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PubMedDate not supplied

Vestibulo-ocular reflex (VOR) in guinea pigs. Impairment induced by aminoglycoside antibiotics.

The vestibulo-ocular reflexes (VORs) were studied in guinea pigs receiving daily administration of aminoglycoside antibiotics. The vestibular epithelia were also examined by scanning electron microscope technique (SEM). The treatment with aminoglycosides led to varying degrees of VORs according to (i) the type of aminoglycoside drug; (ii) the duration of the treatment and, (iii) the sensitivity of the various vestibular receptors. Gentamicin caused an earlier and severe reduction of the VOR gain. Dibekacin also caused evident damage, but the onset of its action was delayed. Both drugs affected mainly the vertical responses. Tobramycin and netilmicin altered the VORs slightly. Histological examination revealed damage to the sensory epithelia corresponding to the observed VOR impairments.

Aminoglycosides↗
PubMed1988

Aminoglycoside resistance patterns in Turkey.

Resistance of gram-negative aerobic bacteria to aminoglycoside antibiotics differs by region and country. It is known that 54% of gram-negative bacilli in Turkey are resistant to gentamicin, 32% to netilmicin, 35% to tobramycin, and only 0.9% to amikacin. Resistance to these antibiotics is generally caused by aminoglycoside-modifying enzymes. The resistance mechanisms of 300 aminoglycoside-resistant gram-negative bacteria were evaluated by determination of susceptibility to selected aminoglycosides. Comparison of strains isolated from community acquired infections and hospital acquired infections was made. Of the strains from community, 45.4% had an aminoglycoside resistance pattern indicative of 2''-adenyltransferase [ANT(2'')]. This was found in 44.4% of the hospital isolates. In both groups the second common enzyme was the 3-acetyltransferase [AAC(3)-II], in 20.8% and 23.3% respectively. Overall, most strains had an aminoglycoside resistance pattern indicative of ANT(2''), followed by AAC(3)-II and AAC(3)-I. Among bacteria tested, AAC(3)-II was the most common enzyme in Pseudomonas aeruginosa. The results of this study suggest that local antibiotic prescribing patterns play an important role in regional resistance mechanisms.

Acetyltransferases↗
PubMed1990

Neonatal sepsis due to Streptococcus pneumoniae.

A 20-year-old primigravida in the 33rd week of gestation was delivered of a girl weighing 1,790 g 23 h after spontaneous rupture of the membranes. 13 h after birth, the child showed signs of shock. Cultures of blood, conjunctiva and nasopharyngeal aspirate grew Streptococcus pneumoniae of serotype 11. Cultures from the mother's cervix and from the placenta and membranes also grew S. pneumoniae of the same serotype. The infant responded well to ampicillin and netilmicin. The early-onset pneumococcal septicemic cases reported over the last 20 years are reviewed.

Adult↗
PubMedDate not supplied

Doxorubicin reversibly decreases the antithrombogenicity of heparin immobilized on central venous catheters.

This is an in vitro study of the effects of doxorubicin on heparin immobilized on polyvinyl chloride (PVC) tubing. Doxorubicin contains an amino group that binds up to 16 heparin molecules, forming insoluble complexes if they are added to the same infusion. Three systems were tested: doxorubicin in perfusing blood, cerebrospinal fluid, and 0.9% sodium chloride (NaCl). The antithrombogenicity of immobilized heparin is impaired on exposure to doxorubicin. However, the reaction is reversible provided the PVC tubing system is thoroughly washed. Heparinized tubing perfused for 12 hours in blood with doxorubicin (0.027 mg/mL) decreased the activity of the immobilized heparin to 6.0% compared with 43% of that exposed to blood only. Exposure to doxorubicin (0.27 mg/mL) for 15 minutes in NaCl decreased the activity to 3% compared with that of NaCl only. Continuous washing for 10 minutes (8 mL/min) resulted in regained activity. This indicated a reversible reaction between immobilized heparin and doxorubicin. Cyclophosphamide, netilmicin, and gentamicin did not affect the antithrombogenicity of heparin in any solution.

Biocompatible Materials↗
PubMed1987

Antibiotic penetration into the infected knee. A rabbit experiment.

