In Vitro Activity of Cefpirome (HR 810) against Enterococci and Staphylococci

Summary

The inhibitory activity of cefpirome (HR 810), a new cephalosporin derivative for parenteral use, was tested by agar dilution methods against Enterococcus faecatis (100 strains), Staphylococcus aureus (40 strains) and coagulase-negative staphylococcal species (60 strains) in comparison with other beta-lac ta m antibiotics.

For E. faecalls, the cefpirome minimum inhibitory concentration (MIC) range was 2-128 μg/ml, with an MIC,, of 8 μg/ml, and an MIC₉₀, of 64 μg/ml. The optimal bactericidal activity against strains with MICs of ≤ 8 μg/ml occurred at 2-4 times the MIC, and the reduction in the initial inoculum was 99.9-99.7% after 24 h incubation at these concentrations.

Mec gene-negative staphylococci (both S. aureus and coagulase- negative species) had cefpirome MICs of 0.25-2 μg/ml (MIC₅₀ 0.5 μg/ml, MIC₉₀ 1 μg/ml). Mec gene-positive strains had MICs of 0.5-128 μg/ml (MIC₅₀ 2 μg/ml, MIC₉₀ 32 μg/ml). Strains with borderline resistance to oxacillin which did not harbor the mec gene and which were susceptible to cefpirome maintained their susceptibility even when high-density inocula were used and after several passages in media containing the antibiotic.

These studies present some potential advantages of cefpirome over other cephalosporins in the inhibitory activity against Gram-positive cocci.     

Antibacterial Activity of the Sulbactam-Ampicillin Combination

Summary

The in vitro antibacterial activity of ampicillin combined with sulbactam 2:1 was evaluated on 257 aerobic Gram-positive and Gram-negative bacteria, and on 174 anaerobic bacteria from isolated hospital strains by evaluating the minimum inhibitory concentration (MIC).

The results obtained show a synergic effect which was able to significantly decrease the MIC₉₀ of the tested betalactamase producing bacteria. Among the Gram-positive aerobic strains, we underline the efficacy of sulbactam/ampicillin on resistant Staphylococci, including those methicillin-resistant.

The activity on the Gram-negative strains was particularly evident against enterobacteria and Haemophilus.

The combination of sulbactam and ampicillin provides increased activity against anaerobic strains, including Bacter-oides fragilis.     

In- Vitro Susceptibility of Clinical Isolates of Pseudomonas aeruginosa to β-Lactam and Aminoglycoside Antibiotics

Summary

The in-vitro susceptibilities of 198 isolates of Pseudomonas aeruginosa from clinical human specimens were determined by an agar dilution technique against (β-lactams and aminoglycosides. These isolates were susceptible to imipenem, aztreonam and ceftazidime with the minimum inhibitory concentration (MIC) for 90% of the strains tested being 8, 16 and 8 μg/ml, respectively. Aminoglycosides, except amikacin, had low activity (MIC90 > 128 μg/ml).     

In Vitro Activity of Lomefloxacin (SC-47111) Against Enterobacteriaceae,Enterococci and Staphylococci

Summary

The activity of lomefloxacin, a new difluorinated quinolone, was tested against 190 Enterobacteriaceae strains (belonging to 23 different species), 70 enterococci and 70 staphylococci. As regards Enterobacteriaceae, the activity of lomefloxacin was the same as that of norfloxacin in 9 out of the 23 species tested, and only slightly lower in further 8 species. Minimum inhibitory concentrations (MIC) values for 90% of strains were 0.5 μg/ml in 2 species, 0.25 μg/ml in 6, 0.125 μg/ml in 4, and lower than 0.125 μg/ml in 8. Slightly higher values were obtained for Serratia marcescens (2 μg/ml), whilst, as already reported for the other new quinolones, the susceptibility of the Providencia genus was very poor, with MIC values up to 128 μg/ml for the vast majority of strains. Lomefloxacin proved bactericidal at the MIC in all the Enterobacteriaceae strains tested but 20. In the latter strains, however, bactericidal activity could be appreciated at values slightly exceeding MIC. As regards enterococci, the MIC for 90% of strains was 32 μg/ml. Minimum bactericidal concentration (MBC) was the same as the MIC for 78% of the strains tested and was only twofold higher in all the others. The new drug was also active against staphylococci having an MIC50 and MIC₉₀ of 0.5 and 2 μg/ml, respectively. It was bactericidal at the MIC for 62% of the strains and at twofold the MIC for all the others.     

