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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.
Fifty patients with acute non-lymphocytic leukaemia were treated by random allocation with either ceftazidime alone or a combination of piperacillin, netilmicin and cefotaxime for 65 febrile neutropenic episodes. Nineteen of 33 patient episodes (58%) responded to ceftazidime alone compared with 21 of 32 episodes (66%) treated with the combination. There was one infective death in a patient given the combination; rates of documented superinfection were low. The treatment groups appeared identical in terms of patient demography, underlying disease and other risk factors, though patients with a clinical site of infection responded more slowly than those without. Bacteraemia per se did not appear to influence outcome. Bactericidal serum concentrations greater than or equal to 8 X the minimum bactericidal concentration were predictive of a rapid response (within 4 days) to antibiotics. Furthermore, serum from patients treated with ceftazidime maintained adequate cidal activity against Pseudomonas aeruginosa for longer than that obtained from patients treated with the three-drug combination. Ceftazidime was shown to be a safe and effective alternative to the three-drug combination for the initial management of febrile neutropenic episodes in leukaemic patients.
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.
Hemodiafiltration (HDF) is a new dialysis treatment that combines convective and diffusive forces. In order to assess the efficiency of a peculiar model of hypertonic HDF (H HDF), we studied eight uremic patients when they were undergoing five sessions of H HDF of 180 minutes duration and two sessions of standard hemodialysis (HD) of 270 minutes duration with a comparable blood (approximately 400 mL/min) and dialysate flow rate (approximately 520 mL/min). The plasma water clearances (Kw) of small [urea (U), creatinine (C), uric acid (UA), and phosphorus (P)] and middle molecules [netilmicin (N) and inulin (I)] were exceedingly higher in H HDF than in HD; however, because of the different treatment times, U and C removal (R) in HD overcame and UA and P R in HD equalized that in H HDF. The factor time was not sufficient to HD to compensate for the large difference in Kw in the case of I. Additional studies were performed in seven out of the eight patients after two sessions of H HDF and one session of HD. Two significantly higher rebounds were observed when comparing both treatments: for U after HD and for parathyroid hormone (PTH) after H HDF; however, PTH Cx/Cs ratios (ratios of the plasma water concentration of PTH at any postdialysis time to the plasma water concentration of PTH at the start of the run) were not different in both treatments, meaning that there was an increased PTH secretion in the early post H HDF hours in order to compensate for the larger PTH R with H HDF.(ABSTRACT TRUNCATED AT 250 WORDS)
Following the development of a sensitive high-performance liquid chromatographic (HPLC) assay for gentamicin in biological matrices, the utility of this assay for the determination of other clinically important aminoglycosides (neomycin, netilmicin and sisomicin) in bacterial culture media or plasma is demonstrated. The high sensitivity of the assay enables direct measurement of the aminoglycoside content of bacterial cells cultured in the presence of unlabelled drug.
Enterococci with gentamicin MICs of 256 to 1,024 micrograms/mL were evaluated for susceptibility to ampicillin plus gentamicin synergism. Sixteen of eighteen enterococcal isolates were not susceptible to synergistic killing by ampicillin plus gentamicin; 11 possessed aac(6')-aph(2"), and 4 possessed aph(2")-Ic. A gentamicin MIC of 512 or 1,024 micrograms/mL predicted lack of ampicillin/gentamicin synergism, but a gentamicin MIC of 256 micrograms/mL did not. For six enterococcal strains possessing the gentamicin-resistance gene aph(2")-Ic, ampicillin plus dibekacin, ampicillin plus netilmicin, and ampicillin plus amikacin produced synergistic killing in five, three, and two strains, respectively.
Some antibiotics at sub-inhibitory concentrations are able to alter bacterial surface structures and modulate adhesiveness by affecting the expression of microbial adhesins. An important mechanism of pulmonary defence against pathogens is SP-A, one of the proteins of the alveolar surfactant having opsonizing activity. The aim of this study was to investigate the effect that sub-inhibitory concentrations of different antibiotics and physiological concentrations of SP-A (1 and 5 microg/ml) could exert on the adherence of respiratory pathogens to the bronchial epithelial cell line, WI26VA4. Cefdinir and clarithromycin showed high efficacy, mainly at 1/2 MIC, in reducing the adherence of Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae strains to values lower or equal to 50% of the control; sparfloxacin showed the same effect on S. aureus and S. pneumoniae but teicoplanin only on S. pneumoniae. Other similar results were observed with netilmicin on Klebsiella pneumoniae (40%) and with cefepime and ciprofloxacin on Pseudomonas aeruginosa (60%). Clarithromycin reduced the adherence of K. pneumoniae to 80% although it is not active against this strain. Adherence of the test strains was not modified by SP-A alone or in combination with any of the antibiotics used.
