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PubMed2006

Prevalence of aminoglycoside-modifying enzymes genes among isolates of Enterococcus faecalis and Enterococcus faecium in Iran.

Disks containing 120 microg of gentamicin were used to detect high-level gentamicin-resistant phenotype (HLGR) among isolates of Enterococcus faecalis (n = 79) and E. faecium (n = 35). These isolates were collected from three hospitals in Tehran during 2002-2004. The macrobroth dilution assay was then used to determine the minimum inhibitory concentration (MIC) of gentamicin. The susceptibility of isolates against amikacin, netilmicin, tobramycin, and kanamycin were also determined by Kirby-Bauer method. All isolates were subjected to polymerase chain reaction (PCR) assays targeting aminoglycoside modifying enzyme (AMEs) genes including aac(6 ')-aph(2 "), aph(2 ")-Ib, aph(2 ")-Ic, aph(2 ")-Ia, aph(2 ")-Id, aph(3 ')-IIIa, and ant(4 ')-Ia. Fifty-nine isolates (52%) showed HLGR phenotype. All isolates with HLGR phenotype and those showing 64 < MIC < 500 microg/ml contained aac(6 ')-aph(2 "). The aph(3 ')-IIIa was found in 61% of the isolates with HLGR phenotypes and in 65% of isolates with MIC < 500. Coexistence of aac(6 ')-aph(2 ") and aph(3 ')-IIIa gene among HLGR isolates of E. faecalis and E. faecium were 60% and 65%, respectively. The gene aph(2 ")-Ic was amplified in two isolates of E. faecium. The results of PCR for aph(2 ")-Id, ant(4 ')-Ia and aph(2 ")-Ib genes were negative. The aac(6 ')-aph(2 ") was the most frequent gene encoding resistance to gentamicin and other aminoglycosides followed by aph(3 ')-IIIa. Isolates lacking these genes were susceptible to all aminoglyocosides tested in this study.

Aminoglycosides↗
PubMed1981

Comparison of minimum inhibitory concentration values determined by three antimicrobic dilution methods for Pseudomonas aeruginosa.

This investigation compares minimum inhibitory concentration measurements by three antimicrobic dilution methods for Pseudomonas aeruginosa versus seven antimicrobics. Minimum inhibitory concentrations were measured for 650 P. aeruginosa clinical isolates and for repeated tests with P. aeruginosa ATCC 27853 versus gentamicin, tobramycin, amikacin, netilmicin, sisomicin, carbenicillin, and ticarcillin, using the macro-broth, micro-broth, and agar dilution methods. For all antimicrobics, it was found that the micro-broth and agar dilution methods produced comparable minimum inhibitory concentration measurements, which were found to lie 1 to 2 double dilution steps below those determined by the macro-broth method. Acceptably replicability was found for both the macro-broth and the agar dilution methods. The micro-broth method showed less replicability, with 4.7% of minimum inhibitory concentration values lying +/- 2 or more double dilution steps from the modal value. It is important to recognize such differences if micro-broth or agar dilution methods are substituted for the macro-broth method.

Aminoglycosides↗
PubMed1984

Aminoglycoside resistance in Pseudomonas aeruginosa isolated from cystic fibrosis patients.

The authors studied 30 gentamicin-resistant and 17 gentamicin-sensitive strains of Pseudomonas aeruginosa isolated from respiratory cultures of patients with cystic fibrosis from five United States cities for the presence of plasmids, cross-resistance to other aminoglycosides, and the production of aminoglycoside-modifying enzymes. Four of 30 resistant strains and 3 of 17 sensitive strains contained one or more plasmids. Aminoglycoside cross-resistance to tobramycin, amikacin, and netilmicin was seen in 21 of 30 gentamicin-resistant strains. Seven strains that had low-level gentamicin resistance (minimum inhibitory concentrations [MIC] = 8-32 micrograms/mL) were sensitive to one or more of the other three aminoglycosides. Two strains with high-level gentamicin resistance (MIC greater than or equal to 128 micrograms/mL) were sensitive to amikacin. These two strains, each containing three plasmids, were the only isolates of nine tested that produced an aminoglycoside-modifying enzyme with activity against gentamicin. None of the plasmids was transferable by conjugation. Four strains, three of which contained one or more plasmids, produced an aminoglycoside 3'-0-phosphotransferase II. The authors propose that the mechanism of gentamicin resistance in P. aeruginosa from patients with cystic fibrosis is not commonly plasmid-mediated and likely is due to membrane impermeability to aminoglycosides.

Aminoglycosides↗
PubMed1992

Resistance of enterococci to aminoglycosides and glycopeptides.