The In Vitro Activity of Trospectomycin against Anaerobic Bacteria

Abstract

The authors evaluated the activity of trospectomycin, a new aminocyclitol which is characterized by good antibacterial and broad spectrum activity, in comparison with clindamycin and ampicillin on a sample of recent isolates: Bacteroides fragilis (15 strains), Bacteroides urealyticus (5 strains), Bacteroides vulgatus (5 strains), Bacteroides spp. (15 strains), Prevotella melaninogenica (6 strains), Porphyromonas asaccha-rolytica (7 strains), Mobiluncus spp. (3 strains), Peptococcus niger (3 strains), Peptococcus variabilis (9 strains), Peptococcus spp (30 strains), Peptostreptococcus anaerobius (5 strains), Peptostreptococcus asaccharolyticus (3 strains), Peptostreptococcus spp. (25 strains) and Propioni-bacterium spp. (7 strains). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined for all strains by microtiter serial dilutions in Wilkins-Chalgren broth in an anaerobic chamber in an atmosphere of 10% H₂, 10% CO₂, 80% N₂. All the drugs tested exert their activity against Gram-positive and Gram-negative anaerobic isolates. In particular, trospectomycin is quite active against Gram-positive cocci (MIC 90 = 4 - 8 mg/l), Gram-negative rods (MIC 90 = 8 - 16 mg/l), Gram-positive rods (MIC 90 = 4 mg/l) and Mobiluncus spp. (MIC 90 = 0.5 mg/l).     

Interference on Helicobacter pylori Growth and Adhesion by Omeprazole and Other Drugs

Abstract

Helicobacter pylori is the causative agent of gastritis and a co-agent in other gastroduodenal diseases. Gastroduodenal ulcer and MALT-lymphoma in particular, regress when patients are administered antimicrobial agents to eradicate infection. Sometimes eradication is not definitive and is difficult to check. The aim of our study was to test the antimicrobial activity of omeprazole on H. pylori in comparison with ampicillin and other anti-H₂ drugs (ranitidine and famotidine), and to evaluate their interference with bacterial adhesion of H. pylori. We also compared results of the agar dilution antibacterial sensitivity test on H. pylori to those obtained using a bacteria adherence to cell monolayers model, to see if drug activity was different against adhered bacteria. We evaluated omeprazole and ampicillin MIC90s (minimum inhibitory concentrations) against 20 H. pylori isolates by traditional agar dilution method and by exposing previously adhered bacteria to an Hep-2 monolayer to different drug concentrations. The activity against bacteria adhered to cell lines was evaluated by counting viable adhered bacteria after 1, 6, 12 hours of contact with drug. Interference with adherence to Hep-2 cells was also tested. Omeprazole and ampicillin MICs were comparable to other findings (omeprazole MIC90 was 12.5 μg/ml and ampicillin MIC90 was 0.016 μg/ml), while higher concentrations were necessary (4 × MIC90) against adhered bacteria. These findings suggest that MICs evaluated with traditional assays can have different predictivity than tests on adhered H. pylori.     

Determination of the Susceptibility In Vitro of 54 Isolates of Mycobacterium fortuitum against Three Fluoroquinolones Using Two Methods

Abstract

The In Vitro susceptibility to ofloxacin, norfloxacin and ciprofloxacin or 54 Mycobacterium fortuitum isolates originating from clinical samples (7) of patients attending the Hospital Universitario de Canarias and Hospital del Tórax, and from environmental (47) sources, were determined. For this, two methods were used: dilution in agar with Middlebrook 7H10 Agar as a base medium culture, and broth microdilution, with Mueller-Hinton Broth without supplement.

The different isolates under study revealed a uniform susceptibility by both methods against ciprofloxacin.

