In vitro activity of levofloxacin, ofloxacin and other quinolones against coagulase-negative staphylococci.
R. W. Johnson Pharmaceutical Research Institute, Raritan, N.J. 08869.
The in vitro activity of levofloxacin against coagulase-negative staphylococci (CNS) was investigated. In vitro, on the basis of MIC90 values, levofloxacin was as active as ciprofloxacin, inhibiting both methicillin-sensitive and -resistant staphylococci at 0.5 microgram/ml. The frequency of one-step development of levofloxacin-resistant CNS was < 1 x 10(-9). After repeated transfer of CNS in the presence of increasing concentrations of levofloxacin or other quinolones, there were 4-fold increases in MIC50 values for both levofloxacin and ofloxacin, whereas there were 64- to 128-fold increases for ciprofloxacin, norfloxacin and enoxacin. Based on MIC50 values, the concentrations of 1 or 2 micrograms/ml are clinically relevant. The mutant strains induced by levofloxacin showed less virulence based on the LD50 value in acute systemic murine infection.
Comparative in vitro activity of l-ofloxacin and FK037 to other agents against 10,040 fresh clinical isolates.
Clinical Microbiology Section, Pathology Department, Northwestern Memorial Hospital, Northwestern University Medical School, Wesley Pavilion, Room 565, 250 E. Superior Street, Chicago, IL 60611, USA.
Fresh clinical isolates collected from November 1, 1992 through November 1, 1993, were tested by agar dilution against 26 different antimicrobial agents including FK037 and l-ofloxacin. Among the 10 040 organisms tested were Staphylococcus aureus (n = 1222), methicillin-resistant Staphylococcus aureus (MRSA, n = 455), Staphylococcus epidermidis (n = 533), Staphylococcus hominis (n = 90), Staphylococcus hemolyticus (n = 89), Streptococcus pneumoniae (n = 144), Escherichia coli (n = 2326), Klebsiella pneumoniae (n = 745), Enterobacter cloacae (n = 258), Proteus mirabilis (n = 445), Pseudomonas aeruginosa (n = 998), and Stenotrophomonas (Xanthomonas) maltophilia (n = 102). Both l-ofloxacin and FK037 inhibited 98% of S. aureus strains at 4 mug/ml. FK037 was at least 4 times more effective than the third generation cephalosporins against MRSA, inhibiting 79% of the strains at 16 mug/ml. While the potency of these agents looks promising, their clinical utility will depend in part upon the maximal dosage that can be safely administered.
College of Pharmacy, Washington State University, Spokane 99201-3899, USA.
This therapeutic review discusses the pharmacology, pharmacokinetics, in vitro activity, drug interactions, and adverse effects of levofloxacin, a fluoroquinolone antibiotic. Particular emphasis is placed on the clinical efficacy of levofloxacin and its place in therapy. Compared with ciprofloxacin and the earlier quinolone agents, levofloxacin has an improved pharmacokinetic profile that allows convenient once-daily dosing in either an oral or parenteral formulation. Levofloxacin has enhanced activity against gram-positive aerobic organisms, including penicillin-resistant pneumococci. In published comparative trials involving commonly used treatment regimens, levofloxacin had equivalent if not greater activity in the treatment of community-acquired pneumonia, acute bacterial exacerbations of chronic bronchitis, acute bacterial sinusitis, acute pyelonephritis, and complicated urinary tract infection. Levofloxacin is well tolerated and induces minimal adverse drug reactions. Based on the above attributes, it may be reasonable to include levofloxacin on the hospital formulary in place of older quinolones. More recently released quinolones such as trovafloxacin exhibit similar advantages; however, until direct comparative trials between levofloxacin and these newer agents are conducted, it is difficult to advocate one agent over another. Regardless of which quinolone is the primary agent on the formulary, it is imperative that this class of antimicrobial drugs be used with discretion to minimize the development of resistance.
Multicenter, randomized study comparing levofloxacin and ciprofloxacin for uncomplicated skin and skin structure infections.
Department of Surgery, Tulane University School of Medicine, New Orleans, La 70112, USA.