BACKGROUND: Materno-fetal infection due to Pasteurella multocida is rare; it may be severe in the neonate. CASE REPORT: A 27-year old woman was admitted at 37 weeks' gestation with a history of abdominal cramps. Twenty-four hours after delivery, the mother was febrile (40 degrees C) and was given intravenous cefotaxime (2 days), followed by cefpodoxime (15 days). The newborn was febrile and hypotonic 24 hours after birth; he received an infusion of hydroxyethylamidon and was given cefotaxime (3 days), netilmicin (6 days) and amoxicillin (10 days). Pasteurella multocida was isolated from placenta, blood and gastric fluid in the baby and in blood cultures and vaginal swab in the mother. It was established that the mother was bitten by her dog during the pregnancy and wounded a few days before delivery. CONCLUSION: This neonate was infected during the delivery and the source of mother's contamination was easy to determinate: pet animals were kept by the family and there was an history of wounds during her pregnancy.
The interactions of a number of aminoglycoside antibiotics with tRNA and DNA were studied by an HPLC method. based on tRNA and DNA peak size exclusion. Among the compounds studied (deoxystreptamine, neamine, neomycin B, kanamycin A, gentamicin A, netilmicin, streptomycin, and the synthetic neamine analogue BKN3), neomycin B and the synthetic analogue of neamine were proved to be the most potent binders.
BACKGROUND: A study was designed to assess a computer-based program for continuous registration of antibiotic resistance, statistics concerning severity of illness, and consumption of antibacterial drugs. METHODS: The frequency of antibiotic resistance among bacteria in eight ICUs in southeastern Sweden was investigated yearly from 1995 through 1997. The antibiotic consumption in the ICUs was registered as defined daily doses (DDD) and compared to severity of illness (APACHE-II scores). RESULTS: There was a statistically significant increase in ampicillin resistance among Enterococcus spp. between 1996 and 1997, which was due to a shift from Enterococcus faecalis to Enterococcus faecium. A high prevalence of resistance among coagulase-negative staphylococci to oxacillin (approximately 70%), ciprofloxacin (approximately 50%), fucidic acid (approximately 50%) and netilmicin (approximately 30%) was seen in all ICUs during the whole study period. There was a statistically significant increase in ciprofloxacin resistance among Escherichia coli and Enterococcus spp. The resistance among Enterobacter spp. to cefotaxime decreased but this change was not statistically significant. Efforts were made to avoid betalactam antibiotics, except carbapenems, for treatment of infections caused by Enterobacter spp. and the consumption of cephalosporins decreased whereas the consumption of carbapenems increased. The total antibiotic consumption decreased by 2.5% during the study period. There was no correlation between APACHE II scores and antibiotic consumption. CONCLUSIONS: Each ICU within a hospital ought to have a program for "on-line" antibiotic resistance surveillance of drugs used in that unit so that changes in empirical treatment can be made when there is an increase in antibiotic-resistant isolates within that unit.
Different methods have been described for determination of the post-antibiotic effects (PAEs) of antibiotics, from the conventional methods to the automatic measurement of bacterial regrowth. The PAEs of ciprofloxacin, ofloxacin and perfloxacin, as compared with those of amikacin, netilmicin and ceftazidime, have now been investigated for three clinical isolates of Pseudomonas species, using automated measurement of the growth with an Anthos microplate reader. It was found that, besides the well-known PAEs of aminoglycosides, quinolone antibiotics also exhibit drug- and concentration-dependent PAEs against clinical isolates of Pseudomonas when used in concentrations of 1/2x, 1 x or 5 x MIC. Of the three quinolones tested, pefloxacin showed the greatest PAE, independently of its MICs against the different strains. Ofloxacin had no or only an insignificant PAE, while ciprofloxacin had a marked PAE for all strains, including the reference strains.
Pregnant Wistar females were treated with gentamicin (G), netilmicin (N) or amikacin (A) during two periods of pregnancy covering organogenesis and the beginning of nephrogenesis. Deliveries occurred normally. We studied functional effects--influence of sex, litter size, diuresis, creatinine clearance, G-kidney concentration, and kidney morphological alterations--in rat neonates on day 1 of life. After G and N, the creatinine clearance of the neonates was decreased according to the dosage given to the mother. Whatever the aminoglycoside, kidneys presented proximal tubular alterations (close to those observed in adults) at protonic microscopy and, with electron microscopy, some modifications of distal tubules and of mature and immature glomeruli. It is concluded that the developing kidney can be altered after treating pregnant mothers with aminoglycosides. This model of in utero-induced nephrotoxicity is dose-dependent. Mature and/or immature structures could be affected. The toxicity of the investigated antibiotics could be asserted as G greater than or equal to N greater than A.
