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In vitro activity of levofloxacin against recent Gram-negative nosocomial pathogens.

The objective of our study was to evaluate the in vitro activity of levofloxacin in comparison with other antibiotics (coamoxiclav, ceftriaxone, ceftazidime, meropenem, aztreonam, ciprofloxacin and netilmicin) against about 500 Gram-negative nosocomial microorganisms, isolated during 2003. The bactericidal activities (minimal bactericidal activity and killing curve) of levofloxacin and the other antibiotics were also evaluated. The results confirm the excellent in vitro activity of levofloxacin against multiresistant nosocomial Gram-negative pathogens, including the 73 extended spectrum beta-lactamase producer strains (90% of Escherichia coli, Enterobacter cloacae and Klebsiella pneumoniae were inhibited at 0.5 mg/l). Of particular interest is its susceptibility and bactericidal activity against Stenotrophomonas maltophilia strains. In conclusion, due to the favorable pharmacokinetics and pharmacodynamics of the molecule, associated with its safety, levofloxacin may represent a valid therapeutic option in the treatment of severe Gram-negative nosocomial infections.

Anti-Bacterial Agents↗

Combined effects of panipenem and aminoglycosides on methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa in vitro.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are the main causes of refractory infections that are often resistant to antimicrobial agents. In these cases, combination of agents with antimicrobial activity is being examined. However, few studies have investigated combined effects with antimicrobial agents including carbapenem and aminoglycosides. METHODS: We evaluated the effects of panipenem (PAPM) combined with 3 aminoglycosides, arbekacin, amikacin, and netilmicin, and vancomicin (VCM) with an agar dilution checkerboard technique and the fractional inhibitory concentration index against 47 strains of MRSA and 56 strains of P. aeruginosa. RESULTS: PAPM combined with VCM achieved a synergic effect against MRSA in 80.9%. PAPM combined with aminoglycosides showed only additive effects against MRSA and P. aeruginosa. When comparing the activity of Mueller-Hinton agar (MHA) medium with MHA medium diluted 40-fold (1/40 MHA) against P. aeruginosa, the mean minimum inhibitory concentration of PAPM was decreased to 1/16. CONCLUSIONS: Combination of PAPM and VCM is effective against MRSA. Combinations of PAPM and aminoglycosides showed additive effects against MRSA and P. aeruginosa.

Aminoglycosides↗

Prevalence and antimicrobial resistance patterns of Aeromonas strains isolated from drinking water samples in istanbul, Turkey.

The aim of this study was to determine the prevalence and the resistance patterns of Aeromonas spp. in drinking water in Istanbul, Turkey. We investigated a total of 1,680 drinking water samples (840 tap water and 840 domestic water tank samples) for Aeromonas strains between June 2002 and October 2005. A total of 147 Aeromonas strains were isolated from 49 (6%) of 840 tap water samples and from 98 (12%) of 840 domestic water tank samples. Antibiotic susceptibility of Aeromonas strains was determined by the disc diffusion method, according to the CLSI (Clinical Laboratory Standards Institute) recommendation. Among the 147 Aeromonas strains, the prevalence was: A. hydrophila 68 (46%), A. sobria 50 (34%), A. caviae 11 (8%), A. salmonicida 9 (6%), A. veronii 5 (3%) and A. jandaei 4 (3%). Approximately 55% of the strains were resistant to ampicillin, 48% to erythromycin, 41% to amoxicillin-clavulanic acid, 28% to ceftazidime, 27% to cefoxitin, 26% to ceftriaxone and cefotaxime, 22% to piperacillin, 14% to trimethoprim-sulfamethoxazole, 12% to tetracycline, 11% to aztreonam, 8% to meropenem, 6% to imipenem, 2% to nalidixic acid, 1% to ciprofloxacin, tobramycin and gentamicin. None of the strains were resistant to amikacin and netilmicin. In conclusion, Aeromonas spp. isolated from drinking water in Istanbul have a resistance potential and the antibiotic resistance rates of A. hydrophila, A. sobria and A. caviae were usually higher than those of other Aeromonas strains. It should be kept in mind that these microorganisms in drinking water might be a potential risk for public health.