BACKGROUND: The fluoroquinolone, levofloxacin, is active against most common pathogens in skin and skin structure infections. METHODS: The efficacy, tolerability, and safety of levofloxacin and ciprofloxacin were compared in a randomized, open-label, multicenter trial of patients with uncomplicated skin and skin structure infections. Of 469 patients treated, 231 received levofloxacin (500 mg qd) and 238 were given ciprofloxacin (500 mg bid). RESULTS: Overall clinical success rates (cured plus improved) for levofloxacin and ciprofloxacin were 98% and 94%, respectively (95% confidence interval [CI],-7.7, 0.7). Overall microbiologic eradication rates by patient were 98% in the levofloxacin group and 89% in the ciprofloxacin group (95% CI,-14.5,-2.7), whereas eradication rates by pathogen were 98% and 90%, respectively (95% CI,-12.6,-3.7). The eradication rate for Staphylococcus aureus was 100% in the levofloxacin group and 87% in the ciprofloxacin group (95% CI,-20.2,-5.1). Treatment-emergent adverse events were comparable, with drug-related adverse events reported in 6% of levofloxacin patients and 5% of ciprofloxacin patients. CONCLUSIONS: Levofloxacin is as effective and safe as ciprofloxacin in the treatment of uncomplicated skin and skin structure infections.
College of Pharmacy, University of Iowa (UI), Iowa City 52242-1112, USA.
The pharmacology, spectrum of activity, pharmacokinetics, clinical efficacy, and adverse effects of levofloxacin, recently approved by FDA, and trovafloxacin, currently undergoing clinical trials, are reviewed. Compared with quinolones in current use, levofloxacin is more potent against gram-negative bacteria and exhibits better antipseudomonal activity as well as greater oral bioavailability. Trovafloxacin is more potent than existing quinolones against gram-positive bacteria. Both agents exert their antibacterial effects by inhibiting bacterial DNA synthesis. Compared with other quinolones, levofloxacin and trovafloxacin both demonstrate superior activity against the Bacteroides fragilis group, Chlamydia spp., Mycoplasma pneumoniae, and Mycobacterium spp. The half-life (t1/2) of levofloxacin is nearly eight hours. Levofloxacin can therefore be administered once daily for mild to moderate infections and twice daily for more serious infections. The recommended daily dose is 500 mg. Trovafloxacin has a t1/2 of 12 hours, which allows for single daily doses, and is extensively metabolized. Levofloxacin has demonstrated clinical efficacy in the treatment of community-acquired respiratory-tract infections, genitourinary infections, skin and skin-structure infections, acute bacterial sinusitis, and infections of the head and neck. Trovafloxacin may have a role in treating skin and skin-structure or soft-tissue infections respiratory-tract infections, sexually transmitted diseases, and meningitis. Both agents are well tolerated, with central-nervous-system and gastrointestinal adverse effects reported most frequently. Concomitant administration of antacids or compounds containing meal cations decreases absorption of these quinolones. Levofloxacin and trovafloxacin have favorable antimicrobial and pharmacokinetic profiles, offering the advantages of once-daily doses as well as superior potency and spectrum of activity compared with currently available quinolones.
Institute of Medical Microbiology, Westfälische Wilhelms-Universität Münster, Germany.
The in-vitro activity of levofloxacin was compared with ofloxacin and D-ofloxacin against 130 isolates of Staphylococcus aureaus and 117 isolates of coagulase-negative staphylococci, using the agar dilution method. In general, levofloxacin was equally active or up to fourfold more active than ofloxacin against all staphylococci, including 61 methicillin-resistant S. aureus. In contrast, D-ofloxacin showed little activity against all isolates tested.
Prevalence of resistance to three fluoroquinolones: assessment of levofloxacin disk test error rates and surrogate predictors of levofloxacin susceptibility. AST Surveillance Group.
Clinical Microbiology Institute, Tualatin, Oregon 97062, USA.
More than 3,000 consecutive clinical bacterial isolates from 10 U.S. medical centers were subjected to standard broth microdilution and disk diffusion tests to determine their susceptibilities to levofloxacin, ofloxacin, D-ofloxacin, and ciprofloxacin. Levofloxacin was confirmed to be twice as active as ofloxacin and to have activity comparable to that of ciprofloxacin, with minor variations in activity against some species. The prevalence of resistant isolates was 7.1% to levofloxacin, 9.3% to ciprofloxacin, and 11.2% to ofloxacin. The susceptibilities of some species to the quinolones were less than those reported in previous studies. Pseudomonas aeruginosa isolates had the greatest variability in their susceptibilities to the three drugs between the participating centers. Two proposed zone size breakpoints for levofloxacin disk tests yielded similar low error rates. Ofloxacin and ciprofloxacin susceptibility test results correlated reasonably well with those of levofloxacin and could be used as surrogate indicators of levofloxacin susceptibility, but that resulted in some serious errors, and thus, direct testing of levofloxacin susceptibility is preferable. Replicate testing of standard quality control strains confirmed the established and proposed quality control parameters for all three quinolones tested.
