netilmicin and Endocarditis--Bacterial

Topics: Endocarditis, Bacterial; Humans; Netilmicin

This article presents an overview of the aminoglycoside antibiotics used in clinical practice. Facts concerning the discovery and properties of the aminoglycosides are followed by information about spectrums of activity and mechanisms of action and resistance. Individual compounds are compared and proposals on the possibilities for their clinical use, both as single drugs and in combination with beta-lactam antibiotics, are made. The importance placed on measuring the serum concentrations of aminoglycoside antibiotics should serve as a remainder that this procedure is important, on one hand, to increase clinical efficacy and, on the other, to reduce the side effects of these antibiotics. Finally, the aminoglycosides are compared briefly with other antibacterial compounds, some of which are very new. There is no doubt that in the future the aminoglycosides will continue to occupy an important place in the treatment of severe infections, although newly developed agents appear to be effective complements.

Topics: Amikacin; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Microbial; Drug Therapy, Combination; Endocarditis, Bacterial; Gentamicins; Humans; Kanamycin; Kinetics; Neomycin; Netilmicin; Pneumonia; Sepsis; Sisomicin; Streptomycin; Tobramycin

To analyze clinical, bactericidal effectiveness and pharmacokinetics of wide-spectrum antibiotic netromycin (NM).. The trial entered 29 patients: 21 with bronchopulmonary diseases (pneumonia and chronic bronchitis), 5 with exacerbation of chronic pyelonephritis, 2 with infectious endocarditis and 1 with peritonsillar abscess.. Microbiologically, most of the agents (80.36%) showed sensitivity to NM. Pharmacologically, NM persisted long in blood serum and sputum irrespective of the administration mode. Positive clinical dynamics after NM treatment was achieved in all the patients but one who had a peritonsillar abscess.. NM is highly active against both gram-positive and gram-negative flora. Side effects are minimal.

Topics: Adult; Aged; Bacteria; Bronchitis; Endocarditis, Bacterial; Female; Gentamicins; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Netilmicin; Peritonsillar Abscess; Pneumonia; Pyelonephritis

A 2-week course of ceftriaxone (2 g) plus netilmicin (4 mg/kg), administered as one short daily iv infusion, was evaluated for the treatment of streptococcal endocarditis in an open multicenter study. Of the 52 patients, 31 were infected with viridans streptococci, 18 with Streptococcus bovis, two with Gemella morbillorum, and one with group C Streptococcus; 48 patients were assessable. Infection was cured in 42 cases, 35 treated medically and seven treated both medically and surgically. Five patients died without evidence of active infection, and one relapsed. The bacteriologic failure was due to a strain of G. morbillorum against which no synergy of ceftriaxone and netilmicin was evident in vitro. The serum creatinine level increased during treatment in four cases, all involving patients > 65 years old who had renal risk factors; in two of these cases, values did not return to baseline during follow-up. Of 40 patients assessed for auditory function, only one developed decreased perception of borderline significance. Other adverse reactions were mild. This regimen was efficacious, safe, and cost-effective for the treatment of streptococcal endocarditis. However, it must be used with caution for patients with preexisting renal impairment or concomitant exposure to other potentially nephrotoxic agents.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ceftriaxone; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Follow-Up Studies; Humans; Male; Middle Aged; Netilmicin; Prospective Studies; Streptococcal Infections; Treatment Outcome

The dosing frequency of aminoglycoside antibiotics may alter efficacy and toxicity independent of total daily dose. Once-daily tobramycin dosing was compared with continuous infusion in three models of efficacy. Acute pneumonia due to Pseudomonas aeruginosa in guinea pigs responded better to once-daily dosing, and chronic pneumonia in rats and endocarditis in rabbits responded equally to both regimens. Dogs given gentamicin, tobramycin, or netilmicin once daily, with maximum serum concentrations of greater than 100 mg/liter, had less nephrotoxicity than dogs given continuous infusions. Tobramycin was given once daily or continuously to 52 patients with cystic fibrosis who in 10 days had no change in creatinine clearance or hearing despite maximum serum tobramycin concentrations of 40 mg/liter. Intermittent dosing of aminoglycosides, causing infrequent large maximum serum concentrations, may be less toxic and equally efficacious as frequent dosing.