Aeromonas↗

Combination effect of piperacillin with four aminoglycosides on nonfermenting gram-negative bacteria.

The in vitro efficacy of piperacillin in combination with gentamicin, tobramycin, amikacin and netilmicin against 57 nonfermenting gram-negative bacterial strains was compared by use of the checkerboard agar dilution technique. On average 34% of all nonfermenting strains were inhibited by additive, 13% by synergistic piperacillin-amino-glycoside combinations. Great variation occurred between the different bacterial species. Piperacillin-aminoglycoside combinations were most active on Pseudomonas aeruginosa and least potent on Pseudomonas cepacia. Piperacillin was highly active against P. aeruginosa, P. cepacia, Pseudomonas fluorescens-putida and Acinetobacter species.

Aminoglycosides↗

Combination effect of ceftriaxone with four aminoglycosides on nonfermenting gram-negative bacteria.

The in vitro efficacy of ceftriaxone in combination with gentamicin, tobramycin, amikacin and netilmicin against 50 nonfermenting gram-negative bacterial strains was compared by use of the checkerboard agar dilution technique. On average 42.5% of all nonfermenting strains were inhibited by additive, 22.5% by synergistic ceftriaxone-aminoglycoside combinations. Great variations occurred between the different bacterial species. Ceftriaxone-tobramycin interactions were superior to combinations with other aminoglycosides. Ceftriaxone-aminoglycoside combinations were most active on Pseudomonas aeruginosa and least potent on Pseudomonas cepacia.

Aminoglycosides↗

Plasmid-independent resistance of 'gray' colony variants of a strain of Serratia marcescens resistant to amikacin, cefotaxime and lamoxactam.

A multiple-drug-resistant strain of Serratia marcescens (serotype O14:H12; bacteriocin type 18), which was recovered repeatedly from the respiratory tract of an intensive care unit patient, yielded 'gray' colony phenotypic variants which were greater than or equal to four-fold less susceptible to amikacin, cefotaxime, and lamoxactam, but not to netilmicin and N-formimidoyl thienamycin, as compared with 'opaque' (wild-type) colony variants. The 'gray' variants proved phenotypically highly unstable and displayed comparable low virulence for NMRI mice (intraperitoneal route). The 'opaque' and 'gray' variants of this strain carried a nonconjugative, 46-megadalton resistance (R) plasmid, as determined by DNA agarose gel electrophoresis. The R-plasmid-mediated resistance against chloramphenicol, gentamicin, kanamycin, mezlocillin, piperacillin, triple sulfonamides, and cotrimoxazole, as demonstrated with 'curing' experiments. The mechanism of the novel amikacin-beta-lactam antibiotic resistance phenomenon remained undetermined.

Amikacin↗

Combined defibrinated human blood and antimicrobial drug activities against Enterobacter cloacae.

The combinations of 11 antimicrobial drugs and fresh human defibrinated blood were examined for potential additive effects against several isolates of Enterobacter cloacae recovered from patients with bacteremia or meningitis. Aminoglycosides (amikacin, gentamicin, netilmicin) proved most efficacious, followed by cephalosporins (lamoxactam, cefotaxime, ceftizoxime) and ureidopenicillins (mezlocillin, piperacillin). Nalidixic acid, nitrofurantoin, and cotrimoxazole yielded indifferent effects. The E. cloacae isolates displayed low virulence for outbred NMRI mice.

Animals↗

Efficacy of apalcillin alone and in combination with four aminoglycoside antibiotics against Pseudomonas aeruginosa.

