. No antagonism was found with any of the drug combinations. Further analysis of the synergy of CAS and SMX was performed by detailed measurement of hyphal length by microscopy and time-dependent 2,3-bis(2-methoxy-4-nitro-5-[(sulfenylamino)carbonyl]-2H-tetrazolium hydroxide (XTT)-based hyphal damage experiments. With MEC endpoints, the combination of CAS and SMX was characterized by a greater than 50% decrease in hyphal length compared to the hyphal lengths achieved with double the concentration of each drug alone. The XTT-based hyphal damage studies showed a statistically significant (P < 0.05) reduction in viability with CAS and SMX in combination compared to the viabilities achieved with double the concentration of each drug alone. These findings support the synergy results found by using MIC endpoints and suggest that visual MEC measurements may not be sufficient to identify the synergistic interactions seen by more sensitive, quantitative methods. Animal models are required to validate the significance of the synergy of CAS and SMX against Aspergillus spp. observed in vitro.
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PMID:In vitro activity of caspofungin combined with sulfamethoxazole against clinical isolates of Aspergillus spp. 1532 85

Indifference or moderate antagonism of linezolid combined with other antibiotics in vitro and in vivo have mainly been reported in the literature. We have assessed the in vitro activities of linezolid, alone or in combination with imipenem, against methicillin-resistant Staphylococcus aureus (MRSA) strains using the dynamic checkerboard and time-kill curve methods. Linezolid and low concentrations of imipenem had a synergistic effect, leading us to evaluate the in vivo antibacterial activity of the combination using the rabbit endocarditis experimental model. Two MRSA strains were used for in vivo experiments: one was a heterogeneous glycopeptide-intermediate clinical S. aureus strain isolated from blood cultures, and the other was the S. aureus COL reference strain. Animals infected with one of two MRSA strains were randomly assigned to one of the following treatments: no treatment (controls), linezolid (simulating a dose in humans of 10 mg/kg of body weight every 12 h), a constant intravenous infusion of imipenem (which allowed the steady-state concentration of about 1/32 the MIC of imipenem for each strain to be reached in serum), or the combination of both treatments. Linezolid and imipenem as monotherapies exhibited no bactericidal activity against either strain. The combination of linezolid plus imipenem showed in vivo bactericidal activity that corresponded to a decrease of at least 4.5 log CFU/g of vegetation compared to the counts for the controls. In conclusion, the combination exhibited synergistic and bactericidal activities against two MRSA strains after 5 days of treatment. The combination of linezolid plus imipenem appears to be promising for the treatment of severe MRSA infections and merits further investigations to explore the mechanism underlying the synergy between the two drugs.
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PMID:In vitro and in vivo synergistic activities of linezolid combined with subinhibitory concentrations of imipenem against methicillin-resistant Staphylococcus aureus. 1561 74


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