High-level resistance to aminoglycosides in enterococci often is mediated by aminoglycoside-modifying enzymes, and the corresponding genes generally are located on self-transferable plasmids. These enzymes are similar to those in staphylococci but differ from the modifying enzymes of gram-negative bacteria. Three classes of enzymes are distinguished, depending upon the reaction catalyzed. All but amikacin and netilmicin confer high-level resistance to the antibiotics that are modified in vitro. However, the synergistic activity of these last two antibiotics in combination with beta-lactam agents can be suppressed, as has always been found in relation to high-level resistance to the aminoglycosides. Acquisition of glycopeptide resistance by enterococci recently was reported. Strains of two phenotypes have been distinguished: those that are resistant to high levels of vancomycin and teicoplanin and those that are inducibly resistant to low levels of vancomycin and susceptible to teicoplanin. In strains of Enterococcus faecium highly resistant to glycopeptides, we have characterized plasmids ranging from 34 to 40 kilobases that are often self-transferable to other gram-positive organisms. The resistance gene vanA has been cloned, and its nucleotide sequence has been determined. Hybridization experiments showed that this resistance determinant is present in all of our enterococcal strains that are highly resistant to glycopeptides. The vanA gene is part of a cluster of plasmid genes responsible for synthesis of peptidoglycan precursors containing a depsipeptide instead of the usual D-alanyl-D-alanine terminus. Reduced affinity of glycopeptides to these precursors confers resistance to the antibiotics.

Aminoglycosides↗
PubMed1992

Antibiotic susceptibility profiles of 941 gram-negative bacteria isolated from septicemic patients throughout Canada. The Canadian Study Group.

The choice of antimicrobial therapy for the treatment of bacteremia is often empirical and based on the knowledge of antibiotic susceptibility profiles of the most common bacteria causing such infections. It therefore is crucial to survey the susceptibility of bacteria causing sepsis. This study examines the susceptibility profiles of 941 gram-negative bacteria, isolated from septic patients in 10 Canadian hospitals, to 28 antimicrobial agents. Among the isolates, 30 different species were represented; Escherichia coli dominated, representing 52.5% of isolates. More than 50% of all bacteria were resistant to ampicillin. Only 67% of the E. coli isolates were susceptible to ampicillin, while 30% of all strains were resistant to ticarcillin. Of the cephalosporins, ceftazidime and cefoperazone/sulbactam were the agents to which isolates were the most susceptible (90%). Only 51% of the E. coli strains were susceptible to cephalothin, while 91% were still susceptible to cefazolin. A total of 93% and 98% of the strains were susceptible to aztreonam and imipenem, respectively. Aminoglycosides were highly active against most isolates, in general in the following order: netilmicin greater than tobramycin greater than gentamicin greater than amikacin. Tobramycin was the most active against Pseudomonas aeruginosa. Nearly all isolates were susceptible to the quinolones. Tolerance (MBC/MIC ratio, greater than or equal to 32) was rarely observed. This survey of the susceptibility of gram-negative bacteria causing sepsis provides valuable information for implementing the chemotherapy for gram-negative septicemia and demonstrates that several older and newer agents, alone or in combination, can be used as adequate initial therapy for gram-negative sepsis in Canada.

Anti-Bacterial Agents↗
PubMedDate not supplied

Neonatal meningitis due to Streptococcus mitis.

A baby girl became ill 2 days after a normal delivery. Streptococcus mitis was isolated from the cerebrospinal fluid, and she recovered uneventfully on treatment with penicillin and, for the first 2 days, netilmicin. The organism was penicillin-tolerant in vitro. Non-groupable alpha-hemolytic streptococci are an uncommon cause of meningitis; three cases have been ascribed to S. mitis.

Adult↗
PubMed1995

Drugs of choice for the treatment of uncomplicated gonococcal infections.

Resistance of Neisseria gonorrhoeae to antimicrobial agents continues to spread and intensify. Choosing an antimicrobial regimen requires knowledge of the comparative efficacy of candidate regimens, as delineated in properly conducted clinical trials; their activity against N. gonorrhoeae in vitro; and their pharmacokinetics and toxicity. We tabulated the results of trials of single-dose antimicrobial therapy for uncomplicated gonococcal infection published after 1980. Thirty regimens comprising 21 antimicrobial drugs have been shown to be highly effective for rectal and urogenital infections; the agents involved are cefixime, cefodizime, cefotaxime, cefoxitin, ceftizoxime, ceftriaxone, cefuroxime, cefuroxime axetil, ciprofloxacin, fleroxacin, norfloxacin, ofloxacin, pefloxacin, temafloxacin, azithromycin, aztreonam, netilmicin, rifampin plus erythromycin stearate, sisomicin, and spectinomycin. Few regimens have been shown to be highly effective against pharyngeal infections. Among those antimicrobial agents available for the treatment of uncomplicated gonococcal infections in the United States, ceftriaxone (125 mg), cefixime (400 mg), ciprofloxacin (500 mg), and ofloxacin (400 mg) appear to offer the best balance of proven efficacy and safety.

