netilmicin and Agranulocytosis

Efficacy of the cephalosporin, ceftriaxone, was compared with that of the combination of the aminoglycoside, netilmicin, and the penicillin, azlocillin, in the treatment of febrile episodes in immunocompromised neutropenic children undergoing chemotherapy for neoplastic disease. During 100 separate febrile episodes, 40 strains of bacteria were isolated from the blood of 34 patients and a further 55 strains from other sites. Nine strains (four of which were staphylococci) to both netilmicin and azlocillin. There was no difference in clinical response between the two therapeutic regimens as assessed 4 and 7 days after treatment began. Ceftriaxone had the considerable practical advantages of once daily dosage without a need for blood monitoring. Ceftriaxone would appear to be effective as initial monotherapy in the treatment of bacterial infections in severely neutropenic children.

Topics: Adolescent; Agranulocytosis; Azlocillin; Bacteria; Bacterial Infections; Ceftriaxone; Child; Child, Preschool; Fever; Humans; Infant; Neoplasms; Netilmicin; Neutropenia; Randomized Controlled Trials as Topic

A randomized study of treatment with ciprofloxacin combined with benzylpenicillin (CB) versus a standard regimen of netilmicin combined with piperacillin (NP) as first-line empiric therapy was conducted in febrile neutropenic patients. Ninety-six patients were evaluable for determination of efficacy: 50 patients received CB and 46 patients received NP. There was no significant difference between the two groups in terms of age or primary diagnosis. Overall clinical response rate at the end of therapy was 66 percent for CB and 65 percent for NP. Microbiologic assessment revealed more pathogens eradicated by CB (64 percent) and fewer persisting (4 percent) than in the NP group (52 percent eradicated, 13 percent persisting). Only 10 percent of patients in the CB group had treatment-related adverse reactions as opposed to 28 percent of the NP-treated patients; these were predominantly renal impairment and were likely to have been due to the aminoglycoside. Staphylococcus epidermidis was the most commonly isolated pathogen, accounting for 38 percent of all isolates and 30 percent of all patients in whom treatment failed. Although streptococci accounted for 18 percent of the isolated pathogens, no treatment failures or superinfections were due to these organisms. This indicates an advantage of combining ciprofloxacin with benzylpenicillin. We conclude that the CB regimen is as effective as the NP treatment and is associated with fewer side effects.

Topics: Adult; Agranulocytosis; Bacteria; Bacterial Infections; Ciprofloxacin; Drug Therapy, Combination; Fever; Humans; Infusions, Intravenous; Middle Aged; Netilmicin; Neutropenia; Penicillin G; Piperacillin; Random Allocation

To assess the efficacy of ciprofloxacin in neutropenic patients, we conducted a randomized prospective trial comparing the combination of ciprofloxacin and netilmicin against piperacillin plus netilmicin as an empiric treatment of fever in cancer patients with neutropenia. Of 214 evaluable episodes, 115 and 99 were randomly assigned to the ciprofloxacin and the piperacillin arms, respectively. The overall response rates were very similar (59 and 62% for the ciprofloxacin and piperacillin arms, respectively). The response for the gram-positive bacteremias was almost identical (around 40%); this low response was due in part to an outbreak of infection by a multiply resistant strain of Staphylococcus epidermidis (for which the ciprofloxacin MIC was greater than or equal to 128 micrograms/ml) which occurred during the second half of the trial. Among gram-negative bacteremias, 9 of 11 infections (82%) responded to the ciprofloxacin combination compared with 3 of 7 (43%) that responded to the piperacillin combination (P = 0.23). The incidences of persistent, profound neutropenia were comparable in both treatments, but the susceptibility of the gram-negative organism to ciprofloxacin and netilmicin was significantly higher than was susceptibility to the other combination. Ciprofloxacin was well tolerated, and patients were able to convert from intravenous to oral therapy in 64 of 115 episodes.

Topics: Administration, Oral; Adolescent; Adult; Aged; Agranulocytosis; Bacterial Infections; Bone Marrow Transplantation; Ciprofloxacin; Drug Therapy, Combination; Female; Fever; Humans; Infusions, Intravenous; Injections, Intravenous; Leukemia; Lymphoma; Male; Middle Aged; Netilmicin; Neutropenia; Piperacillin; Prospective Studies; Random Allocation