100% inhibition was obtained from a Minimum Inhibitory Concentration (MIC) of 0.25 μg/ml, and 2 μg/ml of ciprofloxacin, for broth microdilution and dilution in agar, respectively.

For ofloxacin and norfloxacin, all the isolates were inhibited at an MIC of 0.5 μ/ml, by the broth microdilution method, which contrasted sharply with an MIC of 32 μ/ml, in the case of dilution in agar.

In this study, we have observed the existence of differences in the In Vitro susceptibility of the isolates of M. fortuitum against the three fluoroquinolones assayed, mainly for ofloxacin and norfloxacin, by both methods. We, therefore, consider it necessary to establish a standardized, reproducible assay method, for the study of sensitivity to atypical mycobacteria.     

Ofloxacin: In Vitro Activity Against Recently Isolated Gram-Negative Bacterial Strains

Summary

The activity of ofloxacin was determined against 117 Enter obacteriaceae, 13 Acinetobacter var. anitratus, 124 Pseudomonas aeruginosa in comparison with other antibiotics. Its activity was very high: against Enterobacteriaceae the minimum inhibitory concentration (MIC)₅₀ was 0.125 μg/ml, the MIC₉₀ lμg/ml, and the geometric mean (GM) was 0.4 μg/ml; against Acinetobacter var. anitratus the MIC₅₀ 1 μg/ml, MIC₉₀ 4 μg/ml, GM 1.7 μg/ml. Unlike other authors we found that the activity of ofloxacin was influenced by the selection of P. aeruginosa resistant to carbenicillin and gentamicin.     

Comparative Evaluation of the In Vitro Antimycobacterial Activities of Six Aminoglycoside Antibiotics Using an Agar Dilution Method

Abstract

Given the increasing prevalence of mycobacterial resistance to aminoglycoside antibiotics, we examined the susceptibility of 76 clinical isolates of mycobacteria to arbekacin, amikacin, gentamicin, kanamycin, tobramycin and streptomycin using an agar dilution method. Only arbekacin and amikacin showed excellent therapeutic potential (minimum inhibitory concentrationis (MICs) ≤0.25-4 μg/ml) against 30 isolates of rapidly growing mycobacteria, including Mycobacterium fortuitum M. chelonae and a related organismNocardia asteroides. The MIC₉₀ of tobramycin against 23 isolates of M. avium complex was 8 μg/ml, while that of the other 5 aminoglycosides ranged from 64-256 μg/ml. Of the 23 M. tuberculosis isolates tested, 5 showed aminoglycoside resistance (MICs 128 to ≥1,024 μg/ml), while the others were variably susceptible (MICs ≤0.25-32 μg/ml) to all 6 aminoglycosides. The chemotherapeutic potential of arbekacin, amikacin and streptomycin as treatment of tuberculosis was apparent; however, proper patient management would be required to control against the emergence of the drug-resistant strains during prolonged treatment.     

In vitro activities of antimicrobial cationic peptides; melittin and nisin,alone or in combination with antibiotics against Gram-positive bacteria

Abstract

The in vitro activities of two antimicrobial cationic peptides, melittin and nisin alone and in combination with frequently used antibiotics (daptomycin, vancomycin, linezolid, ampicillin, and erythromycin), were assessed against clinical isolates of methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus and Enterococcus faecalis. Using the broth microdilution method, minimum inhibitory concentration (MIC) ranges of melittin and nisin against all strains were 2–8 μg/ml and 2–32 μg/ml respectively. In combination studies performed with the microdilution checkerboard method using a fractional inhibitory concentration index of ?0·5 as borderline, synergistic interactions occurred more frequently with nisin–ampicillin combination against MSSA and nisin–daptomycin combination against E. faecalis strains. The results of the time-killing curve analysis demonstrated that the concentration dependent rapid bactericidal activity of nisin, and that synergism or early synergism was detected in most strains when nisin or melittin was used in combination with antibiotics even at concentrations of 0·5×MIC.     