We investigated the diffusion of penicillin-G, cloxacillin, clindamycin, and netilmicin into synovial fluid and membrane in rabbits. Purulent arthritis was induced in the right knee of each rabbit by inoculation of Staphylococcus aureus phage type 3C, whereas sterile saline was injected into the left knee to serve as a control. Two days later, concentrations of antibiotics were determined in serum, synovial fluid, and membrane after an intramuscular single dose. All four drugs diffused readily into infected joints, whereas the corresponding concentrations in the normal joints were 2-3 times lower. Clindamycin showed the highest intraarticular penetration, cloxacillin the lowest. The lower penetration of cloxacillin corresponded to its higher protein binding in rabbit serum. Considering the sufficient local concentrations achieved, parenteral treatment obviates the need for local instillation of these antibiotics.

Animals↗
PubMed1999

Adsorption and release of antibiotics from morselized cancellous bone. In vitro studies of 8 antibiotics.

We studied the basic release patterns of antibiotics from cancellous bone in vitro. Antibiotic-impregnated bone was compressed into a wire-mesh cylinder and the release of antibiotic was assessed by two different in vitro methods: agar diffusion and broth elution. The zones of inhibition were measured on seeded agar and the amounts of antibiotics released in elution tubes were assessed by a bioassay. The study continued for 21 days with daily transfer of the cylinders. The results indicated that benzylpenicillin, dicloxacillin, cephalotin, netilmicin, clindamycin, vancomycin, ciprofloxacin and rifampicin were adsorbed to cancellous bone in vitro. Compared to broth elution, agar diffusion showed a prolonged period of release, owing to the small amounts of antibiotic leaking out of the cylinder into the agar. The betalactams had antibacterial activity in broth for a shorter time than the other antibiotics. The release patterns of the betalactams were similar, in spite of their differences in thermal stability. Only rifampicin showed a concentration higher than MIC for longer than 21 days.

Adsorption↗
PubMedDate not supplied

[Frequency and susceptibility to antibiotics of Neisseria gonorrhoeae at Lomé].

A cross-sectional study was carried out by the bacteriology laboratory of the Lome-Tokoin University Hospital, to determine the frequency of gonorrhea in patients providing vaginal or urethral samples, and to investigate the susceptibility of N. gonorrhoeae to antibiotics. The samples were treated according to classic bacteriological methods and the disk diffusion tests were used to investigate antibiotic susceptibility. The samples were taken from 420 patients, 246 of whom were male (26.86% ¿NdT: d'où vient ce chiffre??, 58.33% si 420 patients, 61.19% si 402 patients¿) and 156 of whom were female (37.14% ¿NdT: plutôt 38.8% si 402 patients¿) ¿NdT: et le reste?? Il me semble que c'est plutôt 402 patients en total (= 246 + 156). Sinon il y a 18 patients qui ne sont ni male ni femelle?!¿. N. gonorrhoeae was isolated from 88 patients, giving a prevalence of 20.95% ¿NdT: ou 21.89% si 402 patients¿. We isolated strains of the bacterium from 76 men (25.78% ¿NdT: incorrect, 30. 89%¿ and 12 women (7.69%). Ciprofloxacin, ofloxacin and netilmicin were the most effective antibiotics. The cyclins, cotrimoxazole and penicillin were less effective.

Adolescent↗
PubMed2000

[In vitro interaction of piperacillin and imipenem/cilastatin combined with aminoglycosides against Pseudomonas aeruginosa].

The in vitro interactions of piperacillin (PIPC) and imipenem/cilastatin (IPM/CS) combined with 5 kinds of aminoglycosides (gentamicin, tobramycin, amikacin (AMK), isepamicin and netilmicin) were investigated against IPM/CS-susceptible (MIC of IPM/CS was < or = 3.13 micrograms/ml) and IPM/CS-resistant (MIC of IPM/CS was > or = 12.5 micrograms/ml) Pseudomonas aeruginosa. The following results were obtained. 1. In the checkerboard dilution studies, the combinations of PIPC with aminoglycosides showed synergistic effect for more than 50% of the each 54 strains of IPM/CS-susceptible and IPM/CS-resistant P. aeruginosa. The synergistic/additive effects of PIPC with aminoglycosides were demonstrated for all tested strains. 2. In the checkerboard dilution studies, the combinations of IPM/CS with aminoglycosides showed no antagonism against any strains. The synergistic effects of IPM/CS with aminoglycosides were demonstrated for 0 to 14.8%, and these values were smaller than the combinations of PIPC with aminoglycosides. 3. Corresponding to the results of checkerboard dilution studies, the combination of PIPC with AMK was more effective than the combination of IPM/CS with AMK on the killing curve for IPM-resistant P. aeruginosa. In conclusion, PIPC showed the synergistic effects in combinations with aminoglycosides against IPM/CS-resistant P. aeruginosa. These results suggest that the combination therapies of PIPC with aminoglycosides are useful for the clinical treatment of serious infections due to P. aeruginosa.

