Susceptibility of Ureaplasma urealyticum to tetracycline, doxycycline, erythromycin, roxithromycin, clarithromycin, azithromycin, levofloxacin and moxifloxacin

The in vitro activity of tetracycline, doxycycline, erythromycin, roxithromycin, clarithromycin, azithromycin, levofloxacin and moxifloxacin was tested against 63 clinical isolates of Ureaplasma urealyticum. The minimal inhibitory concentrations (MICs) and the minimal bactericidal concentrations (MBCs) were determined by the broth microdilution method in A7 medium. The MIC(50) and MIC(90) of the tested agents after 24 h of incubation were as follows: tetracycline, 0.5 and 2.0 μg/ml; doxycycline, 0.125 and 0.25 μg/ml; erythromycin, 2.0 and 8.0 μg/ml; roxithromycin, 2.0 and 4.0 μg/ml; clarithromycin, 0.25 and 1.0 μg/ml; azithromycin, 2.0 and 4.0 μg/ml; levofloxacin, 1.0 and 2.0 μg/ml; and moxifloxacin, 0.5 and 0.5 μg/ml, respectively. The MIC values after 24 h and 48 h incubation differed by no more than one dilution for all the agents with the exception of doxycycline (two dilution difference for MIC(90)). Overall, moxifloxacin was the most active agent in vitro against U. urealyticum, with the narrowest difference between MIC and MBC values, followed closely by levofloxacin. Clarithromycin was the most active macrolide.     

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.     

In Vitro Activity of HMR 3647 Against Anaerobic Bacteria

Abstract

The aim of the present investigation was to determine the In Vitro activity of HMR 3647 compared with other antimicrobial agents against anaerobic bacteria. The activity of HMR 3647 was determined against 342 clinical isolates of anaerobic bacteria by the agar dilution method and was compared with azithromycin, clarithromycin, roxithromycin, erythromycin, cefoxitin, imipenem, clindamycin and metronidazole.

Among the macrolides HMR 3647 and among the beta-lactams imipenem were the most active agents tested. Anaerobic cocci (50 strains) had the following minimum inhibitory concentrations (MICs): HMR 3647, range 0.016-0.125 mg/l; imipenem, range 0.016-0.064 mg/l. Propionibacterium acnes (30 strains): HMR 3647, 0.016-1.0 mg/l; imipenem, 0.032-0.064 mg/l. Clostridium perfringens (30 strains): HMR 3647, 0.125 mg/l; imipenem, 0.016-0.5 mg/l. Clostridium difficile (50 strains): HMR 3647, 0.125-256 mg/l; imipenem, 4.0-8.0 mg/l. Bacteroides fragilis (102 strains): HMR 3647, 0.032-16 mg/l; imipenem, 0.064-0.25 mg/l. Bacteroides and Prevotella species (50 strains): HMR 3647, 0.016-4.0 mg/l; imipenem, 0.016-0.25 mg/l. Fusobacterium nucleatum (30 strains): HMR 3647, 0.016-8.0 mg/l; imipenem, 0.008-0.064 mg/l.

HMR 3647 may be useful as treatment and prophylaxis for infections due to anaerobic bacteria.     

In vitro selection of resistance to clarithromycin in Streptococcus pneumoniae clinical isolates

In this study the effects of exposure to serum, lung and breakpoint concentrations on Streptococcus pneumoniae susceptibility to clarithromycin, azithromycin, amoxicillin/clavulanate, levofloxacin and moxifloxacin were evaluated. Development of resistance was determined by multi-step and single-step methodologies. In the first experimental set, minimum inhibitory concentrations (MICs) were determined after 10 passages on antibiotic-gradient plates and 10 passages on antibiotic-free plates. Acquisition of resistance was defined as an increase of > or = 4-fold from the starting MIC. In single-step studies, the rate of spontaneous mutations was calculated after a passage on antibiotic-containing agar plates. Azithromycin and levofloxacin gave the highest number of strains with MIC increased of at least 4 times the starting value, followed by moxifloxacin and by clarithromycin which only at the lowest concentration tested selected for resistance in 5 strains. Amoxicillin/clavulanate never displayed > or = 4-fold MIC increase. Frequencies of mutation were lower for clarithromycin and moxifloxacin than for the comparators. At lung concentrations clarithromycin had limited potential to select for resistance.     