Bactericidal Kinetics and Postantibiotic Effect of Sparfloxacin against Selected Species of Respiratory Pathogens

Abstract

We determined the bactericidal kinetics and postantibiotic effect (PAE) of sparfloxacin against Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, Klebsiella pneumoniae, Streptococcus pneu-moniae, and Staphylococcus aureus. Time-kill studies were performed by using 1 × and 4 × the minimum inhibitory concentrations (MICs) of sparfloxacin, ciprofloxacin, co-trimoxazole, amoxicillin/clavulanic acid and erythromycin (inoculum 10⁵ and 10⁷ CFU/ml). The PAE was induced by exposing the strains to 1×MIC and 4×MIC of sparfloxacin and ciprofloxacin for 1 h. Sparfloxacin was the most bactericidal of all the antibiotics tested, being active against Gram-positive and Gram-negative isolates with a 99.9% reduction within 3 to 6 h of exposure, depending upon strain, inoculum and concentration. The PAE of sparfloxacin against all species tested ranged from 1.1 to 2.6 hours; the most notable PAE occurring with M. catarrhalis.     

In Vitro Antifungal Activity of Sertaconazole Against 309 Dermatophyte Clinical Isolates

Abstract

Three hundred and nine strains belonging to 11 species of dermatophyte moulds were tested against sertaconazole following mainly the National Committee for Clinical Laboratory Standards (M38-P) for filamentous fungi. However, several important factors such as the temperature (28°C vs 35°C) and time of incubation (4-10 d vs 21-74 h), have been modified. Sertaconazole was active against all the clinically important dermatophyte moulds involved in human infections tested. Overall geometric mean MIC of sertaconazole was 0.21 μg/ml with a MIC range of 0.01-8 μg/ml. MIC₅₀ and MIC₉₀ were respectively of 0.25 and 1 μg/ml. Sertaconazole was very active against Epidermophyton floccosum, Trichophyton rubrum, Trichophyton tonsurans and Microsporum canis (geometric means 0.08, 0.13, 0.13 and 0.19 μg/ml respectively). Microsporum audouinii had the lowest susceptibility in the study (geometric mean 0.59 μg/ml). Considering MIC₅₀ and MIC₉₀ these differences were significantly in favor of the activity of sertaconazole against E. floccosum (0.06 and 0.5 μg/ml respectively).     

Comparative In- Vitro Activity of Fourteen Antibiotics Against Clinical Isolates of Enterococci

Summary

The in-vitto antibacterial activities of fourteen antimicrobial agents, including ampicillin, amikacin, Augmentin, ceftazidime, cefotaxime, ceftriaxone, ciprofloxacin, erythromycin, gentamicin, penicillin G, piperacillin, rifampicin, streptomycin and vancomycin, were compared against 195 enterococcal strains isolated from clinical specimens received at the King Abdulaziz University Hospital in Saudi Arabia. The antibacterial susceptibility was determined by the minimal inhibitory concentration (MIC) using an agar dilution method. Ampicillin, Augmentin and vancomycin exhibited the greatest activity, inhibiting 90% of the tested strains (MIC90) at 2 μg/ml, followed by penicillin G and piperacillin with MIC90 of 4 μg/ml. Erythromycin, third generation cephalosporins, aminoglycosides and rifampicin, on the other hand, had poor activity against enterococci with MIC90s well above the obtainable serum concentrations. The clinical implications of resistance to aminoglycosides and the alternative antimicrobial therapy in serious entrococcal infections are discussed in the text.     

In Vitro and In Vivo Activity of Miltefosine Against Penicillin-Sensitive and -Resistant Streptococcus pneumoniae Strains

Abstract

The in vitro and in vivo activity of miltefosine against penicillin-sensitive and penicillin-resistant pneumococcal strains was studied. The minimum inhibitory concentrations (MICs) of miltefosine were determined in cation-adjusted Mueller Hinton plus 2% lysed horse blood (CAMHB) and in Todd-Hewitt (TH) broth. The respective MICs were higher using CAMHB (128 and 64 mg/L) than using TH broth (4 and 8 mg/L). The In Vivo activity was studied in a murine peritonitis-sepsis model. Miltefosine was orally administered at doses of 15 and 30 mg/kg/day after, at the time of, and before bacterial challenge for 3-5 days. All control and 16 out of the 17 (94.1%) miltefosine-treated animals that were inoculated with the penicillin-sensitive strain died. No survival was observed among control and miltefosine-treated animals inoculated with the penicillin-resistant pneumococcal strain. The In Vivo unresponsiveness of miltefosine in this sepsis model could be attributed to some inhibitory effect of blood, inadequate pharmacokinetics and/or the extracellular localization of the pneumococcus.     