Comparative prophylactic efficacies of ciprofloxacin, ofloxacin, cefazolin, and vancomycin in experimental model of staphylococcal wound infection.
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2605.
Recent shifts in the species and antibiotic resistance patterns of bacteria causing nosocomial infections present new challenges for providing effective prophylaxis in surgery. Traditional regimens lack activity against methicillin-resistant staphylococci and many gram-negative species causing nosocomial infections. The new fluoroquinolones exhibit in vitro activity against many emerging surgical wound pathogens. To determine the potential of this class of antimicrobial agents for use in surgery, we compared the prophylactic efficacies of ciprofloxacin and ofloxacin with those of cefazolin and vancomycin in a guinea pig model of abscess formation. Four Staphylococcus aureus strains, one Staphylococcus epidermidis strain, and one Staphylococcus haemolyticus strain were evaluated. Vancomycin was the most effective prophylactic agent, exhibiting in vivo activity against all strains which was superior or equivalent to those of all other agents tested. Cefazolin was the least effective agent and surpassed the two quinolones in prophylactic efficacy against only one organism, a quinolone- and methicillin-resistant strain of S. aureus. The two quinolones provided excellent protection against infection with all but the quinolone-resistant isolate. The in vivo emergence of quinolone resistance among quinolone-susceptible isolates was not detected. The methicillin-resistant, quinolone-susceptible S. epidermidis and S. haemolyticus isolates were extremely susceptible to prophylaxis, exhibiting 50% infective doses above 4 x 10(6) CFU for seven of the eight antibiotic-strain combinations. We conclude that ciprofloxacin and ofloxacin may be effective antistaphylococcal agents in surgery. The role of these agents remains to be defined, and the definition should include consideration of an adverse effect upon antibiotic resistance patterns of organisms causing nosocomial infections.
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In vitro and in vivo antibacterial activities of FK037, a novel parenteral broad-spectrum cephalosporin.
Microbiology Research, R. W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey 08869.
FK037, a new parenteral cephalosporin, is an oxime-type cephem antibiotic with a 1-hydroxyethyl-5-amino-pyrazole moiety at the 3 position. FK037 was evaluated for antimicrobial activity in vitro and in vivo. In vitro, FK037 was twofold or more active than ceftazidime, cefoperazone, cefotaxime, and ceftriaxone against Pseudomonas aeruginosa (MIC for 90% of the strains [MIC90]= 32 micrograms/ml), members of the family Enterobacteriaceae (MIC90 < or = 2 micrograms/ml), group A streptococci (MIC90 = 0.015 microgram/ml), and methicillin-sensitive or -resistant coagulase-negative staphylococci (MIC90 = 2 and 16 micrograms/ml, respectively). In addition, the activity of FK037 was equal to or greater than that of ceftazidime, cefotaxime, or ceftriaxone against Streptococcus pneumoniae (MIC90 = 0.12 microgram/ml) and methicillin-sensitive or -resistant Staphylococcus aureus (MIC90 = 2 and 16 micrograms/ml, respectively). FK037 was more active in vitro than cefepime (two- to fourfold) and cefpirome (twofold) against S. aureus. In murine systemic infection models, FK037 showed potent activity against P. aeruginosa, Escherichia coli, and methicillin-sensitive and methicillin-resistant S. aureus. FK037 was also efficacious in a mouse model of pyelonephritis caused by S. aureus or Klebsiella pneumoniae and in a mouse model of pneumococcal pneumonia caused by S. pneumoniae. Additional studies on this compound to assess its potential clinical utility are warranted.
R. W. Johnson Pharmaceutical Research Institute, Raritan, N.J. 08869.
Twelve strains of Streptococcus pneumoniae were serially exposed to increasing concentrations of levofloxacin, temafloxacin, ciprofloxacin and norfloxacin for five passages. Wild-type and passaged strains were tested for susceptibility to quinolones, macrolide and penicillin G. The MIC90 data showed a 2-fold increase for levofloxacin but a 32-fold increase for ciprofloxacin, a 16-fold increase for temafloxacin and an 8-fold increase for norfloxacin. Among 16 ciprofloxacin-induced resistant strains, 14 were susceptible to levofloxacin. No cross-resistance to other antibiotics was observed.