Topics: Adult; Animals; Anti-Bacterial Agents; Cystic Fibrosis; Dogs; Dose-Response Relationship, Drug; Drug Administration Schedule; Endocarditis, Bacterial; Female; Gentamicins; Glomerular Filtration Rate; Guinea Pigs; Humans; Male; Netilmicin; Pneumonia; Pseudomonas Infections; Rabbits; Rats; Rats, Inbred Strains; Tobramycin

Aminoglycosides are recommended for the treatment of Enterococcus faecalis infections, especially in severe and bacteremic infection. However, the optimal aminoglycoside or the optimal dosage remains uncertain. This study aimed to compare the activity of four aminoglycosides against E. faecalis (gentamicin, netilmicin, tobramycin, and amikacin) and two dosages of gentamicin. One clinical strain of E. faecalis was used to induce aortic endocarditis in the study rabbits. Each aminoglycoside was infused daily over 3 days with a computer-regulated flow simulating human pharmacokinetics of 15 mg/kg/day for amikacin, 6 mg/kg/day for netilmicin, and 3 mg/kg/day for gentamicin and tobramycin. Additionally, two dosages of gentamicin (simulating 3 or 6 mg/kg/day) were compared over 1 or 3 days of treatment. The in vivo efficacy was assessed according to the bacterial count in vegetations, in comparison with a control group. Of the four aminoglycosides tested, only gentamicin and netilmicin showed significant antibacterial efficacy after 3 days of treatment. After only 1 day of treatment, the high dosage of gentamicin (6 mg/kg/day) was more effective than the standard dosage (3 mg/kg/day). Among the tested aminoglycosides, gentamicin showed the best efficacy, with the best results after 24 h of treatment for the highest dosage.

Topics: Amikacin; Animals; Anti-Bacterial Agents; Bacterial Load; Disease Models, Animal; Drug Administration Schedule; Drug Evaluation, Preclinical; Endocarditis, Bacterial; Enterococcus faecalis; Female; Gentamicins; Gram-Positive Bacterial Infections; Netilmicin; Rabbits; Time Factors; Tobramycin

Enterococcal endocarditis can be very difficult to eradicate, requiring prolonged treatment with a combination of a penicillin and an aminoglycoside. In this patient with a pacemaker associated enterococcal endocarditis, ototoxicity occurred due to total gentamicin dose despite plasma concentrations consistently within the treatment range. Substitution with netilmicin, without a break in aminoglycoside treatment, resulted in a rapid improvement in hearing and allowed the required course of aminoglycoside to be completed. The risk factors for ototoxicity with gentamicin are reviewed, in particular the dangers of increasing age and of multiple and prolonged courses. Close treatment monitoring does not totally avoid this risk, especially when prolonged aminoglycoside treatment is required. This case emphasises the need for prompt investigation and adequate, definitive treatment of enterococcal endocarditis to avoid the increased risk consequent on repeated courses of antibiotics. The resolution of the ototoxicity with netilmicin is consistent with other reports of lower cochleotoxicity than with other aminoglycosides.

Topics: Aged; Anti-Bacterial Agents; Endocarditis, Bacterial; Equipment Contamination; Gentamicins; Gram-Positive Bacterial Infections; Hearing Loss, Sensorineural; Humans; Male; Netilmicin; Pacemaker, Artificial

Yersinia enterocolitica is a gram-negative coccobacillus. Y. enterocolitica infection is acquired by humans via the oral route. Infection due to Y. enterocolitica was first observed in 1933 in New York. Y. enterocolitica septicemia has been increasingly recognized in recent years, whereas endocarditis due to Y. enterocolitica is a rare manifestation. We herein describe a patient who developed Y. enterocolitica endocarditis and was successfully treated with a combination of drugs consisting of a quinolone (ofloxacin) and an aminoglycoside (netilmicin).

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Drug Therapy, Combination; Endocarditis, Bacterial; Humans; Male; Middle Aged; Netilmicin; Ofloxacin; Treatment Outcome; Yersinia enterocolitica; Yersinia Infections

This article describes three extremely low birth weight infants with Staphylococcus aureus septicemia associated with insertion of a percutaneous central venous catheter who later developed endocarditis. Echocardiography demonstrated large vegetations although only one infant had a murmur. Following a 6-week course of intravenous flucloxacillin and netilmicin, the endocarditis completely resolved and further intervention was unnecessary, although one baby died later as a result of volvulus and chronic lung disease. Echocardiography should be performed to exclude invasive infection in infants with S. aureus septicemia even when there is no murmur or other evidence of endocarditis. If endocarditis is identified, a good outcome is possible with appropriate aggressive antibiotic therapy.

