Impact of aminoglycoside cycling in six tertiary intensive care units: prospective longitudinal interventional study.

AIM: To determine the effect of aminoglycoside cycling in six tertiary intensive care units (ICU) on the rates of sepsis, aminoglycoside resistance patterns, antibiotic consumption, and costs. METHODS: This was a prospective longitudinal interventional study that measured the effect of change from first-line gentamicin usage (February 2002-February 2003) to amikacin usage (February 2003-February 2004) on the aminoglycoside resistance patterns, number of patients with gram-negative bacteremia, consumption of antibiotics, and the cost of antimicrobial drugs in 6 tertiary care ICUs in Zagreb, Croatia. RESULTS: The change from first-line gentamicin to amikacin usage led to a decrease in the overall gentamicin resistance of gram-negative bacteria (GNB) from 42% to 26% (P<0.001; z-test of proportions) and netilmicin resistance from 33% to 20% (P<0.001), but amikacin resistance did not change significantly (P=0.462), except for Acinetobacter baumanni (P=0.014). Sepsis rate in ICUs was reduced from 3.6% to 2.2% (P<0.001; chi(2) test), with a decline in the number of nosocomial bloodstream infections from 55/100 patient-days to 26/100 patient-days (P=0.001, chi(2) test). Furthermore, amikacin use led to a 16% decrease in the overall antibiotic consumption and 0.1 euro/patient/d cost reduction. CONCLUSION: Exclusive use of amikacin significantly reduced the resistance of GNB isolates to gentamicin and netilmicin, the number of GNB nosocomial bacteremias, and the cost of total antibiotic usage in ICUs.

[Comparative clinical-economic analysis of antibiotic therapy in pyogenic inflammatory diseases of the lower extremities]. / Sravnitel'nyi kliniko-ékonomicheskii analiz programm antibiotikoterapii gnoino-vospalitel'nykh zabolevanii nizhnikh konechnostei.

A randomized comparative investigation was carried out in two equal groups of patients with pyo-inflammatory diseases of lower extremities (the total number 50 patients) in order to study effectiveness and tolerance to Netilmycin (1st group) and Gentamycin (2nd group) given in combination with Cefasolin. Clinical symptoms were estimated immediately after operation, in 3, 6 and 10-12 days after it. Bacteriological investigations were fulfilled immediately after operation, in 72 h and in 6-10 days after the beginning of antibacterial therapy. Clinical and biochemical investigations of blood were fulfilled before and in 10 days after the beginning of the treatment. Effectiveness of the treatment in the first group was 100%, in the second group--80%. In the second group the antibiotics were changed in 20% of cases and the average duration of hospitalization among the patients of this group was reliably longer that in the first group. The eradication rating of Netilmycin was higher than that of Gentamycin (25 strains from 25 and 20 from 25 respectively). Gentamycin had a pronounced nephrotoxic effect (elevation of the level of creatinin and urea of blood in dynamics by 21% and 32%), as compared with Netilmycin (9% and 3%). Total expenses to antibiotic therapy in the first group made up 97,650 rub, and in the second group 106,245 rub. Netilmycin in combination with Cefasolin was more effective for acute pyo-inflammatory diseases of lower extremities than a combination of Gentamycin with Cefasolin, it more rapidly resulted in reduction of clinical signs of inflammation, was better endured and more economical.

Cost-effectiveness of cefepime + netilmicin or ceftazidime + amikacin or meropenem monotherapy in febrile neutropenic children with malignancy in Turkey.