The effect of three aminoglycoside antibiotics--netilmicin (CAS 56391-57-2), gentamicin (CAS 1403-66-3) and amikacin (CAS 37517-28-5)--at subinhibitory concentrations (sub-MICs; 1/4 or 1/16 of the MICs) on the cytotoxic activity of Acinetobacter baumannii was studied. The cytotoxic factor was manifested by reduction of the number of isolated rat lung type II cells evaluated by alkaline phosphatase determination. All aminoglycosides at both concentrations studied (with the exception of 1/4 of the MIC of amikacin) did not modify cytotoxic activity of A. baumannii. This activity was partially inhibited only after treatment with amikacin at 1/4 of the MIC. In this case the number of type II cells after incubation with antibiotic treated A. baumannii was higher (71%) as compared to the number of type II cells cultured with untreated A. baumannii (47%).
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.
Escherichia coli is a leading cause of bacteraemia. The aim of this study was to evaluate all E. coli positive blood cultures collected during a 4-y period in a haematological department using piperacillin plus netilmicin for empiric treatment of febrile episodes. We measured the incidence of piperacillin-resistant E. coli bacteraemia among haematological and non-haematological patients, described the importance of previous antibiotic treatment for resistance development in E. coli and evaluated the impact of piperacillin resistance on the clinical outcome of E. coli bacteraemia. 114 episodes of E. coli bacteraemia in 104 patients were recorded and 98 episodes in 88 patients (42 males and 46 females) with a median age of 64 y (range 19-85 y) were evaluated. In 81.6% of the episodes the patients had a haematological disorder, dominated by acute leukaemia (41.3%), chronic leukaemia (16.3%) and lymphoma (10%). The proportion of piperacillin-resistant E. coli was higher among haematological patients than non-haematological patients (25% vs 0%, p=0.02) and resistance was associated with piperacillin therapy during the previous month (p=0.05). No difference in clinical outcome was found between haematological patients infected with piperacillin-susceptible or -resistant E. coli (intensive care 12% vs 15%; mortality 22% vs 25%).
Six antimicrobial agents were administered to 48 patients (divided in 6 groups) who underwent prostatectomy. Half of the patients received the antibiotic in a single dose one hour before the operation and the rest in divided doses 24 hours before the operation. The concentration levels in serum and in prostatic tissue were measured for each of the antibiotics and for each mode of administration. The obtained ratios of prostatic tissue to serum concentrations and the relative antimicrobial activity to local pathogens of each agent indicate that the agent of choice for prostatic disease is netilmicin followed by aztreonam, cefuroxime and the ticarcillin-clavulanic acid combination.
Studies of therapy for experimental pneumonia due to Pseudomonas aeruginosa have failed to document beta-lactam-aminoglycoside synergy for most antibiotics examined, in contrast to results usually observed with pseudomonas infections at other sites. The neutropenic guinea-pig model of pseudomonas pneumonia was modified to resemble more closely therapy for clinical infections. Animals were treated 16 hr after infection with ticarcillin, azlocillin, ceftazidime, tobramycin, and netilmicin, alone and in combination. As predicted by in vitro synergy testing, in all cases combination drug therapy was more effective than the corresponding drugs given alone (P less than .05), as assessed by quantitative lung culture. Among single-drug regimens, those in which peak antibiotic levels did not exceed the minimal bactericidal concentration for the organism were significantly less effective. Resistance to aminoglycosides did not develop during therapy, and therefore, in this study does not explain the mechanism of synergy observed with beta-lactam antibiotics.
An effort was made to elucidate the limits of drug-activity tests in small animals. Human plasma kinetics of gentamicin, netilmicin, ticarcillin, ceftazidime, and ceftriaxone were approximated in normal and in granulocytopenic mice infected with various strains of Pseudomonas aeruginosa in the thigh muscle or intraperitoneally. The effect of such dosing on bacterial time-kill curves and on survival was compared with the effect of identical amounts of drug given as a single-bolus injection. With beta-lactams, a highly significant superiority of fractionated dosing (simulated human kinetics) over bolus injections (murine plasma kinetics) was demonstrated, whereas with aminoglycosides it was a single-bolus injection that tended to be more active. Thus, when tested in conventional small-animal models, aminoglycoside activity may be overestimated, whereas beta-lactam activity may be underestimated in respect to humans. These differences found in vivo most probably reflect the different pharmacodynamics between aminoglycosides and beta-lactam drugs (time-kill curves, dose-response curves, and postantibiotic effect) similar to those previously observed in vitro.