Ceftazidime in doses of 100 mg/kg/day was used, combined with netilmicin 6 mg/kg/day, as first-line treatment in two successive studies conducted on febrile neutropenic children (neutrophils less than 500/mm3). Study n. 1, performed at the Infantile Haematology unit of Saint Louis hospital, Paris, included 75 children. Study n. 2 was a multicentre study involving 88 children from 11 medical centres. The children's age in both studies ranged from 2 months to 16 1/2 years (mean 7 years). The percentage of bacteriologically documented febrile episodes was 45 per cent (34/75 and 39/88), and the most frequent infections were those caused by Gram-positive cocci (56 and 58 per cent respectively of the cases). Vancomycin 40 mg/kg/day was introduced if fever was still present 48 hours after the beginning of the antibiotic therapy. Effective treatments were continued until the neutropenia was corrected. These children were being treated for acute leukaemia, lymphoma, solid tumours or bone marrow aplasia. In study n. 1 apyrexia was obtained in 85 per cent of the cases with the ceftazidime-netilmicin combination and in 91 per cent of the cases after addition of vancomycin. The initial therapy was effective in all patients with a documented infection. There were tow super-infections with septicaemia: one due to Streptococcus D, the other to Staph. epidermidis. In study n. 2 73 per cent of the patients were apyretic after the first combination and 85 per cent after vancomycin was introduced. In proven infections the ceftazidime-netilmicin combination was effective in 30 cases and in another 6 cases after addition of vancomycin. Three patients remained febrile until they came out of aplasia. In all cases the bacterial cultures were sterilized by the ceftazidime-netilmicin combination. There was no superinfection. The mean duration of antibiotic therapy was 21 days in study n. 1 and 14 days in study n. 2. The drugs were perfectly tolerated both clinically and biochemically. No death occurred in the two studies. Thus, owing to its broad spectrum, effectiveness and safety ceftazidime is a very useful antibiotic when combined with netilmicin as first-line treatment of febrile neutropenic children.

Topics: Adolescent; Agranulocytosis; Bacterial Infections; Ceftazidime; Child; Child, Preschool; Clinical Trials as Topic; Drug Evaluation; Drug Therapy, Combination; Humans; Infant; Multicenter Studies as Topic; Netilmicin; Neutropenia

Over a two year period 174 evaluable episodes of fever in neutropenic patients were treated in a randomized study comparing four beta-lactam antibiotics, each given in combination with netilmicin. Exclusions included episodes due to viral or fungal infection, and trial violations. Most patients were receiving treatment for leukaemia, including 18% undergoing bone marrow transplantation. The overall response rate (EORTC criteria) was 66%, ranging from 56% for cefoperazone to 76% for mezlocillin. Microbial documentation was obtained in 31% of episodes; Gram-positive isolates were most frequent but Pseudomonas aeruginosa was found in 18 patients. In patients with microbiologically documented infection 70% improved, overall--from 40% with cefoperazone to 80% with piperacillin (P less than 0.05). Nephrotoxicity was seen in 6.7% and was associated with severe documented sepsis. Hypokalaemia was seen in 29% and was most marked in patients receiving ticarcillin. Rashes occurred in 6.6% overall, with no difference between the groups. Ototoxicity, shown by serial audiograms, was seen in 4.7% of patients. No evidence of vestibular dysfunction was seen in 62 patients studied. Of thirteen deaths due to the primary infection, seven were caused by Ps. aeruginosa and five by fungi.

Topics: Agranulocytosis; Anti-Bacterial Agents; Cefoperazone; Clinical Trials as Topic; Drug Therapy, Combination; Feces; Fever; Gram-Negative Bacteria; Humans; Mezlocillin; Microbial Sensitivity Tests; Netilmicin; Neutropenia; Piperacillin; Random Allocation; Respiratory System; Superinfection; Ticarcillin

Topics: Adult; Agranulocytosis; Amikacin; Bacterial Infections; beta-Lactamase Inhibitors; Child; Clavulanic Acids; Clinical Trials as Topic; Drug Therapy, Combination; Fever; Fever of Unknown Origin; Humans; Netilmicin; Neutropenia; Penicillins; Retrospective Studies; Sepsis; Ticarcillin; Tobramycin