Anti-Bacterial Agents↗
PubMed1996

Clinical significance of extraintestinal Hafnia alvei isolates from 61 patients and review of the literature.

Hafnia alvei is a gram-negative bacterium that is rarely isolated from human specimens and is rarely considered to be pathogenic. It has been associated with gastroenteritis, meningitis, bacteremia, pneumonia, nosocomial wound infections, endophthalmitis, and a buttock abscess. We studied 80 H. alvei isolates recovered from 61 patients within a period of 30 months. H. alvei was cultured from sites that included the respiratory tract (n = 38), the gastrointestinal tract (n = 16), and the urogenital tract (n = 12); the organism was found in blood cultures (n = 8), on central venous catheters (n = 3), and on the skin (n = 3). Only 25% of H. alvei isolates were recovered in pure cultures. Fifty-seven (93.4%) of the patients had an underlying illness. H. alvei proved to be the etiologic agent in two episodes of septicemia and in one episode of peritonitis and was probably responsible for septicemia in two other patients and pneumonia in one. All six of these patients recovered after receiving antibiotic treatment and/or standard surgical treatment, when needed. Three of these infections were nosocomial, and three were community acquired. Of the strains of H. alvei tested in our study, 100% were susceptible to netilmicin, ciprofloxacin, and imipenem; 92% were susceptible to piperacillin; 90% were susceptible to co-trimoxazole; and 88% were susceptible to ceftriaxone and ceftazidime. In this study, we found H. alvei to be a rare significant etiologic agent of nosocomial and community-acquired infections.

Adolescent↗
PubMedDate not supplied

Current problems in the treatment of infective endocarditis due to Pseudomonas aeruginosa.

Mortality from pseudomonas infective endocarditis remains high despite optimal use of available antibacterial agents. Infection of the tricuspid valve is subacute, but involvement of the mitral or aortic valve precipitates more serious disease. Most valvular infections are due to a single pseudomonad immunotype, but 20% of cases are mixed infections. Antimicrobial susceptibility tests and tests of synergy by beta-lactam and aminoglycoside antibiotics in combination were performed on 30 isolates of Pseudomonas aeruginosa. Azlocillin was the most effective beta-lactam in combination with an aminoglycoside; MKO 787 was least effective. Among the aminoglycosides tested, netilmicin was the most effective. Medical treatment combined with valvulectomy (without valve replacement) is now standard treatment for refractory right-sided endocarditis at this medical center. A high dose of aminoglycoside in combination with a beta-lactam has proved efficacious. For left-sided infection, immediate valve replacement accompanied by a six-week course of the high dose-combined drug regimen is recommended. Newer beta-lactam antibiotics, such as piperacillin, may be limited in usefulness due to beta-lactamase inactivation.

Adolescent↗
PubMed1984

Bactericidal activity of five combinations of penicillin G with aminoglycosides against Streptococcus faecium.

Combinations of penicillin G and five aminoglycosides were tested against 7 strains of S. faecium. For all the strains that had a low-level of resistance to streptomycin, the combination of penicillin G with streptomycin was synergistic. Penicillin combined with either kanamycin or netilmicin was ineffective against all strains. The combination of penicillin and amikacin was synergistic against only one of the aminoglycoside-susceptible strains and ineffective against all the other strains. Penicillin G with gentamicin was the only combination synergistic against all strains. The clinical implications of these findings for the treatment of bacterial endocarditis caused by S. faecium are discussed.

Aminoglycosides↗
PubMed1983

Synergy of azlocillin with aminoglycosides.

The combination of azlocillin and the aminoglycosides amikacin, gentamicin, netilmicin, sisomicin, and tobramycin was synergistic. The FIC index was less than or equal to 0.5 for 28 to 42% of Pseudomonas aeruginosa isolates tested and with an additive FIC index greater than 0.5-1 for 53 to 63% of the isolates. Antagonism was not encountered. Isolates resistant to azlocillin (MIC greater than 100 mg/l) were more often synergistically inhibited by the combination of azlocillin and an aminoglycoside. The concentrations of antibiotics that synergistically inhibited Pseudomonas were those readily achieved in man. The combination of azlocillin and aminoglycosides prevented regrowth of isolates that grew after initial suppression by the antibiotics alone.

Aminoglycosides↗
PubMed1984

Species identification and antibiotic sensitivity of coagulase-negative staphylococci from CAPD peritonitis.