Topics: Anti-Bacterial Agents; Diagnosis, Differential; Endocarditis, Bacterial; Female; Floxacillin; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Male; Netilmicin; Staphylococcal Infections; Staphylococcus aureus; Ultrasonography

Topics: Adult; Amoxicillin; Diagnosis, Differential; Endocarditis, Bacterial; Gentamicins; Humans; Male; Netilmicin; Osteoarthropathy, Secondary Hypertrophic; Penicillins; Streptococcal Infections; Streptococcus sanguis; Time Factors

Two children with cyanotic congenital heart disease and Gram negative bacterial infection of prosthetic material after cardiac surgery were treated successfully with oral ciprofloxacin, initially in combination with netilmicin. The use of oral ciprofloxacin allowed prolonged outpatient treatment to be given, avoiding the need for intravenous access and early repeat surgery.

Topics: Anti-Infective Agents; Blood Vessel Prosthesis; Child; Child, Preschool; Ciprofloxacin; Drug Therapy, Combination; Endocarditis, Bacterial; Gentamicins; Humans; Male; Netilmicin; Prosthesis-Related Infections

Using a rabbit model of aortic valve endocarditis, we studied the efficacy of vancomycin alone or in combination with netilmicin and/or rifampin against a methicillin- and gentamicin-resistant strain of Staphylococcus aureus (MGRSA). Antibiotics were given for 6 to 12 days, as follows: vancomycin (15 mg/kg of body weight every 12 h [BID] intravenously), vancomycin plus netilmicin (2.5 mg/kg BID intramuscularly), vancomycin plus rifampin (10 mg/kg BID intramuscularly), and vancomycin plus netilmicin plus rifampin at the same routes, dosages, and schedules mentioned above. Netilmicin was given to two additional groups at a higher dosage (6 mg/kg every 24 h intramuscularly) alone or in combination with vancomycin (15 mg/kg BID intravenously) for 12 days. All regimens resulted in undetectable bacterial counts in a significant proportion of vegetations (except netilmicin alone) or reduced the bacterial counts in the vegetations compared with the counts in the untreated controls (P<0.01 to P<0.001). No resistance to rifampin or netilmicin developed during therapy. It is concluded that in the treatment of experimental aortic valve endocarditis caused by MGRSA (i) vancomycin as monotherapy is as efficacious as the triple combination, (ii) the addition of netilmicin (once daily or BID) to vancomycin does not improve the efficacy of the latter antibiotic, even in the presence of rifampin, and (iii) a 12-day course in more effective than a 6-day one, but not at a statistically significant level.

Topics: Animals; Anti-Bacterial Agents; Drug Therapy, Combination; Endocarditis, Bacterial; Gentamicins; Methicillin Resistance; Microbial Sensitivity Tests; Netilmicin; Rabbits; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

The treatment of endocarditis often requires prolonged antibiotic therapy. Individualized drug dosage regimens have made such therapy possible even in patients with impaired renal function. However, the problem of efficacy remains. Especially for aminoglycosides, it would be a useful guide to have at least an approximate idea of the concentration of an antibiotic within an endocardial vegetation. This study was designed to develop software to model the drug concentrations at different layers within spherical vegetations to provide a guide during clinical therapy of patients with endocarditis. A general model describing the diffusion of antibiotics in spheres has now been developed and interfaced with the USC*PACK PC Clinical Programs in order to compute and plot concentrations, within the vegetation, based on the regimen given to the patient and the diffusitivity of the antibiotic into the vegetation. Some preliminary results of this research, which are still in progress, are presented. Diffusion into simulated spherical vegetations has been computed for different treatment regimens for endocarditis: amikacin or netilmicin and vancomycin were given to three elderly patients (3 women, 74, 75 and 92 years old, with initial estimated creatinine clearances of 51, 36, and 31 ml/min/1.73 m2, respectively). Although Amikacin has a low diffusivity, the concentrations, even in the center of the vegetation, appear to be effective. The effects of various regimens, including a 'once-a-day' aminoglycoside regimen, are presented.