An Update on Invasive Pneumococcal Antibiotic Resistance in Turkey, 2008

Abstract

Cumulative pneumococcal antibiotic resistance profiles in Turkey in 2008, verified from local studies are as follows: penicillin 35%, cefotaxime 2%, ceftriaxone 1%, trimethoprim-sulfamethoxazole 39%, tetracycline 19%, erythromycin 18%, azithromycin 18%, clarithromycin 10%, ofloxacin 13%, clindamycin 9%, chloramphenicol 5%, rifampicin 2%, levofloxacin 2%, moxifloxacin 0%, gemiloxacin 0%, telithromycin 0%, vancomycin 0%.     

Moxifloxacin sensitivity of respiratory pathogens in the United Kingdom

The in vitro activity of moxifloxacin and comparator agents against respiratory isolates from a range of geographically distinct centres around the United Kingdom was investigated in the following study. Clinical isolates of Streptococcus pneumoniae (n = 257), Haemophilus influenzae (n = 399) and Moraxella catarrhalis (n = 253) were obtained between March 1998 and April 1999 from nine centres in the United Kingdom. Sensitivity was determined by testing each isolate for its minimum inhibitory concentration (MIC) by agar dilution. Against Streptococcus pneumoniae moxifloxacin and grepafloxacin were the most active (MIC90 = 0.25 mg/l). Trovafloxacin and sparfloxacin were the next most active (MIC90 = 0.5 mg/l) followed by levofloxacin and ciprofloxacin. MIC90 values of the six fluoroquinolones versus H. influenzae ranged from <0.0039 mg/l to 0.0625 mg/l and from <0.0039 mg/l to 0.5 mg/l for M. catarrhalis. The rank order of activity of the fluoroquinolones versus H. influenzae was moxifloxacin = trovafloxacin = grepafloxacin = sparfloxacin > ciprofloxacin > levofloxacin. Against M. catarrhalis the lowest MIC90 was that of grepafloxacin at 0.0625 mg/l followed by moxifloxacin, sparfloxacin, levofloxacin and ciprofloxacin. Trovafloxacin demonstrated the highest MIC90 at 0.5 mg/l. These results demonstrate that moxifloxacin has superior in vitro activity against respiratory tract pathogens than any other comparator quinolones available for clinical use.     

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.     

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.     

Antimicrobial susceptibility profile of contemporary clinical strains of Stenotrophomonas maltophilia isolates: can moxifloxacin activity be predicted by levofloxacin MIC results?

The susceptibility profile of 763 Stenotrophomonas maltophilia isolates was evaluated against 16 antimicrobials by the CLSI reference broth microdilution method. Minocycline (MIC(90), 1 microg/ml; 100.0% susceptible) was the most active compound, followed by doxycycline (MIC(90), 4 microg/ml; 99.6% susceptible), trimethoprim/sulfamethoxazole (MIC(90), 1 microg/ml; 97.8% susceptible), and tigecycline (MIC(90), 2 microg/ml). An excellent correlation between levofloxacin (MIC(90), 4 microg/ml; 86.5% susceptible by published breakpoint criteria) and moxifloxacin (MIC(90), 2 micro g/ml) MIC results was observed indicating that moxifloxacin could be further evaluated as a therapeutic option for S. maltophilia infections.     

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.     

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.     

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).     