In vitro and in vivo antibacterial activities of levofloxacin (l-ofloxacin), an optically active ofloxacin.
Microbiology Department, R. W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey 08869-0602.
The antibacterial activity of levofloxacin was compared with those of ofloxacin, ciprofloxacin, and other antibiotics. In general, levofloxacin was equally active or up to fourfold more active than ofloxacin against all 801 organisms tested. Levofloxacin was twofold [corrected] more active than ciprofloxacin against Streptococcus pneumoniae and 2- to 4-fold more active than ciprofloxacin against Staphylococcus aureus, Xanthomonas maltophilia, and Bacteroides fragilis. Levofloxacin was two- to eightfold more active than ciprofloxacin against coagulase-negative staphylococci and Acinetobacter spp., although these improvements in potency may not be clinically relevant. Levofloxacin inhibited 90% of streptococci when it was used at concentrations of 1 to 2 micrograms/ml. Levofloxacin was two- to fourfold less active than ciprofloxacin against most members of the family Enterobacteriaceae, such as Escherichia coli; Klebsiella pneumoniae; Citrobacter, Proteus, Providencia, Salmonella, and Yersinia spp.; and Pseudomonas aeruginosa. Both compounds were equally active against Pseudomonas cepacia. The in vitro DNA gyrase inhibitory activity of levofloxacin was as potent as that of ciprofloxacin, with a 50% inhibitory concentration of 0.65 micrograms/ml against an E. coli enzyme. In vivo, oral treatment with levofloxacin was as efficacious or more efficacious than that with ciprofloxacin in systemic as well as pyelonephritis infections in mice. Levofloxacin achieved higher concentrations in the serum and tissue of mice than did ciprofloxacin. This study presents some potential advantages of the pure L isomer of ofloxacin over ciprofloxacin and other quinolones.
M Frosco, M J Pucci, L Licata, L E Lawrence, L F Discotto, B Ryan, B D Foleno, M Loeloff, J F Barrett
The RW Johnson Pharmaceutical Research Institute, Raritan, NJ 08869, USA.
The Annual Meeting of the American Society for Microbiology took place in Miami Beach, Florida, from May 4-8, 1997. Over 9000 scientists attended this meeting, which covers all major aspects of prokaryotic research (basic, applied, medical, and diagnostic). Genomics discussions were a major part of the meeting agenda, with scientists detailing both basic and applied research effort using genomics and bioinformatics. New ideas for potential novel antimicrobials have also surfaced as the tools to pursue Drug Discovery have fallen into place and pharmaceutical companies have ;rediscovered' anti-infectives.
The R. W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey 08869, USA. firstname.lastname@example.org
The bacterial enzyme MurA catalyzes the transfer of enolpyruvate from phosphoenolpyruvate (PEP) to uridine diphospho-N-acetylglucosamine (UNAG), which is the first committed step of bacterial cell wall biosynthesis. From high-throughput screening of a chemical library, three novel inhibitors of the Escherichia coli MurA enzyme were identified: the cyclic disulfide RWJ-3981, the purine analog RWJ-140998, and the pyrazolopyrimidine RWJ-110192. When MurA was preincubated with inhibitor, followed by addition of UNAG and PEP, the 50% inhibitory concentrations (IC(50)s) were 0.2 to 0.9 microM, compared to 8.8 microM for the known MurA inhibitor, fosfomycin. The three compounds exhibited MICs of 4 to 32 microg/ml against Staphylococcus aureus; however, the inhibition of DNA, RNA, and protein synthesis in addition to peptidoglycan synthesis by all three inhibitors indicated that antibacterial activity was not due specifically to MurA inhibition. The presence of UNAG during the MurA and inhibitor preincubation lowered the IC(50) at least fivefold, suggesting that, like fosfomycin, the three compounds may interact with the enzyme in a specific fashion that is enhanced by UNAG. Ultrafiltration and mass spectrometry experiments suggested that the compounds were tightly, but not covalently, associated with MurA. Molecular modeling studies demonstrated that the compounds could fit into the site occupied by fosfomycin; exposure of MurA to each compound reduced the labeling of MurA by tritiated fosfomycin. Taken together, the evidence indicates that these inhibitors may bind noncovalently to the MurA enzyme, at or near the site where fosfomycin binds.