Amikacin↗
PubMed2002

Resistance of Klebsiella pneumoniae strains producing and not producing ESBL (extended-spectrum beta-lactamase) type enzymes to selected non-beta-lactam antibiotics.

BACKGROUND: Bacteria of the Klebsiella genus may cause numerous infections in human, which are often treated with beta-lactam antibiotics. The fundamental mechanism of Klebsiella resistance to penicillins or cephalosporins involves the production of enzymes--extended-spectrum beta-lactamases (ESBLs). Because of resistance of many Klebsiella spp. strains to beta-lactams, alternative antibiotic therapy can make use of aminoglycosides and quinolones. MATERIAL/METHODS: The study analyzed the prevalence of ESBL -type enzymes among 256 Klebsiella pneumoniae strains isolated from various clinical materials collected from patients hospitalized between 1997 and 2000. ESBLs were detected by double-disk synergy test (DDST). The prevalence of strains resistant to selected aminoglycosides (gentamicin, amikacin, netilmicin) and quinolones (ciprofloxacin, norfloxacin, nalidixic acid) in the particular years was analyzed. Drug sensitivity was determined by disk-diffusion method according to the recommendations of the National Reference Center for Microbial Drug Sensitivity. RESULTS: During the analyzed time interval, a significant increase of the number of K. pneumoniae ESBL(+) strains was noted: in 1997 - 16.5% (14/85) and in 2000 - 40.4% (22/54) (p<0.001). Among the ESBL(+) strains, an increase of the number of strains resistant to the tested antibiotics, except for nalidixic acid, was demonstrated CONCLUSIONS: A statistically significant increase of multidrug-resistant K. pneumoniae strains, including strains producing ESBLs, was demonstrated in the analyzed material.

Amikacin↗
PubMed2002

[Antibacterial activities and PK/PD parameters of aminoglycosides against recent clinical isolates of gram-negative rods].

We examined antibacterial activities and PK/PD parameters of six kinds of aminoglycosides against seven bacterial species of clinical isolates in 2001. Aminoglycoseides examined were gentamicin (GM), dibekacin (DKB), tobramycin (TOB), amikacin (AMK), netilmicin (NTL), and isepamicin (ISP), and bacterial isolates used were each 50 strains of Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii, Proteus spp., Serratia marcescens and Pseudomonas aeruginosa. All aminoglycosides showed good activities with low MICs against 6 species of Enterobacteriacea except S. marcescens. Eight strains (3.2%) among them were resistant to one or more aminoglycosides. Resistance to multiple aminoglycosides were detected in 16 strains (32%) of S. marcescens, among which 13 strains were resistant to AMK but susceptible to ISP. Three (6%) strains of P. aeruginosa were resistant to multiple drugs, one of which was resistant to all six aminoglycosides, and others were moderately susceptible to AMK and ISP, and susceptible to GM, AMK and ISP. Using a ratio of peak serum concentration to MIC90 (Cmax/MIC90) or a ratio of area under the curve to MIC90 (AUC/MIC90) as a pharmacokinetic and pharmacodynamic (PK/PD) parameter, we estimated the efficacy of the drug. An excellent effect of ISP, which was injected intramuscularly or intravenously at a dose of 400 mg, was expected for strains of Enterobacteriacea except S. marcescens. The Cmax/MIC90 ratios for S. marcescens were comparably higher in GM and ISP and that for P. aeruginosa were rather high in TOB when compared to other aminoglycosides. Another PK/PD parameter, AUC/MIC90 ratio, was high enough in NTL and ISP for Enterobacteriacea, suggesting good efficacy of these drugs. The (AUC/MIC90) ratios for S. marcescens were comparably high in GM and ISP, and that for P. aeruginosa were high in TOB, DKB, and ISP.

Amikacin↗
PubMed1992

Antibiotic prophylaxis and prosthetic valve endocarditis.