During a randomized clinical trial comparing tobramycin plus ticarcillin to netilmicin plus ticarcillin as empiric therapy of febrile neutropenic patients, Staphylococcus epidermidis emerged as the predominate superinfecting pathogen in tobramycin recipients. Overall clinical response was 68% (44/65 responding) in tobramycin/ticarcillin recipients and 73% (45/62) in netilmicin/ticarcillin recipients. However, 5/65 tobramycin/ticarcillin treated episodes were complicated by bacteremic superinfection with Staphylococcus epidermidis, as compared to 0/62 netilmicin/ticarcillin treated episodes (p less than 0.05). Four of the five bacteremic strains produced aminoglycoside adenylating enzyme ANT 4', 4''. Prior colonization of patients with identical strains was demonstrated by plasmid profile analysis, antibiograms and biotyping with the API Staph-Ident system. During the trial, 36 consecutive patients were studied for colonization patterns with coagulase-negative staphylococci. S. epidermidis accounted for 566/831 (68%) isolates of coagulase-negative staphylococci recovered from surveillance cultures. Tobramycin-resistant strains were acquired in 2/17, 4/12 and 9/14 patients during trimethoprim/sulfamethoxazole, netilmicin/ticarcillin and tobramycin/ticarcillin therapy, respectively. Prior to aminoglycoside therapy, 77% of strains were susceptible to less than or equal to 8 micrograms/ml of tobramycin, but only 35% and 28% were susceptible to tobramycin after initiation of tobramycin/ticarcillin and netilmicin/ticarcillin therapy, respectively. In contrast, greater than or equal to 93% of isolates were susceptible to netilmicin before and after aminoglycoside therapy. Absence of several sites susceptible to modification by aminoglycoside inactivating enzymes produced by staphylococci may give netilmicin a therapeutic advantage in the therapy of febrile neutropenic patients.

Topics: Adult; Agranulocytosis; Aminoglycosides; Clinical Trials as Topic; Cross Infection; Drug Therapy, Combination; Ear; Humans; Kidney; Netilmicin; Neutropenia; Penicillin Resistance; Random Allocation; Sepsis; Staphylococcal Infections; Staphylococcus epidermidis; Ticarcillin; Tobramycin

Topics: Agranulocytosis; Amikacin; Aminoglycosides; Anti-Bacterial Agents; Drug Therapy, Combination; Gentamicins; Humans; Netilmicin; Neutropenia; Sepsis

For the treatment of febrile episodes in granulocytopenic cancer patients, a combination of bactericidal and intravenously administered broad spectrum agents is recommended. An aminoglycoside plus a beta-lactame (piperacillin, azlocillin or IIIrd generation cephalosporins) are the drugs of first choice in an empiric approach. Because of frequent parenteral interventions (e.g. catheters, cannulations) in thrombopenic patients with multifactorial immunosuppression, we consider the application of once daily drugs, such as ceftriaxone, netilmicin or amikacin. For single dose treatment (1st day two applications), we used ceftriaxone in combination with netilmicin or amikacin as the first approach and retrospectively evaluated 47 patients for efficacy and safety.

Topics: Adult; Agranulocytosis; Amikacin; Bacterial Infections; Ceftriaxone; Drug Therapy, Combination; Female; Fever; Humans; Male; Middle Aged; Neoplasms; Netilmicin; Retrospective Studies

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Agranulocytosis; Bacterial Infections; Drug Therapy, Combination; Humans; Middle Aged; Neoplasms; Netilmicin; Spiramycin

Sixty infections episodes in granulocytopenic patients have been treated in first line with a piperacillin and netilmicin combination. Treatment has been successful in 78% bacterial infections. So, this antibiotic combination appears as a very effective therapy of infection in neutropenic patients.

Topics: Adult; Aged; Agranulocytosis; Bacterial Infections; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Netilmicin; Piperacillin; Sepsis

Infection is the most important cause of mortality in leucopenic patients. A broad spectrum antibiotic therapy is imperative in febrile and neutropenic patients. In a multicentric study we have used ceftazidime (100 mg/kg/d) and netilmicin (6 mg/kg/d) in 88 children (fever greater than or equal to 38.5 degrees C, neutropenia less than 500/mm3) treated for acute leukemias (59), non Hodgkin lymphomas (13) or solid tumors (16). Median age was 7 years (2 months-16 years). In patients who continued to remain febrile, vancomycin (40 mg/kg/d) was added after 48 hours. The effective treatment was continued until a neutrophil count greater than 1,000/mm3. The first combination (ceftazidime + netilmicin) was effective in 64 children (73%) and the second combination (ceftazidime + netilmicin + vancomycin) in 11 patients. Bacteria were isolated in 39 children: Escherichia coli: 9, Staphylococcus epidermidis: 9, Staphylococcus aureus: 8, Streptococcus: 6, Pseudomonas aeruginosa: 3, Streptococcus pneumoniae: 1, Haemophilus: 1, Klebsiella pneumoniae: 1, Proteus: 1, Serratia: 1, Flavobacterium: 1. In these 39 patients, 30 became apyretic with ceftazidime and netilmicin and 6 after vancomycin. All blood culture were negative after the first combination. The median duration of antibiotic therapy was 14 days (5-9 days: 28, 10-20 days: 43, greater than 20 days: 17). There were no death, no superinfection. Tolerance was good without kidney or liver or biological perturbation. We conclude that the combination ceftazidime and netilmicin is effective in neutropenic children.