Drug Discovery, The R. W. Johnson Pharmaceutical Research Institute, 1000 Route 202, 08869, Raritan, NJ, USA. email@example.com
Oxazolidinone antibacterial agents, where the N-substituted piperazinyl group of eperezolid was replaced with a N-substituted piperidinyloxy moiety, were synthesized and shown to be active against a variety of resistant and susceptible Gram-positive organisms. The effect of ring size, positional isomerism, and fluorine substitution on antibacterial activity was examined.
M A Weidner-Wells, K A Ohemeng, V N Nguyen, S Fraga-Spano, M J Macielag, H M Werblood, B D Foleno, G C Webb, J F Barrett, D J Hlasta
Drug Discovery, The R. W. Johnson Pharmaceutical Research Institute, 1000 Route 202, Raritan, NJ 08869, USA.
Amidino benzimidazoles have been identified as inhibitors of the bacterial KinA/Spo0F two-component system (TCS). Many of these inhibitors exhibit good in vitro antibacterial activity against a variety of susceptible and resistant Gram-positive organisms. The moiety at the 2-position of the benzimidazole was extensively modified. In addition, the regioisomeric benzoxazoles, heterocyclic replacements for the benzimidazole, have been synthesized and their activity against the TCS evaluated.
Antimicrohial Agents Research, The R. W. Johnson Pharmaceutical Research Institute, Raritan, NJ 08869, USA. firstname.lastname@example.org
Beta-lactam antibiotics such as the cephalosporins and penicillins have diminished clinical effectiveness due to the hydrolytic activity of diverse beta-lactamases, especially those in molecular classes A and C. A structure activity relationship (SAR) study of a high-throughput screening lead resulted in the discovery of a potent and selective non-beta-lactam inhibitor of class C beta-lactamases.
6-oxa isosteres of anacardic acids as potent inhibitors of bacterial histidine protein kinase (HPK)-mediated two-component regulatory systems.
R M Kanojia, W Murray, J Bernstein, J Fernandez, B D Foleno, H Krause, L Lawrence, G Webb, J F Barrett
The R. W. Johnson Pharmaceutical Research Institute, Raritan, NJ 08869-0602, USA.
A series of 6-oxa isosteres of anacardic acids (6-higher alkyl/alkenyl-2-hydroxybenzoic acids) was synthesised and several members were discovered to be among the most potent inhibitors (IC50 values < or = 5 microM) of the bacterial two-component regulatory systems, KinA/SpoOF and NRII/NRI, reported to date. The Gram-positive antibacterial activity in selected strains is also presented.
SAR studies of diaryltriazoles against bacterial two-component regulatory systems and their antibacterial activities.
Z Sui, J Guan, D J Hlasta, M J Macielag, B D Foleno, R M Goldschmidt, M J Loeloff, G C Webb, J F Barrett
R. W. Johnson Pharmaceutical Research Institute, Raritan, NJ 08869, USA.
A series of diaryltriazole analogs was discovered to inhibit bacterial two-component regulatory systems in our primary assays, KinA/Spo0F and NRII/NRI. They also showed inhibitory activity in whole cell mechanism-based assays, and they possessed potent activities against several strains of Gram-positive pathogenic bacteria in the standard MIC broth assay.
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Human recombinant lactoferrin acts synergistically with antimicrobials commonly used in neonatal practice against coagulase-negative staphylococci and Candida albicans causing neonatal sepsis.
Baylor College of Medicine & Texas Children's Hospital, 6621 Fannin, MC: WT 6-104, Houston, TX 77030, USA. email@example.com
Neonatal sepsis causes significant mortality and morbidity. Coagulase-negative staphylococci (CoNS) and Candida frequently cause neonatal sepsis at >72 h of age. Lactoferrin, which is present in human milk, is a component of innate immunity and has broad-spectrum antimicrobial activity. The synergistic effects of lactoferrin with antibiotics against neonatal isolates have not been systematically evaluated. Here, eight clinical strains (seven neonatal) of CoNS and three strains (two neonatal) of Candida albicans were studied. MIC50 and MIC90 values of human recombinant lactoferrin (talactoferrin; TLF), vancomycin (VAN) and nafcillin (NAF) against CoNS, and of TLF, amphotericin B (AMB) and fluconazole (FLC) against C. albicans, were evaluated according to established guidelines. Antimicrobial combinations of TLF with NAF or VAN against CoNS, and TLF with AMB or FLC against C. albicans, were evaluated by a checkerboard method with serial twofold dilutions. Synergy was evaluated by the median effects principle, and combination indices and dose reduction indices were reported at 50, 75 and 90% inhibitory effect at several drug-dose ratios. It was found that TLF acted synergistically with NAF and VAN against CoNS, and with AMB and FLC against C. albicans, at multiple dose effects and drug-dose ratios with few exceptions. In synergistic combinations, drug reduction indices indicated a significant reduction in doses of antibiotics, which may be clinically relevant. Thus TLF acts synergistically with anti-staphylococcal and anti-Candida agents commonly used in neonatal practice and is a promising agent that needs to be evaluated in clinical studies.