Forty-three strains of coagulase-negative staphylococci were obtained from dialysis effluent during 41 episodes of CAPD peritonitis. Eighty per cent of these were found to be Staphylococcus epidermidis but several other species also occurred. A recurrent infection lasting 15 weeks was caused by Staph. haemolyticus. Multiple antibiotic resistance was found to be common. Of 13 antibiotics tested, only vancomycin was active against all strains although most strains were also sensitive to rifampicin, netilmicin and cefamandole. Vancomycin was chosen for the initial treatment of CAPD peritonitis caused by coagulase-negative staphylococci and eradicated the organism in 29 of 30 episodes.

Anti-Bacterial Agents↗
PubMed1984

Dissociation of maximum concentration of kanamycin in plasma and perilymph from ototoxic effect.

Kanamycin was administered in total daily doses of 0 (vehicle), 100, 200 or 300 mg/kg to different groups of guinea pigs for two weeks. These total daily doses were administered according to three different dosing schedules, either as a single injection given once a day, divided into two equal doses and given twice a day, or divided into four equal doses and administered four times a day. It was found that the magnitude of the ototoxicity resulting from kanamycin administration was related to the total daily dose alone and not the dosing schedule. This lack of relationship between the dosing schedule and the magnitude of the ototoxicity due to kanamycin is the reverse of that reported for the nephrotoxicity resulting from gentamicin, tobramycin and netilmicin.

Animals↗
PubMed1985

The use of bacteria producing the aminoglycoside inactivating enzyme ANT-(2") in an in-vitro model.

A series of transconjugants of Escherichia coli W3110 containing different plasmids coding for the aminoglycoside inactivating enzyme ANT-(2") were tested in an in-vitro model simulating the concentration time curves of aminoglycosides after intramuscular administration of 80 or 120 mg. There was good correlation of the MIC, which ranged from 2 to 32 mg/l, with the killing ability of the drugs. A second dose had no or only little effect on ANT-(2") producing strains. All strains, although of 'intermediate' sensitivity were found to be resistant in the in-vitro model. Only netilmicin could eliminate some of the strains but its activity on ANT-(2")-positive strains was not as good as on ANT-(2")-negative ones.

Aminoglycosides↗
PubMed1986

Sensitivity patterns of coagulase-negative staphylococci from neonates.

Coagulase-negative staphylococci from neonates on two special care baby units were collected and the sensitivity patterns to 18 antibiotics were compared. The two units had different antibiotic policies and this correlated with different sensitivity profiles for the isolates. Netilmicin was shown to be the most active aminoglycoside and cefamandole the most active cephalosporin.

Aminoglycosides↗
PubMed1986

Antibacterial activity of enoxacin: comparison with aminoglycosides, beta-lactams and other antimicrobial agents.

The activity of enoxacin, a new quinolone carboxylic acid, was evaluated against 3014 clinical isolates of Enterobacteriaceae, Pseudomonas and other non-fermenters and Staphylococcus aureus. Comparison was made with gentamicin, tobramycin, amikacin, netilmicin, ampicillin, piperacillin, carbenicillin, ticarcillin, ticarcillin plus clavulanic acid, trimethoprim, cotrimoxazole and erythromycin. In general enoxacin was the most active compound and resistance was only rarely encountered.

Aminoglycosides↗
PubMed1986

Timentin (ticarcillin and clavulanic acid) in combination with aminoglycosides in the treatment of febrile episodes in neutropenic children.

Timentin (ticarcillin + clavulanic acid) combined with an aminoglycoside usually netilmicin, was given to 33 children with neutropenic haematological malignancies. The combination of Timentin and aminoglycoside was effective treatment in 27 (87%) of 31 febrile episodes. There were four failures and three results which could not be interpreted. Bacteriological investigations were positive in 13 patients, three strains were resistant to ticarcillin but all were sensitive to Timentin. Clinical success, based upon reduction of fever within 48 h of treatment, was identical whether an organism was isolated or not. The combination of Timentin plus aminoglycoside was very successful and represents one of the best combinations available for empirical treatment for febrile neutropenic children.

Adolescent↗
PubMed1986

Susceptibility of Pseudomonas aeruginosa strains isolated from hospitalized children.

Pseudomonas aeruginosa strains, 1285 in total, were isolated from hospitalized children in the period 1981-1984. Serotypes 011 and 06 and nontypable strains were the most frequently identified. 44.6% of serotype 011 strains and between 12.4 and 37.7% of other serotypes were resistant to gentamicin, or carbenicillin, or both agents. The aminoglycosides with the highest activity against P. aeruginosa isolates were amikacin and netilmicin. Among the seven beta-lactam antibiotics tested the most active were cefsulodin, piperacillin and azlocillin.

Aminoglycosides↗