In- Vitro Susceptibility of Borrelia burgdorferi and Borrelia hermsii to Ten Antimicrobial Agents

Summary

The in-vitro activity of ten antimicrobial agents against four strains of Borrelia burgdorferi originating both in the United States and Europe and against one isolate of B. hermsii was investigated. Ceftriaxone, erythromycin and roxithromycin were the most active drugs against both Borrelia species studied, with minimum bactericidal concentrations ranging from 0.015 μg/ml to 0.125 μ/ml.     

Prosthetic Biologic Valve Endocarditis Caused by a Vancomycin-Resistant (vanA) Enterococcus faecalis: Case Report

Abstract

We recently observed (February 1999) a 68-year old patient with endocarditis on a prosthetic biologic valve caused by a vancomycin-resistant Enterococcus faecalis. Broth dilution tests showed susceptibility to ampicillin (MIC=0.5 μg/ml), no high resistance to aminoglycosides (MIC for gentamicin <500 μg/ml) and resistance to vancomycin (MIC >256 μg/ml) and teicoplanin (MIC>16 μg/ml). A PCR assay detected vanA gene in this strain. A trans-thoracic echocardiogram did not show valvular vegetations. A possible endocarditis was diagnosed and the patient received ampicillin for 8 weeks and gentamicin for 6 weeks. The patient remained afebrile after a 4-month follow-up when he underwent surgical replacement of the dysfunctional bioprosthetic valve. Mitral valve was sterile on culture, but histology confirmed the diagnosis of previous endocarditis. This is the third case of endocarditis caused by vancomycin-resistant E. faecalis reported to date.     

Annual Author and Subject Indexes Volume 18-2006

Abstract

Resistant clones/phenotypes are putting into question the activity of commonly used β-lactams, thus prompting the need for alternative options. A 500 mg levofloxacin vs. azithromycin once daily pharmacodynamic simulation was performed against 10⁸ cfu/ml of four Streptococcus pneumoniae strains (exhibiting higher amoxicillin than penicillin MIC) and four Haemophilus influenzae strains: β-lactamase producing, BLNAR (β-lactamase-negative ampicillin-resistant) and BLPACR (β- lactamase-positive amoxicillin/clavulanate-resistant). High levofloxacin AUC/MIC values for H. influenzae, and values of 50-100 for S. pneumoniae produced a >5 log₁₀ reduction at 24h for all strains. Azithromycin AUC/MIC values of ?10 were needed to obtain a 2-3 log₁₀ reduction of S. pneumoniae initial inocula, but lower AUC/MIC values (of ?6) obtained ≥3 log₁₀ reduction against all strains of H. influenzae. While in vitro simulated serum concentrations of levofloxacin were bactericidal at the end of the dosing interval against all S. pneumoniae strains and azithromycin against the susceptible ones, both antimicrobials achieved this endpoint against the BLNAR and BLPACR strains.     

The role of newer macrolides in the treatment of community-acquired respiratory tract infection. A review of experimental and clinical data.

The macrolide class of antibiotics is well established and often recommended for use in the treatment of community-acquired respiratory tract infection (RTI). The newer agents clarithromycin and azithromycin are frequently prescribed as first- or second-line therapy, and have been considered as superior to erythromycin in microbiological activity and clinical efficacy. In-vitro data show that clarithromycin and azithromycin have good activity (MIC < or = 0.5 microg/ml) against certain RTI pathogens. However the activity of both compounds is intrinsically low against Haemophilus influenzae whilst several other important RTI pathogens - notably Streptococcus pneumoniae and Streptococcus pyogenes - exhibit a high prevalence of resistance to them. In many countries, the prevalence of resistance to clarithromycin and azithromycin is still rising with cross resistance with erythromycin. Maximum serum concentrations of clarithromycin and azithromycin are lower than the MIC90s for these agents against H. influenzae and S. pneumoniae. Concentrations in tissues have been reported to be much higher than those in serum. However, the high concentrations observed in tissues are largely a reflection of high concentrations inside cells. Concentrations of clarithromycin and azithromycin in extracellular tissue fluids, where Haemophilus and streptococci are located, are in equilibrium with concentrations in the serum, and remain low. It has been suggested that phagocytes deliver azithromycin to infection sites in a targeted fashion, but the evidence in support of this hypothesis is weak. Recent clinical experience with clarithromycin and azithromycin is consistent with preclinical results, and suggests that these agents have limited efficacy against certain respiratory infections. Clarithromycin and azithromycin are the first choice treatment of atypical infections caused by intracellular pathogens. For community-acquired RTIs, where H. influenzae and S. pneumoniae are present, they may no longer be an appropriate choice for first-line therapy. Indeed, in areas where levels of drug resistant S. pneumoniae are high, their use may be questionable as second-line therapy.     