Activities of ciprofloxacin, levofloxacin, ofloxacin and sparfloxacin against speciated coagulase-negative staphylococci sensitive and resistant to fluoroquinolones.
Department of Medical Microbiology, Royal Free Hospital School of Medicine, Pond St., London NW3 2QG, UK.
A total of 119 strains of coagulase-negative staphylococci isolated from clinical specimens were speciated and tested for sensitivity to methicillin and four fluoroquinolones (ciprofloxacin, sparfloxacin, levofloxacin and ofloxacin). Resistance to fluoroquinolones was significantly more common in Staphylococcus haemolyticus (43%) than in Staphylococcus epidermidis (11%). Methicillin-resistant strains of S. haemolyticus were more often resistant to ciprofloxacin than were methicillin-resistant strains of S. epidermidis (P < 0.05). Sparfloxacin was the most active against fluoroquinolone-sensitive strains, and levofloxacin was twice as active as ofloxacin. There was cross-resistance between the four fluoroquinolones. Levofloxacin was the most active against resistant strains, but MICs obtained for all the compounds seemed to be outside the clinically useful range for the treatment of systemic infections.
School of Pharmacy, Microbiology Department,"Gr.T. Popa" University of Medicine and Pharmacy Iaşi.
UNLABELLED Gatifloxacin is in a class of drug called fluoroquinolone antibiotics. It eliminates bacteria that cause many infections, such as pneumonia and bronchitis, sinus, respiratory tract and urinary tract infections and sexually transmitted diseases. Gatifloxacin ophthalmic solution is used to treat bacterial conjunctivitis. AIM The purpose of this study was to evaluate the in vitro activity of gatifloxacin against recent 457 staphylococci, community isolates and compared it with that of pefloxacin. MATERIAL AND METHOD Powders of gatifloxacin and pefloxacin, obtained from commercial sources were tested in concentration range from 0.125 to 64 mg/l. Minimum inhibitory concentrations (MICs) were determined by the agar dilution method established by NCCLS guidelines. RESULTS The MIC 50 values for tested quinolones against coagulase-positive staphylococci are identically with MIC 90 (0.125 mg/l for gatifloxacin and 0.25 mg/l for pefloxacin respectively). Against coagulase-negative staphylococci the MICs 50 values were two-fold smaller than MICs 90 values for both gatifloxacin and pefloxacin. CONCLUSIONS Gatifloxacin was more active than pefloxacin against coagulase-positive and coagulase-negative staphylococci.
In vitro activity of daptomycin and tigecycline against coagulase-negative staphylococcus blood isolates from bone marrow transplant recipients.
Department of Medicine I, Division of Infectious Diseases and Tropical Diseases, Medical University of Vienna, Vienna, Austria.
BACKGROUND AND OBJECTIVE Multi-resistant coagulase-negative staphylococci (CNS) may cause systemic infections in patients undergoing bone marrow transplantation. Daptomycin, a new lipopeptide, and tigecycline, a new glycylcycline, have excellent activity against Gram-positive bacteria including methicillin-resistant staphylococci. This study presents the in vitro activity of daptomycin and tigecycline compared to vancomycin and fosfomycin against 105 CNS isolated from 76 bone marrow transplant patients with symptomatic bacteremia. MATERIAL AND METHODS Blood stream isolates of Staphylococcus epidermidis (n = 102) and Staphylococcus haemolyticus (n = 3) from bone marrow transplant patients were collected from 2000 to 2006. The susceptibility of all isolates was tested using methods of the Clinical Laboratory Standards Institute. RESULTS The minimal inhibitory concentrations MIC(50) and MIC(90) were 0.125 microg/mL and 0.25 microg/mL for daptomycin, 0.25 and 0.5 microg/mL for tigecycline, 1 microg/mL and 2 microg/mL for vancomycin, and 8 microg/mL and >256 microg/mL for fosfomycin, respectively. MIC values of tested agents were similar for both methicillin-sensitive and methicillin-resistant S. epidermidis strains. CONCLUSIONS All CNS isolates were susceptible to the new antistaphylococcal agents daptomycin and tigecycline. Although vancomycin had been used over the past 30 yr at our bone marrow transplant unit all CNS were still susceptible to vancomycin.