The in vitro activity of apalcillin against 258 Pseudomonas aeruginosa strains was compared with that of 3 penicillins and 5 aminoglycosides using agar dilution tests. Apalcillin showed the highest activity of all the penicillins investigated, and of the aminoglycosides tested tobramycin and amikacin were most active. On testing the combined efficacy of apalcillin with aminoglycosides by the checkerboard technique, combinations with tobramycin or amikacin were less synergistic than combinations with gentamicin or netilmicin. Antagonistic or even only additive effects were found with none of the P. aeruginosa strains.

Aminoglycosides↗

Pseudomonas aeruginosa: in vitro susceptibility to antimicrobial drugs, single and combined, with and without defibrinated human blood.

Twelve clinical isolates of Pseudomonas aeruginosa of distinct pyocin type varied in susceptibility to 14 of 17 antimicrobial drugs. The 2 x MIC concentrations of 16 antimicrobial drugs combined with 55% (v/v) of fresh, defibrinated human blood yielded additive effects. Additive effects were noted with blood plus the MIC concentrations of all drugs tested except cefoperazone, gentamicin, and netilmicin. Blood combined with subinhibitory (1/2 MIC) concentrations of aztreonam, ceftazidime, ciprofloxacin, fleroxacin, imipenem, and tobramycin, respectively, yielded additive effects; indifferent effects were observed with the remaining 10 blood plus 1/2 MIC drug combinations. The following drug combinations additively augmented the antibacterial activity of 65% (v/v) of human blood against two selected isolates of P. aeruginosa: tobramycin (1 microgram/ml) plus the MIC or 2 x MIC concentrations of azlocillin, aztreonam, ceftazidime, ciprofloxacin, imipenem, norfloxacin, ofloxacin, piperacillin, and ticarcillin, respectively. Imipenem (8 micrograms/ml) combined with ceftazidime, cefoperazone, and piperacillin, but not aztreonam, enhanced the bactericidal activity of human blood. Rifampin (2 micrograms/ml) plus tobramycin (0.5-1 microgram/ml) combined with 8 or 16 micrograms/ml of azlocillin, aztreonam, cefoperazone, ceftazidime, imipenem, and piperacillin, respectively, enhanced blood-mediated killing of three representative multiple-drug-resistant P. aeruginosa isolates. Additional effective triple-drug combinations with human blood were rifampin + tobramycin + polymyxin B, rifampin + ciprofloxacin + imipenem, and rifampin + amikacin + imipenem. Ciprofloxacin (2 micrograms/ml) was the most potent intraphagocytic bactericidal drug of 16 tested agents (greater than or equal to 2 x MBC concentrations) against P. aeruginosa control strain ATCC 27853.

Anti-Bacterial Agents↗

In vitro activities of A-56619 (difloxacin) and A-56620, two aryl fluoroquinolones.

The in vitro activities of A56619 (difloxacin) and A-56620, two newer quinolones, have been compared with the activities of ciprofloxacin, ofloxacin, ceftazidime and netilmicin. A total of 782 clinical, bacterial isolates were employed. Minimal inhibitory concentrations (MICs) were determined under standard conditions with all isolates and, for 100 isolates against difloxacin and A-56620, with variation of agar pH and bacterial inoculum size. On a weight-for-weight basis, ciprofloxacin and A-56620 were the most active agents against Enterobacteriaceae (MIC90 = 0.03 and 0.12 mg/l, respectively). Difloxacin was the least active quinolone, particularly against Proteus, Morganella and Providencia spp. Except for ceftazidime, all agents were highly active against staphylococci, but difloxacin and ofloxacin were somewhat less active against Staphylococcus saprophyticus. The streptococcal isolates were moderately sensitive to the quinolones, difloxacin being least active. Haemophilus influenzae and Neisseria gonorrhoeae were extremely susceptible to all the quinolones; nearly all isolates were inhibited by the lowest concentrations of the agents that were employed in the study (0.03 mg/l). The quinolones all showed moderate activity against Bacteroides fragilis. The activities of difloxacin and A-56620 were affected little by inoculum size. Difloxacin showed lower activity against most isolates at pH 8.0 as compared to the activity at pH 7.4 and 6.8. A-56620 was minimally influenced by pH variation.