Topics: Adolescent; Agranulocytosis; Bacterial Infections; Ceftazidime; Child; Child, Preschool; Drug Therapy, Combination; Fever; Humans; Infant; Netilmicin; Neutropenia; Vancomycin

No preventive treatment other than intestinal decontamination with oral colimycin was given. Antibiotic therapy with piperacillin 200-300 mg/kg, netilmicin 6-7.5 mg/kg and cloxacillin 50-100 mg/kg was initiated within 6 to 12 hours of clinical onset, using a central catheter. Twenty-nine children with bone marrow aplasia and less than 1000 leucocytes/mm3 were treated: 20 had acute lymphoblastic leukaemia or lymphoma (first episode 13, relapse 7, including 3 undergoing bone marrow transplantation), 6 had acute myeloblastic leukaemia (first episode 4, relapse during transplantation 2), and there was 1 case each of idiopathic bone marrow aplasia, metastatic sympathico-blastoma and lymphohistiocytosis. Mean age was 9 years (range: 2-19 years). The combined antibiotic therapy was continued until recovery from aplasia in case of success and discontinued after 48 hours in case of failure. Bacteriological examinations were negative in 19 patients and positive in 10; 13 strains were isolated, mostly staphylococci and streptococci. Apyrexia was obtained in 24 patients, 11 of whom had a rise of temperature with negative bacteriology about 10 days later. There were 4 initial failures and one unassessable result. An atopic patient developed a skin rash on the 3rd day of treatment. There was no death, no superinfection and non clinical or biochemical side-effect. It is concluded that the piperacillin-netilmicin -cloxacillin combination, which gave a high success rate and was well tolerated, can be recommended in neutropenic children with febrile episodes.

Topics: Adolescent; Adult; Agranulocytosis; Bacterial Infections; Child; Child, Preschool; Cloxacillin; Drug Therapy, Combination; Fever; Humans; Netilmicin; Neutropenia; Piperacillin

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.

Topics: Agranulocytosis; Aminoglycosides; Animals; Anti-Bacterial Agents; Ceftazidime; Ceftriaxone; Female; Gentamicins; Humans; Metabolic Clearance Rate; Mice; Netilmicin; Peritonitis; Pseudomonas Infections; Ticarcillin

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.

Topics: Agranulocytosis; Aminoglycosides; Animals; Anti-Bacterial Agents; Azlocillin; Ceftazidime; Cephalosporins; Drug Synergism; Drug Therapy, Combination; Guinea Pigs; Netilmicin; Neutropenia; Penicillin Resistance; Penicillins; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Ticarcillin; Tobramycin

The efficacy of various dosage schedules of netilmicin against Pseudomonas aeruginosa has been compared using an in vivo model (normal and granulocytopenic mice). Bolus injections were at least as effective as simulated short infusions or simulated continuous infusions of identical total amounts of netilmicin.

Topics: Agranulocytosis; Animals; Delayed-Action Preparations; Disease Models, Animal; Gentamicins; Infusions, Parenteral; Injections, Intravenous; Mice; Netilmicin; Pseudomonas aeruginosa; Pseudomonas Infections

The incidence of auditory toxicity resulting from therapy with ticarcillin (T) (12 g/sq m/day) in combination with gentamicin (G) (200 mg/sq m/day), amikacin (A) (600 mg/dq m/day), or netilmicin (N) (280 mg/sq m/day) was compared. Before administration of these antibiotic combinations to febrile, granulocytopenic patients, baseline audiograms were determined by a pharmacist using a portable audiometer. The before-therapy audiograms for 32 patients receiving T and G, 29 receiving T and A, and 29 receiving T and N were compared with the audiograms after the completion of therapy. The mean length of therapy was seven days. Two patients (6.2%) receiving T and G, one (3.4%) receiving T and N, and one (3.4%) receiving T and A developed auditory toxicity with bilateral decreases of at least 20 decibels at one or more frequencies. The incidence of auditory toxicity secondary to aminoglycoside exposure was low, and the relative auditory toxicity among the three aminoglycosides appeared to be similar.

Topics: Agranulocytosis; Amikacin; Aminoglycosides; Anti-Bacterial Agents; Audiometry; Drug Therapy, Combination; Gentamicins; Hearing Disorders; Humans; Netilmicin; Ticarcillin