In Vitro Activity of Clarithromycin Against Penicillin-Susceptible and Penicillin-Resistant Strains of Streptococcus pneumoniae in a Pharmacodynamic Simulation Model

Abstract

Clarithromycin has shown enhanced activity against Streptococcus pneumoniae, but increased resistance to macrolides has been observed in recent years. Our aim was to investigate its activity against strains of S. pneumoniae with variable susceptibility to this antibiotic and to penicillin. We determined killing curves using the Centriprep-10 pharmacodynamic simulation model, which permits using varying antibiotic concentrations to mimic a pharmacoki-netic human profile in serum (corresponding to an oral dose of 500 mg). Four strains of S. pneumoniae were tested. In susceptible strains, clarithromycin showed bactericidal activity (reductions of up to 2.97 log₁₀ cfu/ml of the initial inoculum). In resistant strains, clarithromycin showed a bacteriostatic effect (<1 log₁₀ cfu/ml reduction). Penicillin-susceptible strains showed higher reductions than penicillin-resistant strains. This effect is important owing to the high minimum inhibitory concentration (MIC) of one of the resistant strains (32 μg/ml). More studies are needed to explain this bacteriostatic activity.     

In Vitro Susceptibility of Trichosporon beigelii to Antifungal Agents

Abstract

The minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) of amphotericin B, flucytosine, miconazole, fluconazole and itraconazole against 21 isolates of Trichosporon beigelii in RPMI-1640 medium were determined using National Committee for Clinical Laboratory Standards (NCCLS) methodology in microdilution method. Most isolates were sensitive to miconazole (MIC₉₀ 0.78 μ/ml), fluconazole (MIC₉₀ 6.25 μ/ml), and itraconazole (MIC₉₀ 0.19 μ/ml), with the former being the most active agent tested (MFC₉₀ 3.12 μ/ml). Although amphotericin B inhibited most strains (MIC range, 0.78-3.12 μ/ml), poor fungicidal activity was observed (MFC range, 1.56 -12.5 μ/ml) showing a pattern of relative resistance In Vitro. Flucytosine showed generally poor activity against most isolates tested. These In Vitro findings confirm the resistance of T.beigelii to amphotericin B and suggest that azoles may be an alternative to the former for the treatment of disseminated trichosporonosis. However, in vivo studies would better validate these In Vitro findings.     

Evaluation of Moxifloxacin Activity In Vitro Against Mycobacterium tuberculosis,Including Resistant and Multidrug-Resistant Strains

Abstract

The new quinolone moxifloxacin was tested against 86 strains of Mycobacterium tuberculosis including 13 resistant and 4 multiresistant strains. The antimicrobial susceptibility was tested, in parallel, using two different liquid media, the radiometric Bactec 12B and the Mycobacteria Growth Indicator Tube (Becton Dickinson, USA). All strains but two were susceptible at 0.5 μg/ml of moxifloxacin; for the remaining two strains, both multidrugresistant, the minimal inhibitory concentrations (MIC) were =2 and >4 >g/ml respectively. Our data confirm the high antitubercular in vitro activity of moxifloxacin.     