Infection remains the major cause of morbidity and mortality in immunocompromised children with malignancy. In addition, the economic impact of antibiotic treatment should always be evaluated, especially in developing countries. In our center between January 1998 and January 1999, 73 children with hematological malignancies [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML)]; 9 children with solid tumors (rhabdomyosarcoma, neuroblastoma) had 87 febrile neutropenic episodes (related to chemotherapy). These children were randomized prospectively into three treatment groups. The first group (n: 28) received cefepime plus netilmicin, while the second group (n: 29) was treated with ceftazidime plus amikacin and the third (n: 30) with meropenem as monotherapy. The aim of the study was to compare the success rates and cost of fourth generation cephalosporin plus aminoglycoside and monotherapy of meropenem with ceftazidime plus amikacin, which is the standard therapy for febrile neutropenia. Microbiologically documented infections were 29.9%, clinically documented infections were 9.2% and 60.9% of the febrile neutropenic episodes were considered to be FUO. Gram-positive microorganisms were the most commonly isolated agents from blood cultures [MRSA (Methicillin Resistant Staphylococcus aureus) in 6 patients and MSSA (Methicillin Sensitive Staphylococcus aureus) in 4 patients]. The success rates were 78.5%, 79.3% and 73.3 % for the 1st, 2nd and 3rd groups respectively. In 4 patients (4.5%) fever responded only to amphotericin-B therapy. There was no statistically significant difference between the three treatment regimens with respect to efficacy, safety and tolerance (chi2 test, p>0.05), but while the third and fourth generation cephalosporins + aminoglycosides were comparable for cost, the monotherapy regimen was the most expensive. The main determining factors for the choice of treatment of febrile neutropenic children, especially in a developing country, are cost, presence of indwelling catheter and the bacterial flora of the unit, as well as efficacy.

[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.

Cost-effectiveness of ceftazidime or imipenem/cilastatin versus ceftriaxone + aminoglycoside in the treatment of febrile episodes in neutropenic cancer patients in Germany.

A three-pronged cost-effectiveness analysis of the treatment of febrile episodes in neutropenic cancer patients was conducted. It included a review of 37 randomized, controlled studies in the MEDLINE and EMBASE databases (1980-1996). Clinical outcomes as well as costs of treatment with imipenem/cilastatin, ceftazidime and ceftriaxone + aminoglycoside were compared. Primary therapy and modification, respectively, were successful in 62 and 27% of patients treated with imipenem/cilastatin, in 56 and 31% with ceftazidime and in 41 and 13% with ceftriaxone + aminoglycoside. From the perspective of a 1,800-bed teaching hospital, the average overall cost per successfully treated patient was DM 7,475 with imipenem/cilastatin, DM 7,810 with ceftazidime and DM 8,963 with ceftriaxone + netilmicin (DM 1 = USD 0.56; 7/97). The costs for the German national economy were imipenem/cilastatin DM 23,828, ceftazidime DM 24,985 and ceftriaxone + netilmicin DM 29,838.

A randomized prospective comparison of oral levofloxacin plus intraperitoneal (IP) vancomycin and IP netromycin plus IP vancomycin as primary treatment of peritonitis complicating CAPD.

OBJECTIVE: To compare the therapeutic efficacy of daily oral levofloxacin plus intermittent intraperitoneal (IP) vancomycin (group 1) versus daily IP netromycin and intermittent IP vancomycin (group 2) in the primary treatment of peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD). DESIGN: A randomized multicenter prospective open-label comparative clinical study. SETTING: University and Hospital Authority hospitals in Hong Kong. PATIENTS: All CAPD patients who developed bacterial or culture-negative peritonitis beyond 28 days of a previous episode and without evidence of septicemia, associated tunnel infection, or known sensitivity to trial medications were accepted into the clinical trial. RESULTS: A total of 101 patients entered the trial. The primary cure rate was 74.5% for group 1 and 73.6% for group 2. Baseline culture results appeared to influence the clinical outcome: the primary cure rate for culture-negative, gram-positive, and gram-negative episodes was 83.3%, 78.6%, and 42.9% for group 1 and 69.1%, 76.9%, and 71.3% for group 2, respectively. The primary cure rate also varied considerably among individual centers and was particularly noticeable in group 1. In the latter group, it correlated closely with in vitro levofloxacin resistance which in turn correlated closely with previous exposure to fluoroquinolones. CONCLUSION: Oral levofloxacin in combination with intermittent IP vancomycin has comparable efficacy to IP netromycin combined with intermittent IP vancomycin as primary treatment in CAPD peritonitis, but is simpler and more cost-effective to administer. It may be recommended as primary therapy in centers with relatively low exposure and, therefore, low background resistance to fluoroquinolones.

Comparison of once-daily and thrice-daily netilmicin regimens in serious systemic infections: a multicenter study in six Asian countries.