Topics: Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Diffusion; Drug Administration Schedule; Drug Monitoring; Drug Therapy, Computer-Assisted; Endocarditis, Bacterial; Female; Humans; Models, Biological; Models, Chemical; Netilmicin; Software; Vancomycin

We performed experiments in rats aimed at determining whether a combination of ceftriaxone (CRO) and netilmicin (NET), by using once-daily administration in rats, which simulated profiles of drug in human serum, was more effective than either agent alone in the treatment of endocarditis caused by viridans group streptococci. A programmable infusion pump system enabled the production of profiles of CRO in serum that simulate those found in humans after the intravenous administration of 2 g. The subcutaneous administration of 18 mg of NET per kg of body weight produced levels in the sera of rats comparable to those after the intravenous administration of a dose of 5 mg of NET per kg in humans. Rats with catheter-induced aortic vegetations were infected intravenously with two test strains, a CRO-susceptible Streptococcus sanguis strain (MICs of CRO and NET, 0.064 and 8 mg/liter, respectively) and a relatively CRO-resistant Streptococcus mitis strain (MICs of CRO and NET, 2 and 8 mg/liter, respectively). Against both strains, the combination of CRO and NET was synergistic in vitro as determined by time-kill curves. Treatment of rats was started 48 h postinfection and lasted for 3 days. CRO alone was effective against the susceptible strain (P < 0.001 compared with control animals) but was not effective against the resistant organism. A significantly enhanced antibacterial activity of the CRO-NET combination in reducing the valvular bacterial counts was observed with both test strains (P < 0.001). The synergistic effect was obtained with a single daily injection of NET which provided detectable levels in serum for only 8 h, suggesting that in vivo synergism in the treatment of infections caused by viridans group streptococci can be obtained without 24 h of aminoglycoside coverage. These experimental data might provide a rationale for clinical trials of a once-a-day dosing regimen in the treatment of streptococcal but nonenterococcal endocarditis.

Topics: Animals; Ceftriaxone; Endocarditis, Bacterial; Female; Humans; Infusion Pumps; Microbial Sensitivity Tests; Netilmicin; Rats; Rats, Wistar; Serum Bactericidal Test; Streptococcal Infections; Streptococcus; Streptococcus sanguis

Serious complications, such as emboli and mycotic aneurysms, are still frequent in documented cases of infective endocarditis. Infecting organisms other than Streptococcus viridans and Staphylococcus are becoming more common.. A 8 year-old girl was admitted because of a sudden pain in the right calf followed by complete disability. She had low-grade fever and presented with a moderate heart murmur with no sign of congestive heart failure, a severe pain at palpation of her calf with no Homans sign; she had many dental caries. Laboratory data indicated leukocytosis with increased percentage of polymorphonuclear cells and increased sedimentation rate. Ultrasonography of the calf showed laceration of the muscle with blood suffusion. Echocardiography showed vegetations involving the mitral valve. Intravenous antibiotic therapy with penicillin G and netilmicin was instituted, but mitral insufficiency appeared 7 days later while the fever persisted. At that time, the brain CT scan showed ischemic lesions, while angiography showed several mycotic aneurysms. Neisseria mucosa was recovered from the 5 initial blood cultures 16 days after the onset, and penicillin G was replaced by ampicillin. A second vegetation involving the aortic valve was seen a few days later, and a recent arterial embolism to the right leg was suspected because fever and pain reappeared. The brain ischemic lesions gradually disappeared and a second angiography performed 3 months after the first showed that all but one large mycotic aneurysm had disappeared; this last aneurysm was excised. Four years later, the child is in good health without any neurological sequelae but having mitral insufficiency.. This girl presented with classical complication of infective endocarditis due to Neisseria mucosa, a saprophytic organism of the oral cavity. This is the second report of such an infection in children.

Topics: Ampicillin; Aneurysm, Infected; Child; Endocarditis, Bacterial; Female; Humans; Intracranial Aneurysm; Neisseria; Neisseriaceae Infections; Netilmicin; Penicillin G

We have conducted experiments to determine if one daily injection of netilmicin (NET) would be synergistic with the broad-spectrum cephalosporin ceftriaxone (CRO) in the treatment of experimentally induced endocarditis. Rats with catheter-induced aortic vegetations were infected intravenously with 3 x 10(7) CFU of a beta-lactam-sensitive strain of Streptococcus sanguis or a beta-lactam-resistant strain of Streptococcus mitis. Treatment with the antibiotics alone (CRO, 10 mg/kg of body weight every 8 h; NET, 18 mg/kg every 24 h) or in combinations which had proved synergistic in in vitro time-kill curves was commenced 48 h postinfection and continued for 72 h. The results show that the combination was markedly effective against S. sanguis and moderately effective against S. mitis, while, with the protocol used here, the agents alone were not. The results suggest that CRO-NET should be an effective combination for treating streptococcal endocarditis in humans and may permit a shorter duration of treatment and once-a-day dosing to be used.