Anti-Bacterial Agents↗

Susceptibility of Acinetobacter calcoaceticus to antimicrobial drugs, alone and combined, with and without defibrinated human blood.

Twenty-five clinical isolates of Acinetobacter calcoaceticus were examined for susceptibility to 14 antimicrobial drugs. In terms of inhibitory and bactericidal activities, imipenem and polymyxin B were most active, followed by amikacin and ceftazidime. Four isolates were resistant against fluoroquinolones (ciprofloxacin, norfloxacin, ofloxacin). The isolates varied in susceptibility to aztreonam, cefotaxime, cotrimoxazole, gentamicin, mezlocillin, netilmicin and piperacillin. Fresh defibrinated human blood from 3 donors revealed similar killing kinetics against 8 selected isolates. In time-kill curve experiments, human blood enhanced the activity of amikacin more than that of ceftazidime, ciprofloxacin and imipenem against A. calcoaceticus. The combinations of amikacin + imipenem and amikacin + ceftazidime in the presence of human blood were effective against this microorganism. Human blood combined with ciprofloxacin + imipenem was more effective than blood with added ceftazidime + ciprofloxacin.

Acinetobacter↗

Comparison of inhibitory and bactericidal activity of antipseudomonal antibiotics against Pseudomonas aeruginosa isolates from cystic fibrosis patients.

Using a broth microtiter dilution method, the minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC) of so-called antipseudomonal antibiotics were determined against 79 Pseudomonas aeruginosa isolates from cystic fibrosis patients. On the basis of the MIC values and using DIN breakpoints, the percentual susceptibilities led to the following rank order: imipenem (91%), ciprofloxacin (90%), tobramycin (87%), amikacin (87%), ceftazidime (82%), cefsulodin (76%), piperacillin (71%), azlocillin (62%), followed by gentamicin, ceftriaxone, mezlocillin, netilmicin, and cefotaxime (less than 50%). However, evaluating MBC values according to DIN breakpoints, only ciprofloxacin (82%), tobramycin (77%), amikacin (58%), and imipenem (57%) showed a pronounced antipseudomonal effectiveness. The data indicate that MBC determinations are necessary to evaluate the antibiotic susceptibility of P. aeruginosa rather than MIC determinations, at least in patients with impaired defence mechanisms which require bactericidal therapy.

Amikacin↗

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

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

Aminoglycosides↗

Nephrotoxicity of aminoglycosides, polypeptides and cephalosporins in cancer patients.

The nephrotoxicity of various combinations of antibiotics--aminoglycosides, cephalosporins, vancomycin, amphotericin B--in 171 oncologic patients is described. The most nephrotoxic combination seems to be cefotaxime plus gentamicin, ceftriaxone plus amikacin and amphotericin B with cephalosporin, vancomycin or aminoglycoside. Less toxic was netilmicin with penicillin or cephalosporin, and vancomycin.

Aminoglycosides↗

Antibiotic susceptibility tests with fastidious and nonfastidious bacterial reference strains: effects of aerobic versus hypercapnic incubation.

Representative antimicrobial drugs were examined under aerobic and hypercapnic (3 and 5% v/v CO2) incubation with the Bauer-Kirby agar disk diffusion, a broth microdilution method, and the agar dilution procedure against nonfastidious, standard ATCC quality control strains and against two beta-hemolytic streptococcal, two pneumococcal, and three Haemophilus influenzae ATCC strains. It was found that an atmosphere of 3-5% CO2 merely antagonized amikacin, gentamicin, and netilmicin; the activity of penicillin G was antagonized only against Staphylococcus aureus ATCC 29213 in broth media, but not against any of the other strains. The activity of teicoplanin, and less so that of vancomycin, was enhanced only against S. aureus strain ATCC 25923, but not against the other strains. It was concluded that susceptibility tests, excluding aminoglycoside antibiotics, of beta-hemolytic streptococci, pneumococci, and H. influenzae and H. parainfluenzae should be incubated under 3% (candle jar or incubator) or 5% CO2 (incubator) so as to ensure optimal growth of capnephilic strains and thus avoid potentially misleading large inhibition zones of deceptively low minimal inhibitory concentrations.