Activities of clindamycin, synercid, telithromycin, linezolid, and mupirocin against Gram-positive coccal strains resistant to erythromycin in Korea.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151742, Korea.
The antibacterial activities of clindamycin, synercid, telithromycin, linezolid and mupirocin were evaluated against erythromycin-resistant Gram-positive coccal clinical isolates collected in Korean hospitals. In Staphylococcus aureus, synercid, linezolid and mupirocin were the most active agents. Against coagulase-negative staphylococci (CNS), synercid, linezolid and mupirocin were also active. Telithromycin and synercid resistance was common against enterococci, only linezolid and mupirocin were active. The reason of low activity of telithromycin against staphylococci and enterococci is because most of the isolates were constitutively resistant to erythromycin. Synercid, telithromycin, linezolid and mupirocin were active against streptococci.
Disciplina de Microbiologie, Facultatea de Farmacie, Universitatea de Medicină Si Farmacie "Gr. T. Popa", Iaşi.
UNLABELLED Cefpirome is a fourth-generation cephalosporin with an expanded spectrum against both Gram-negative and Gram-positive bacteria. The objective of this study was to evaluate the in vitro activity of cefpirome against staphylococci, clinical isolates. For comparison oxacillin was also tested. MATERIAL AND METHODS A total 434 isolates (coagulase-positive staphylococci, n = 268 and coagulase-negative staphylococci, n = 166) were tested. Susceptibility testing was performed using the Mueller-Hinton agar dilution method. RESULTS Cefpirome inhibited the majority of strains at 0.5-8 mg/l. Cefpirome had excellent activity against coagulase-negative staphylococci with 91.6% susceptibility. Except the coagulase-positive staphylococci, of the 268 isolates, 81.3% were cefpirome sensitive. Concerning oxacillin, 35.1% of coagulase-positive staphylococci isolates were resistant, comparative with 26.5% of the coagulase-negative staphylococci. A cross-resistance analysis showed the association of resistance between cefpirome and oxacillin. CONCLUSION Against staphylococci, cefpirome had the best activity when compared with the oxacillin.
Shanghai Institute of Materia Medica, Shanghai Institute for Biological Science, Chinese Academy of Sciences Shanghai 201203, China. firstname.lastname@example.org
OBJECTIVES AND METHODS YC-20 is a novel oxazolidinone that has targeted activity against Gram-positive bacteria. The in vitro activity of YC-20 and 6 comparators against 522 clinical isolates of Gram-positive species was determined. RESULTS YC-20 is a potent oxazolidinone with all isolates tested displaying MIC50 and MIC90 values of <0.5 and 2 mg/L, respectively. MICs of YC-20 for all isolates tested, with the exception of methicillin-susceptible Staphylococcus epidermidis, were similar or lower than those of linezolid. CONCLUSIONS This study suggests a potential new antibiotic for the treatment of infections with Gram-positive bacteria.
In vitro activities of 11 fluoroquinolones against 816 non-typhoidal strains of Salmonella enterica isolated from Finnish patients with special reference to reduced ciprofloxacin susceptibility.
Department of Bacterial and Inflammatory Diseases, National Public Health Institute, Turku, Finland. email@example.com
BACKGROUND: The number of Salmonella strains with reduced susceptibility to fluoroquinolones has increased during recent years in many countries, threatening the value of this antimicrobial group in the treatment of severe salmonella infections. METHODS: We analyzed the in vitro activities of ciprofloxacin and 10 additional fluoroquinolones against 816 Salmonella strains collected from Finnish patients between 1995 and 2003. Special attention was focused on the efficacy of newer fluoroquinolones against the Salmonella strains with reduced ciprofloxacin susceptibility. RESULTS: The isolates represented 119 different serotypes. Of all 816 Salmonella strains, 3 (0.4%) were resistant to ciprofloxacin (MIC > or = 4 microg/ml), 232 (28.4%) showed reduced susceptibility to ciprofloxacin (MIC > or = 0.125-2 microg/ml), and 581 (71.2%) were ciprofloxacin-susceptible. The MIC50 and MIC90 values of ciprofloxacin for these strains were 0.032 and 0.25 microg/ml, respectively, being lower than those of the other fluoroquinolone compounds presently on market in Finland (ofloxacin, norfloxacin, levofloxacin, and moxifloxacin). For two newer quinolones, clinafloxacin and sitafloxacin, the MIC50 and MIC90 values were lowest, both 0.016 and 0.064 microg/ml, respectively. Moreover, clinafloxacin and sitafloxacin exhibited the lowest MIC50 and MIC90 values, 0.064 and 0.125 microg/ml, against the 235 Salmonella strains with reduced susceptibility and strains fully resistant to ciprofloxacin. CONCLUSION: Among the registered fluoroquinolones in Finland, ciprofloxacin still appears to be the most effective drug for the treatment salmonella infections. Among the newer preparations, both clinafloxacin and sitafloxacin are promising based on in vitro studies, especially for strains showing reduced ciprofloxacin susceptibility. Their efficacy, however, has not been demonstrated in clinical investigations.