Topics: Animals; Ceftriaxone; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Microbial Sensitivity Tests; Netilmicin; Rats; Rats, Wistar; Serum Bactericidal Test; Streptococcal Infections; Streptococcus; Streptococcus sanguis

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.

Topics: Adult; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Heart Valve Prosthesis; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Netilmicin; Prosthesis-Related Infections; Staphylococcal Infections; Staphylococcus epidermidis; Vancomycin

A patient with Haemophilus aphrophilus endocarditis was successfully treated with ciprofloxacin. The response to treatment with cefotaxime and netilmicin for 12 days was poor but was satisfactory to a 6 weeks' course of ciprofloxacin.

Topics: Adult; Cefotaxime; Ciprofloxacin; Endocarditis, Bacterial; Haemophilus Infections; Humans; Male; Microbial Sensitivity Tests; Netilmicin

The penicillin-aminoglycoside combination is recommended for the treatment of systemic enterococcal infections. However, the optimal dosing regimen of the aminoglycoside remains to be elucidated. We evaluated the efficacy of penicillin, alone or in combination with various dosing regimens of netilmicin, for the treatment of experimental left-sided Enterococcus faecalis endocarditis in rabbits. Animals were injected intramuscularly for 4 days with penicillin alone or in combination with netilmicin in one of the following regimens: netilmicin at a low dose (2 mg/kg of body weight every 8 h), netilmicin at a high dose (4 mg/kg every 8 h), or netilmicin at a single daily high dose (12 mg/kg every 24 h). MICs and MBCs were 3.1 and 6.2 micrograms/ml and 8 and 8 micrograms/ml for penicillin and netilmicin, respectively. A netilmicin concentration of 4 micrograms/ml was the lowest concentration that achieved synergism with penicillin, as shown by the kill-curve method. Mean peak levels of netilmicin in serum were 5.6 (netilmicin at 2 mg/kg), 9.8 (netilmicin at 4 mg/kg), and 20.6 (netilmicin at 12 mg/kg) micrograms/ml. Mean penicillin levels in serum were constantly above the MIC. Penicillin plus netilmicin at a high dose given three times daily was more effective (P less than 0.05) than any other regimen in reducing bacterial titers in vegetations and was the only treatment that induced a significant bactericidal activity in rabbit serum during the trough. We concluded that divided doses of aminoglycoside are more effective than the same total dose given once daily in combination with penicillin. Our data suggest that prolonged levels of aminoglycoside in serum might be important to exhibit the greatest in vivo efficacy of the combination against E. faecalis. They also indicate that use of a reduced total daily dose of aminoglycoside or an increase in the interval between each dose might reduce the efficacy of therapy in animals with this type of infection.

Topics: Animals; Anti-Bacterial Agents; Biological Assay; Blood Bactericidal Activity; Drug Synergism; Drug Therapy, Combination; Endocarditis, Bacterial; Enterococcus faecalis; Female; Microbial Sensitivity Tests; Netilmicin; Penicillins; Rabbits