Peritoneal carcinomatosis from ovarian cancer: cytoreductive surgery and intraperitoneal chemotherapy

Abstract

We tested the in vitro bactericidal activity of moxifloxacin, a new 8-methoxyquinolone, alone and in combination with vancomycin or teicoplanin at different multiples of minimum inhibitory concentration (MIC) against 8 methicillin-ciprofloxacin-resistant Staphylococcus aureus (M-C-RSA) and 1 methicillin-ciprofloxacin susceptible S. aureus (M-C-SSA) recently isolated from device-associated infections unresponsive to or relapsing after glycopeptide therapy, despite device removal. MICs of vancomycin ranged from 1 to 4 μg/ml, MICs of teicoplanin ranged from 2 to 8 μg/ml; MICs of moxifloxacin were always 2 μg/ml against M-CRSA isolates and 0.125 μg/ml against the M-C-SSA isolate. The 9 strains resulted tolerant when tested for vancomycin, teicoplanin, and moxifloxacin used alone at 2xMIC. In all cases the combination of moxifloxacin and teicoplanin or vancomycin appeared to be bactericidal already at MIC concentration for glycopeptides plus 0.5xMIC concentration for moxifloxacin. If these results are confirmed in vivo in animal experiments, the combination of moxifloxacin with glycopeptides might be useful for treating device-associated infections, and in preventing the frightening phenomenon of increasing MICs for glycopeptides.     

Susceptibility of 497 clinical isolates of gram-negative anaerobes to trovafloxacin and eight other antibiotics

Trovafloxacin is a novel investigational trifluoronaphthyridone antibiotic with broad-spectrum activity against Gram-positive and Gram-negative organisms. Its in-vitro activity and those of eight other antimicrobial agents were evaluated against 497 clinical isolates of Gram-negative anaerobic bacteria by the agar dilution method. Trovafloxacin had excellent activity, with a minimum inhibitory concentration (MIC) range of <0.03-4 microg/ml, against all species. Out of the 497 isolates tested, 496 (99.5%) were inhibited by a concentration of < or = 2.0 microg/ml of trovafloxacin; the remaining two strains were inhibited by a concentration of 4.0 microg/ml. The MIC50s and MIC90s were 0.12 microg/ml and 1.0 microg/ml, respectively. Meropenem, imipenem and piperacillin/tazobactam were also very active. Overall, at the MIC90s, trovafloxacin was as active as meropenem, slightly more active than metronidazole and imipenem, twice as active as amoxicillin-clavulanic acid, five times more active than piperacillintazobactam and 68 times more active than clindamycin. About 21% of the isolates were resistant to cefoxitin, 30% to clindamycin and 40% to piperacillin. Five species in the Bacteroides fragilis group of isolates were highly resistant to metronidazole (MIC >128 microg/ml). In general, the relatively more resistant species were the B. vulgatus, B. ovatus, B. thetaiotaomicron, and B. fragilis sensu stricto, in that order. All the isolates of the B. fragilis group and about 50% of the Prevotella spp. were beta-lactamase positive. Trovafloxacin certainly holds promise as an alternative drug for therapy of anaerobic infections.     

Oxacillin- and Mupirocin-Resistant Staphylococcus aureus: In vitro Activity of Silver Sulphadiazine and Cerium Nitrate in Hospital Strains

Abstract

Nasal carriage is an important reservoir of oxacillin-resistant Staphylococcus aureus (ORSA). Mupirocin is a topical drug used to remove S. aureus from nares. However, isolates resistant to mupirocin have been reported all over the world. Silver sulphadiazine (SSD) is a topical agent, which when associated with cerium nitrate (CN), has been shown to be useful in the treatment of burn infections and could be an alternative drug for patient decolonization. Susceptibility to oxacillin in 203 S. aureus isolates was evaluated by the agar diffusion test, while the agar diffusion and agar dilution methods were used for mupirocin. A PCR-multiplex method was performed to detect the mecA and ileS-2 genes. Minimum inhibitory concentration (MICs) to SSD and CN, used alone or in association, were determined by the agar dilution method. One hundred and sixty-three (80.3%) strains were oxacillinresistant, and 37 (18.2%) were mupirocin resistant. The MIC of SSD alone or in association with CN was 64 μg/mL, while for CN alone was 2,048 μg/mL for all isolates. SSD presented anti-staphylococcal activity at concentrations (64 μg/mL) much lower than those commonly used in commercial preparations (10 mg/g) and had good activity against mupirocin-resistant strains, showing that this drug could be used for nasal decolonization in ORSA carries.