Early onset prosthetic valve endocarditis is one of the most lethal complications after valve replacement. During the first year of operation of our new cardiac surgical program, we observed 10 cases of prosthetic valve endocarditis, the majority being caused by staphylococci, making an incidence of 10.6%. Subsequent investigations uncovered a very high prevalence of methicillin-resistant strains which led to a radical change in the antibiotic prophylaxis, from a cephalosporin-based protocol to a two drug regime of vancomycin and netilmicin. There were no cases of prosthetic infection among the 138 patients operated on in the one year period following the institution of this protocol. Because there were no other changes, either in the types of prostheses used or the techniques of implantation, the eradication of prosthetic valve endocarditis can be related only to this alteration in the prophylaxis. Therefore, we may conclude that the inter-institutional transfer of protocols is not adequate before a thorough investigation of the prevalent hospital pathogens and their sensitivity to antibiotics is carried out. We have not registered resistances to vancomycin and this drug remains the most important antimicrobial agent, both in the prophylaxis and in the treatment of prosthetic valve endocarditis.

Adult↗
PubMed2004

[Sensitivity of MRSA isolated in our hospital to various antibacterial agents: changes over 5 years].

Among methicillin resistant Staphylococcus aureus (MRSA) strains isolated from clinical specimens during 5 years period from 1998 through 2002 in Cancer Institute Hospital, Japanese Foundation for Cancer Research, a total of 100 strains, one per patient, were successively selected each year, and their sensitivity to various antibacterial agents was measured to assess changes over five years in their sensitivity to these drugs. The following results were obtained. 1. Little or no change was observed in the sensitivity to arbekacin during 5 years period. In contrast, a tendency toward decreased sensitivity was observed with vancomycin and teicoplanin, with the tendency more marked with the latter agent. 2. Arbekacin, vancomycin and teicoplanin inhibited the growth of all clinical isolates in the year 2002 at 3.13, 1.56 and 12.5 microg/mL, respectively. 3. The sensitivity to netilmicin tended to decrease over the years. 4. Minocycline, imipenem and ofloxacin had little or no antibacterial activity, with MIC50 of more than 12.5 microg/mL throughout the years studied. 5. Ninety five percent of MRSA strains isolated during the five years were classified as coagulase type II, and enterotoxins were found to be type C in 51% and type AC in 17% of the strains studied.

Aminoglycosides↗
PubMed1979

Cross-sensitivity within the neomycin group of antibiotics.

Neomycin sensitive patients were tested for hypersensitivity to kanamycin, gentamycin, tobramycin, spectinomycin and to the new, not yet registered sisomycin and netilmicin. Cross-sensitivity occured in a considerable part of the patients, except for spectinomycin, the structure of which is basically different from that of the other aminoglycosides tested. The common occurence of cross-sensitivity between neomycin and other aminoglycoside antibiotics shows that it is possible to predict cross-sensitivity between a new drug and an old sensitizing one before clinical reactions from the new drug have occured. Such an investigation should be performed before adopting new antibiotics.

Aminoglycosides↗
PubMed2001

[Short-term versus long-term antimicrobial prophylaxis in abdominal surgery: a multicenter open randomized comparative trial].

OBJECTIVE: To evaluate the outcome of short-term antimicrobial prophylaxis versus long-term in surgical site infection (SSI). METHODS: 731 patients undergoing abdominal operation from 15 hospitals were randomly divided into 2 groups. 358 patients were enrolled in the short-term group (24 h), and 373 patients in the long-term group (72 h). There was no difference between the 2 groups with regard to age, sex, and types operation. Netilmicin was used alone or in combination with metronidazole. RESULTS: The rates of SSI in the short-term and long-term groups were 0.84% and 2.68% (P > 0.05), respectively. CONCLUSIONS: The results demonstrated that the short-term antimicrobial agents prophylaxis is effective in the prevention of post-operative SSI. The long-term one act does not better than the short-term in terms of rationality and pharmacoeconomics.

Abdomen↗
PubMed1991

Pseudomonas aeruginosa resistant to aminoglycosides: an assessment of the currently used methods of disk diffusion and dilution susceptibility.