We studied the efficacy of sulbactam, a beta-lactamase inhibitor, in combination with ceftriaxone in vitro and in experimental endocarditis due to an Escherichia coli strain producing an extended-spectrum beta-lactamase most similar to SHV-2, a new mechanism of resistance to broad-spectrum cephalosporins among members of the family Enterobacteriaceae. In vitro, ceftriaxone demonstrated an important inoculum effect (MICs were 2 and 256 micrograms/ml with 5 X 10(5) and 5 X 10(7) CFU of inoculum per ml, respectively). Sulbactam inhibited the beta-lactamase degradation of ceftriaxone and enhanced the killing by ceftriaxone with both inocula tested. In vivo, sulbactam (100 mg/kg every 8 h) or ceftriaxone (15 or 30 mg/kg every 24 h) alone were ineffective after a 4-day therapy. The addition of sulbactam to ceftriaxone (15 mg/kg) or to the ceftriaxone (15 mg/kg)-netilmicin (6 mg/kg every 24 h) combination produced a reduction of 2 log10 CFU/g of vegetation greater than that produced by therapy without sulbactam. The sulbactam-ceftriaxone (30 mg/kg) combination produced a reduction of almost 5 log10 CFU/g of vegetation greater than that produced by single-drug therapy (P less than 0.01), sterilized five of eight vegetations (versus none of seven for ceftriaxone [30 mg/kg] alone; P less than 0.05), and was as effective as the ceftriaxone (15 mg/kg)-sulbactam-netilmicin combination. We concluded that (i) SHV-2 production was responsible for ceftriaxone failure in vivo, probably because of the high inoculum present in vegetations; (ii) sulbactam used in a regimen which provided levels in serum constantly above 4 micrograms/ml and a vegetation/serum peak ratio of approximately 1:3 enhanced the activity of a broad-spectrum cephalosporin in a severe experimental infection; and (iii) the highest dose of ceftriaxone in combination with sulbactam was as effective as the lowest dose of ceftriaxone plus sulbactam plus an aminoglycoside.

Topics: Animals; beta-Lactamase Inhibitors; Ceftriaxone; Drug Combinations; Endocarditis, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Microbial Sensitivity Tests; Netilmicin; Rabbits; Sulbactam

The activity of penicillin alone and combined with aminoglycoside on endocarditis strains of streptococci was examined. Good assay reproducibility was obtained by the use of logarithmic phase cultures standardised by opacity, careful inoculation of well-plates, removal of antibiotic by membrane transfer and incubating survival counts in hydrogen plus carbon dioxide. The use of 10-fold intervals for penicillin concentration simplified assay design without loss of efficiency.

Topics: Drug Therapy, Combination; Endocarditis, Bacterial; Gentamicins; Humans; Microbial Sensitivity Tests; Netilmicin; Penicillin G; Streptococcus

Thrombotic obstruction is rare in bacterial endocarditis involving prosthetic heart valves. A 45-year-old man who had three intracardiac, ball-cage-type prosthetic valves, presented with streptococcal septicemia. Major obstruction of the tricuspid Smeloff-Cutter valve and normal function of the two other prostheses were documented by Doppler echocardiography. Emergency replacement of the tricuspid valve alone was decided on the one basis of this echocardiographic diagnosis, and successfully performed. Operative findings confirmed the noninvasive findings.

Topics: Ampicillin; Aortic Valve; Bioprosthesis; Combined Modality Therapy; Echocardiography, Doppler; Endocarditis, Bacterial; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Netilmicin; Postoperative Complications; Prosthesis Design; Prosthesis Failure; Rheumatic Heart Disease; Streptococcal Infections; Tricuspid Valve

We evaluated the activities of ceftriaxone (15 mg/kg), netilmicin (6 mg/kg), and their combination given intramuscularly once daily for 4 days for the treatment of experimental Escherichia coli endocarditis in rabbits. In vitro, a greater rate of killing and an increased trough serum bactericidal titer (P less than 0.01) were achieved with the combination. In vivo, the combination had a greater bactericidal effect (P less than 0.01) and resulted in a greater number of sterile vegetations (P less than 0.05) than single-drug therapy. Thus, in vivo, an increased effect can be obtained despite a single daily dose of a long-acting cephalosporin and an aminoglycoside.

Topics: Animals; Ceftriaxone; Drug Combinations; Endocarditis, Bacterial; Escherichia coli Infections; Female; Half-Life; Humans; Male; Netilmicin; Rabbits

Seven strains of viridans streptococci isolated from patients with endocarditis were inhibited in vitro by 0.06-2 mg/l and 0.016-0.5 mg/l of the penems FCE 22101 and FCE 24362 respectively. The MBCs were the same or two-fold higher than the respective MIC with three exceptions. One strain of Streptococcus faecalis was only inhibited (8 mg/ml respectively 0.5 mg/l; MBC greater than 32 mg/l) and one strain of Str. faecium was resistant (MIC greater than or equal to 16 mg/l). When combined with gentamicin or netilmicin a bactericidal and synergistic killing was observed within 1-8 h in all strains except Str. faecium. Synergy could also be confirmed in all cases by following bacterial growth kinetics after elimination of antibiotics, by calculating the difference between the times required for bacteria exposed to antibiotic and unexposed bacteria to increase in numbers (PAE).