Aerobiosis↗

Transferable amikacin resistance in gram-negative bacterial isolates.

Seven amikacin-resistant strains of Enterobacteriaceae isolated in Slovakia and Germany were included in this study. The strains were also resistant in vitro to high levels of gentamicin, tobramycin, netilmicin and isepamicin. Phosphocellulose paper binding assays indicated that resistance to aminoglycosides was due to synthesis of aminoglycoside acetyltransferase AAC(6')-I a mechanism until now only identified in staphylococci and streptococci. This mechanism of aminoglycoside resistance has also been found in two isolates of Klebsiella pneumoniae from Germany. The substrate profile suggested that in addition to AAC(6')-I and APH(2"), several strains also produced AAC(3)-II. Aminoglycoside resistance was found to be transferable to Escherichia coli 3110 rifr in all isolates, and R plasmids of 36-45 MD were detected in donor and transconjugant strains. All isolated plasmids from transconjugants encoded resistance to aminoglycosides by genes encoding the enzymes AAC(6')-I and APH(2").

Acetyltransferases↗

Antibiotic sensitivity of recent clinical isolates from patients with ocular infections.

We examined the status of bacterial infection and drug sensitivity in patients who consulted the Ocular Infection Clinic of Niigata University between 1992 and 1995. Overall, 850 strains were detected. Gram-positive cocci were the most frequent (380 strains, 44.7%). We detected 63 strains of gram-negative bacilli (7.4%), 207 strains of anaerobic bacteria (24.4%) and 18 strains of fungi (2.1%). Among gram-positive cocci, coagulase-negative staphylococci (CNS) were the most prevalent (52.6%). Of gram-negative bacilli, glucose-nonfermenting gram-negative rods (GNF-GNR) were the most prevalent (27.0%). The detection rate of methicillin-resistant Staphylococcus aureus (MRSA) was 27.0% (20/74 strains). The detection rate of methicillin-resistant CNS was 6.8% (19/147 strains). Concerning drug sensitivity, most of the 54 strains of methicillin-sensitive S. aureus showed low sensitivity to penicillin G (PCG), ampicillin (ABPC) and erythromycin (EM). Most strains of MRSA showed low sensitivity to PCG, ABPC, cefazolin, flomoxef, imipenem (IPM), ofloxacin (OFLX), EM and clindamycin (CLDM), but high sensitivity to netilmicin, arbekacin (ABK), minocycline (MINO) and vancomycin. The drug sensitivity of CNS was similar to that of S. aureus. Of 27 strains of Streptococcus pneumoniae, 4 (14.8%) were resistant to PCG. Five strains of Pseudomonas aeruginosa showed high sensitivity to piperacillin, ceftazidime, IPM, tobramycin, ABK and OFLX. Most strains of other GNF-GNR showed high sensitivity to IPM, MINO and OFLX. Most strains of anaerobic bacteria showed high sensitivity to IPM, MINO and CLDM.

Anti-Bacterial Agents↗

Pharmacokinetics of aminoglycosides in subjects with normal and impaired renal function.

Since aminoglycosides are antibiotics almost exclusively eliminated by the kidneys, their pharmacokinetic study in normal subjects and in uraemic patients is essential to establish dosage schedules adapted to various degrees of renal impairment. Many studies have been recently reported, particularly with regard to the newly developed desoxystreptamine aminoglycoside antibiotics. The present paper is a compilation of our own results and a review of the literature concerning Streptomycin, Kanamycin and its semi-synthetic derivation, Amikacin or BB-K8, Gentamicin, Tobramycin, Lividomycin, Sisomicin and its semi-synthetic derivation, Netilmicin.

Aminoglycosides↗