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.     

In Vivo Pharmacodynamic Evaluation of Clarithromycin in Comparison to Erythromycin

Abstract

The efficacy of various dosing regimens of clarithromycin and erythromycin against recently isolated Streptococcus pneumoniae strains was determined In Vivo using two animal infection models (mouse peritonitis and thigh infection). For the thigh infection model, mice received a total dose of 4 mg/Kg of either clarithromycin or erythromycin, as a single total dose or divided into 2, 4 or 8 doses/24h. After 24h of therapy S. pneumoniae organisms were killed at 2.06 to 4.03 log₁₀ CFU/thigh by clarithromycin and the one- or two-dose regimens were significantly more effective than the four- or eight-dose regimens. Organism killing following 24h of therapy with erythromycin ranged from 1.13 to 2.31 log₁₀ CFU/thigh, with the one- or two-dose regimens significantly less effective than the four- or eight-dose regimens. In the mouse survival study, the same dose of either clarithromycin or erythromycin was given as a single total dose or divided into two or four doses with dosing intervals of 4 and 2-times the t_1/2 respectively. The results obtained in this model show that there is a significant difference in survival when clarithromycin is administered less frequently (4% deaths for the one-dose regimen in comparison to 40% deaths with the four-dose regimen, P<0.01, Chisquare test). With erythromycin there was a trend for increased survival with the multiple-dose regimen, with significantly higher survival when concentrations exceeding the MIC were maintained for a longer time period. These results indicate that the time during which serum concentrations exceeding the MIC value of the pathogen is an important parameter for efficacy for erythromycin. On the contrary, results with both animal models demonstrate that bacterial killing and survival are significantly higher among clarithromycin-treated mice when the antibiotic is administered less frequently and the highest Cmax/MIC ratio is achieved.     

Inhibitory and Bactericidal Activity of Rokitamycin against Helicobacter pylori and Morphological Alterations

Abstract

Rokitamycin is a macrolide antibiotic, recently entered into clinical use. Its in vitro activity and kill kinetics against Helicobater pylori have been evaluated at 1 x the minimum inhibitory concentration (MIC), 2×MIC and 4×MIC at 2, 4, 8, 24 hours and compared with those of clarithromycin, erythromycin and amoxicillin. Morphological changes in H. pylori induced by rokitamycin incubation at these MICs and times were also investigated by scanning electron microscopy. All the antibiotics tested had good inhibitory activity against H. pylori, a slow growing microorganism. The order of MIC activity was clarithromycin > amoxicillin > rokitamycin > erythromycin. Rokitamycin killed more rapidly than the other antibiotics, in fact H. pylori strains were totally killed at 8 h (2×MIC) and 4 h ( 4×MIC) and after only 2h incubation all concentrations greatly decreased the CFU/ml. These effects were also confirmed by the rapid appearance of surface and morphological alterations (focal blebs, constrictions, rounded forms) in the normal structure of H. pylori observed by scanning electron microscopy. Clinical studies should be conducted to investigate the in vivo activity of rokitamycin, as an agent to be used in the combination therapies against H. pylori.     

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).