Topics: Anti-Bacterial Agents; Carbapenems; Drug Synergism; Endocarditis, Bacterial; Gentamicins; Humans; Lactams; Microbial Sensitivity Tests; Netilmicin; Streptococcus; Time Factors

Among 31 strains of coagulase-negative staphylococcus (CNS) causing endocarditis in individual patients, 16 had MIC of teicoplanin greater than or equal to 8 mg/l (MIC50, 8; MIC90, 8; MIC range, 0.5-32 mg/l); and 24 had MBC greater than or equal to 16 mg/l (MBC50, 32; MBC90, 64; MBC range, 4-128 mg/l). Greater sensitivity was shown to vancomycin (MIC50, 2; MIC90, 4; MIC range, 1-8 mg/l; MBC50, 2; MBC90, 4; MBC range, 0.5-8 mg/l). Teicoplanin-resistant CNS (MIC, greater than or equal to 8 mg/l) were detected in the anterior nares of two of three patients and six of nine staff, and in the air, of a cardiac surgery unit, and in other series of CNS of clinical origin. The results of in-vitro sensitivity testing of CNS to teicoplanin are dependent on the media and conditions used, and their clinical significance has not been determined. Nevertheless, the findings reported here put in question the use of teicoplanin alone as prophylaxis during valve replacement surgery.

Topics: Cardiac Surgical Procedures; Coagulase; Coronary Care Units; Drug Resistance, Microbial; Endocarditis, Bacterial; Glycopeptides; Humans; In Vitro Techniques; Netilmicin; Personnel, Hospital; Staphylococcal Infections; Staphylococcus; Staphylococcus epidermidis; Teicoplanin; Vancomycin

Topics: Adult; Aortic Valve; Drug Therapy, Combination; Endocarditis, Bacterial; Humans; Male; Netilmicin; Penicillins; Streptococcus

Haemophilus segnis is a rarely recognised commensal in the oropharynx. We wish to report the first published case of endocarditis caused by H. segnis. The patient, a 76-year-old female did not recover until after 2 courses of ampicillin given for a total of 57 days. In the second course of treatment, ampicillin was combined with 10 days of netilmicin therapy.

Topics: Aged; Ampicillin; Antibodies, Bacterial; Echocardiography; Endocarditis, Bacterial; Female; Haemophilus; Haemophilus Infections; Humans; Immunoelectrophoresis, Two-Dimensional; Netilmicin

A 59-year-old man developed septicaemia caused by Kingella denitrificans. Treatment was with ampicillin and an aminoglycoside. The illness was complicated by a cerebral embolus. An obvious source of infection was not found.

Topics: Ampicillin; Endocarditis, Bacterial; Gram-Negative Aerobic Bacteria; Humans; Male; Middle Aged; Neisseriaceae; Netilmicin; Sepsis

Left-sided endocarditis caused by Pseudomonas aeruginosa is frequently associated with failure of medical therapy in man. The efficacy of ciprofloxacin and netilmicin + azlocillin has been studied in 79 rabbits with aortic valve endocarditis caused by a serum-resistant strain of P. aeruginosa. Infected animals received either: no therapy; ciprofloxacin (80 mg/kg/day); or netilmicin (6.5 mg/kg/day) + azlocillin (400 mg/kg/day). Ciprofloxacin significantly lowered vegetation titers of P. aeruginosa at days 6 and 10 of therapy compared with netilmicin + azlocillin (P less than 0.001). Similarly, ciprofloxacin was significantly more effective in sterilizing vegetations (P less than 0.005), curing P. aeruginosa endocarditis (P less than 0.001), and preventing bacteriological relapse after discontinuing antibiotic therapy (P less than 0.005). Both antibiotic regimens were equally effective in sterilizing renal abscesses. Resistance to azlocillin was occasionally observed in vivo among P. aeruginosa isolates within cardiac vegetations during the second week of therapy, but not to ciprofloxacin or netilmicin.