Patients with serious systemic infections admitted to eight medical centers in six Asian countries were treated with 300 mg of netilmicin given once daily (group A: 92 patients) or 100 mg of netilmicin given three times daily (group B: 93 patients). Netilmicin was administered by intramuscular injection or slow intravenous infusion until clinical, laboratory, and bacteriologic measures were normalized and for not more than two additional days. A clinical cure was achieved in 88% of the patients from group A and in 68% from group B. The causative micro-organisms were eliminated or infection site healed in 90% of group A and in 88% of group B. The mean treatment duration was 6.9 days in group A and 8.8 days in group B. Two patients in each group developed symptoms of nephrotoxicity; the pretreatment serum creatinine levels in all four patients were in the high borderline range. No other serious side effects were found. It is concluded that netilmicin administered once daily is safe and more effective than netilmicin administered three times daily.

Valoración clínica y bacteriológica de netilmicina en niños con infecciones graves / Clinical and bacteriological evaluation of netilmicin in children with severe infections

Se realizó un estudio en 20 niños con infecciones graves y repercusión orgánica generalizada, para valorar la eficacia de netilmicina, nuevo agente aminoglucósido. En el estudio se incluyeron principalmente padecimentos del aparato respiratorio, del gastrointestinal y de tejidos blandos. Después de la identificación bacteriológicas y pruebas de sensibilidad a los antibióticos, se inició la administración de netilmicina a dosis de 6mg/kg/día, con rango de 9 a 100mg y una media de 27.8 mg, como dosis unitaria en tres aplicaciones diarias, por un periodo que varió de 7 a 12 días. La vía de administración fue tanto IM como IV. Durante el curso del estudio 17 pacientes mejoraron en forma importante, 8 de ellos con curación completa; 3 fallecieron, uno por pobre respuesta al tratamiento y 2 por la gravedad del padecimiento y patología concomitante de alto riesgo. La netilmicina se estudió por su menor toxicidad y por alcanzar mayor nivel sérico con menor toxicidad en comparación con gentamicina, aún cuando la seguridad de esta última es excelente

Netilmicin (Netromycin, Schering-Plough).

Netilmicin sulfate, the 1-N-ethyl derivative of sisomicin, is a new aminoglycoside recently released for use in Canada and not yet released in the U.S. Its place in therapeutics, compared with gentamicin (G), tobramycin (T), and amikacin (A), is not yet established. Preliminary work in animals has suggested a lower incidence of nephrotoxicity and ototoxicity than with other aminoglycosides, and in vitro work has suggested some activity against G/T-resistant organisms. However, netilmicin appears to be virtually identical to G,T, and A in antimicrobial spectrum (except for its poorer activity against P. aeruginosa), human toxicity, and clinical use. For G/T-resistant organisms, amikacin is still the aminoglycoside of choice. In summary, netilmicin has not been demonstrated to have significant advantages over other aminoglycosides (G,T,A), and it is more expensive; thus, its potential value is limited.

Pharmacokinetic assessment of netilmicin in newborns and older children.

The pharmacokinetics of netilmicin were analyzed in 30 children, including 13 premature and seven gestationally mature newborns. Ten were children ranging in age from 3.5 months to 13 years. The newborns exhibited more variation in serum levels than the older children, and the premature babies more than those born at term. The serum half-life (t1/2), tended to show higher values in premature than in mature newborns, although this was not statistically significant. The newborns had a t1/2 of 5.9 hours, compared to 2.5 hours in the older children. There was no statistically significant difference in distribution volumes or coefficients between the two groups of newborns who had an insignificantly higher relative apparent beta-phase distribution volume coefficient of 0.420 l/kg, compared to 0.377 l/kg in the older children. All had distribution coefficient values within the same range. The total body clearance in absolute terms, and when referred to body surface of 1.73 m2, was significantly lower in the newborns than in the older children, but the clearance, when referred to body weight, was of the same order in the babies and older children. The age differences affect dosage. Dosage schedules based on pharmacokinetics are proposed for gestationally premature babies, mature newborns, and older children. Premature infants can receive 2.5 mg/kg body weight and gestationally mature newborns 3.0 mgkg, both every 12 hours; the monitoring of serum concentrations is mandatory. Children aged three months and older can receive 3.0 mg/kg every eight hours.