Tatiana Bogdanovich, Duygu Esel, Linda M Kelly, Bülent Bozdogan, Kim Credito, Gengrong Lin, Kathy Smith, Lois M Ednie, Dianne B Hoellman, Peter C Appelbaum
Department of Pathology, Hershey Medical Center, P.O. Box 850, Hershey, PA 17033, USA. firstname.lastname@example.org
The in vitro activity of DX-619, a new des-F(6)-quinolone, was tested against staphylococci and compared to those of other antimicrobials. DX-619 had the lowest MIC ranges/MIC(50)s/MIC(90)s (microg/ml) against 131 Staphylococcus aureus strains (</=0.002 to 2.0/0.06/0.5) and 128 coagulase-negative staphylococci (0.004 to 0.25/0.016/0.125). Among strains tested, 76 S. aureus strains and 51 coagulase-negative staphylococci were resistant to ciprofloxacin. DX-619 had the lowest MIC(50)/MIC(90) values against 127 quinolone-resistant staphylococci (0.125/0.5), followed by sitafloxacin (0.5/4), moxifloxacin (2/8), gatifloxacin (4/16), levofloxacin (16/>32), and ciprofloxacin (>32/>32). Raised quinolone MICs were associated with mutations in GyrA (S84L) and single or double mutations in GrlA (S80F or Y; E84K, G, or V) in all S. aureus strains tested. A recent vancomycin-resistant S. aureus (VRSA) strain (Hershey) was resistant to available quinolones and was inhibited by DX-619 at 0.25 microg/ml and sitafloxacin at 1.0 microg/ml. Vancomycin (except VRSA), linezolid, ranbezolid, tigecycline, and quinupristin-dalfopristin were active against all strains, and teicoplanin was active against S. aureus but less active against coagulase-negative staphylococci. DX-619 produced resistant mutants with MICs of 1 to >32 microg/ml after <50 days of selection compared to 16 to >32 microg/ml for ciprofloxacin, sitafloxacin, moxifloxacin, and gatifloxacin. DX-619 and sitafloxacin were also more active than other tested drugs against selected mutants and had the lowest mutation frequencies in single-step resistance selection. DX-619 and sitafloxacin were bactericidal against six quinolone-resistant (including the VRSA) and seven quinolone-susceptible strains tested, whereas gatifloxacin, moxifloxacin, levofloxacin, and ciprofloxacin were bactericidal against 11, 10, 7, and 5 strains at 4x MIC after 24 h, respectively. DX-619 was also bactericidal against one other VRSA strain, five vancomycin-intermediate S. aureus strains, and four vancomycin-intermediate coagulase-negative staphylococci. Linezolid, ranbezolid, and tigecycline were bacteriostatic and quinupristin-dalfopristin, teicoplanin, and vancomycin were bactericidal against two, eight, and nine strains, and daptomycin and oritavancin were rapidly bactericidal against all strains, including the VRSA. DX-619 has potent in vitro activity against staphylococci, including methicillin-, ciprofloxacin-, and vancomycin-resistant strains.
National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa.
OBJECTIVES To determine the susceptibility of southern African strains of Yersinia pestis to novel as well as conventional antimicrobial agents. MATERIALS AND METHODS The MICs of 28 strains of Yersinia pestis from a southern African plague focus were determined by agar dilution. RESULTS The most active agents were cefditoren and the fluoroquinolones, both conventional and novel. The in vitro activity of macrolides was poor against this member of the Enterobacteriaceae. CONCLUSION Further investigation of the novel quinolones olamufloxacin (HSR 903) and ABT 492 in animal models of plague would seem to be justified.