Topics: Abscess; Animals; Anti-Infective Agents; Aortic Valve; Azlocillin; Ciprofloxacin; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Kidney Diseases; Microbial Sensitivity Tests; Netilmicin; Penicillin Resistance; Pseudomonas Infections; Quinolines; Rabbits

Topics: Aged; Cephalothin; Child; Drug Antagonism; Endocarditis, Bacterial; Floxacillin; Fusidic Acid; Gentamicins; Humans; Male; Netilmicin; Staphylococcal Infections; Streptococcal Infections

Pericardial fluid, serum and atrial appendage concentrations of netilmicin and gentamicin were determined in 80 patients who received one or two pre-operative doses of either netilmicin 200 mg im or gentamicin 120 mg im. Mean atrial appendage concentrations of netilmicin and gentamicin after a single dose were 4.8 and 2.1 mg/kg; mean serum concentrations were 6.9 and 3.9 mg/l, and mean pericardial fluid concentrations 3.8 and 2.6 mg/l, respectively. After two doses apparent sequestration of the antibiotic in pericardial fluid was observed. A review of the cases of prosthetic valve endocarditis during the last decade suggests that aminoglycoside/isoxazolyl penicillin combinations provide good anti-staphylococcal prophylaxis. A change in the pattern of infections has been observed. The incidence of staphylococcal infection has fallen; early infections may be of fungal aetiology and late infections show a similar distribution of infecting organisms to that seen in native valve endocarditis.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Cardiac Surgical Procedures; Endocarditis, Bacterial; Gentamicins; Heart Valve Prosthesis; Humans; Netilmicin; Premedication

The combination of penicillin plus netilmicin was synergistic in vitro against 28 strains of Streptococcus faecalis and compared favorably with penicillin in combination with gentamicin. Similarly, penicillin plus netilmicin was as effective as penicillin plus gentamicin in the therapy of 67 rabbits with enterococcal endocarditis produced with a streptomycin-susceptible (S) or a streptomycin-resistant (R) strain of S. faecalis. After 5 days of infection, control rabbits had bacterial titers of 10(10) colony-forming units (CFU)/g of vegetation. Those treated with penicillin plus netilmicin had mean titers of 10(5.2) and 10(5.1) CFU/g for S and R strains, respectively, and those treated with penicillin plus gentamicin had mean valve titers of 10(5.8) CFU/g for both strains. After 10 days of therapy, mean valve titers with penicillin plus netilmicin were 10(3.8) and 10(4.7) CFU/g, and with penicillin plus gentamicin they were 10(4.5) and 10(5.4) CFU/g for S and R strains, respectively. Thus, if netilmicin proves to be less toxic than other aminoglycoside antibiotics, it may have potential usefulness in the therapy of enterococcal endocarditis.

Topics: Animals; Drug Synergism; Endocarditis, Bacterial; Enterococcus faecalis; Gentamicins; Humans; Microbial Sensitivity Tests; Netilmicin; Penicillins; Rabbits; Streptococcal Infections

Successful therapy of enterococcal endocarditis requires the use of a combination of penicillin plus an aminoglycoside. The effectiveness of penicillin (Pen), streptomycin (Str), and netilmicin (Net), a new aminoglycoside, alone and in combination, were studied in vitro and in the treatment of left-sided enterococcal endocarditis in rabbits. In vitro Pen+Str or Net resulted in a more rapid and more complete bactericidal effect than Pen, Str, or Net alone against a Str-susceptible strain of enterococcus (strain 1). Against a highly Str-resistant strain (strain 2), Pen+Net showed an advantage over Pen, Str, or Net alone, or Pen+Str. Endocarditis was produced in rabbits with strain 1 or 2, and treatment was initiated 24 h later. Rabbits were treated for 48 h or 5 days with procaine Pen, Pen+Str, or Pen+Net. With strain 1, numbers of enterococci in the vegetations decreased more rapidly with Pen+Str or Pen+Net treatment than with Pen, Str, or Net alone. With strain 2, Pen+Net showed a clear advantage over Pen, Str, Net, or Pen+Str. Net in combination with Pen showed synergistic in vitro activity and was more effective than Pen alone in the treatment of enterococcal endocarditis in rabbits caused by both Str-susceptible and Str-resistant strains.

Topics: Animals; Drug Therapy, Combination; Endocarditis, Bacterial; Enterobacteriaceae Infections; Enterococcus faecalis; Female; Netilmicin; Penicillin Resistance; Penicillins; Rabbits; Streptococcal Infections; Streptomycin