In recent years, a number of clinical microbiology laboratories have isolated Pseudomonas aeruginosa with the unusual aminoglycoside disk diffusion result of resistance to both amikacin and gentamicin but susceptibility to tobramycin (ArGrTs). A total of 27 isolates of P. aeruginosa reported to have this resistance pattern was retested by the standard National Committee for Clinical Laboratory Standards disk diffusion procedure; twenty strains (74%) were confirmed to be ArGrTs. These twenty isolates were further examined for susceptibility to those aminoglycosides by agar dilution and both micro- and macrodilution methods. Only 25, 25 and 24% of the isolates appeared to be ArGrTs by agar, broth microdilution, and broth macrodilution testing respectively. Most of the remaining isolates were resistant to all three aminoglycosides when tested by broth dilution and resistant only to gentamicin when tested by agar dilution. The percentages of strains resistant to any particular aminoglycoside by agar dilution, broth microdilution and broth macrodilution, respectively were 44, 79 and 69 for amikacin, 95, 91 and 100 for gentamicin, 100, 100 and 100 for netilmicin, 28, 85 and 91 for sisomicin, and 11, 54 and 46 for tobramycin. These results indicate that strains showing the unusual aminoglycoside antibiogram are less susceptible to aminoglycosides in general and should probably be considered borderline resistant to all aminoglycosides. The efficacy of aminoglycosides in the treatment of infections produced by these strains is unknown.

Amikacin↗
PubMed1990

A predictive parameter of antibacterial efficacy in vivo, based on efficacy in vitro and pharmacokinetics.

A method is described to predict the efficacy of antibiotics at changing concentrations in vitro or in an experimental thigh infection in granulocytopenic mice from the activity at constant concentrations in vitro, using pharmacokinetic parameters. The combinations studied were erythromycin against Staphylococcus aureus (in vitro and in vivo), four cephalosporins against two Gram-negative rods (in vivo), netilmicin against Pseudomonas aeruginosa (in vitro) and vancomycin against S. aureus (in vivo). The effect in vitro (ER) was defined as the difference between the growth rate without antibiotic and the growth rate in the presence of an antibiotic. The relationship between concentration and ER was described with the Hill equation. Using pharmacokinetic parameters of exponentially declining concentrations in vitro or of a bi-exponential concentration course in vivo together with the parameters of the Hill equation, the corresponding time course of ER was calculated. By integration with respect to time, an estimate, called ERt, was obtained of the effect on bacterial numbers, called EN, defined as the difference between the number of bacteria in the controls and the number in the presence of the antibiotics. For all antibiotics studied the value of ERt was significantly correlated with the actual values of EN.

Animals↗
PubMed1990

Interactions of antimicrobial combinations in vitro: the relativity of synergism.

Interactions of combinations of netilmicin, amikacin, piperacillin, imipenem, azlocillin, ceftazidime or moxalactam were studied in vitro against Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus. Microtiter checkerboard technique was compared with standard killing curve method and with killing curves obtained in kinetic in vitro models mimicking single or multiple dosing regimens according to human pharmacokinetics. Antibiotic combinations were classified as antagonistic, indifferent or synergistic. Disagreement between classification by checkerboard and by kinetic model was found in 14 of 33 combinations studied (42%). Further analysis by standard killing curve method demonstrated that synergism or antagonism is a relative, not an absolute feature of drug combinations against given pathogens. Factors contributing to disagreements included the concentrations studied relative to the bacterial sensitivity, the ratio of concentrations of the two drugs tested, the size of the bacterial inoculum and the endpoint of the interaction assessment. Standard in vitro methods do not consider changes of antibiotic concentrations over time during combination therapy. Concentrations studied are defined according to bacterial sensitivity (fractions of MIC). Therefore, they may or may not relate to those at the infected site. The observed discrepancies between standard methods for testing drug interaction and a model which more closely reflects human pharmacokinetics support the argument that standard synergy testing provides incomplete data to reliably design clinical combination therapy.

Amikacin↗
PubMed1989

[Toxic shock. Presentation of an obstetrical case].

The case of a 22 years old patient, primigravida, who underwent cesarean for acute fetal distress, and who presented with, at the second day of puerperium, puerperal infection, with clinical picture of shock at the third day, is presented. The clinical picture was preceded by skin rash which became a pyoderma, and ended up as desquamation; there were several alterations: hepatic, renal, hematological (disseminated intravascular coagulation) and digestive (gastroenteritis); and Staphylococcus aureus (coagulase positive) was isolated from the skin, lochia, coproculture; and they were negative to this microorganism the ones from blood, urine and pharynx. The patient received general care for her shock, steroids, blood and fresh plasma and antimicrobial agents (dicloxacillin, cefoperazone and netilmicin). Evolution was favourable, and was discharged at the eleventh day of puerperium in good conditions. A brief summary of the bibliography about this condition, and its very low incidence in our country, is pointed out, as this report is the second one in Latin American literature.

Adult↗