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PubMed1987

Amikacin plus ceftazidime versus amikacin plus piperacillin versus amikacin plus aztreonam in infections in neoplastic patients with granulocytopenia.

Sixty granulocytopenic patients (granulocytes less than 1000/mm3) affected with solid tumors, previously submitted to antiblastic therapy and with infections, were treated with three antibiotic combinations: amikacin + ceftazidime, amikacin + piperacillin or amikacin + aztreonam. In 68% of the cases the infections were due to gram-negative and in the remaining 32% to gram-positive microorganisms. The results obtained with the three treatments show a slight but significant statistical difference (p less than 0.05), due to the greater efficacy of the amikacin + ceftazidime combination on gram-positive and amikacin + aztreonam on gram-negative bacteria.

Adult↗
PubMed1995

Piperacillin-tazobactam plus amikacin versus ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer.

Gram-positive bacteria have become the predominant infecting organisms in granulocytopenic cancer patients. Empiric antibiotic regimens used in febrile neutropenic patients often include an extended-spectrum cephalosporin, but the response to therapy in gram-positive coccal bacteremia has been unsatisfactory. Thus, new antibiotics with better activity against gram-positive bacteria should be tested. The objective of this prospective randomized controlled study was to evaluate and compare the efficacy and tolerance of piperacillintazobactam plus amikacin with that of ceftazidime plus amikacin, the standard regimen of the International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer, in the empiric treatment of febrile granulocytopenic cancer patients. A total of 858 episodes were eligible for this study, and 706 episodes were assessable for efficacy. The antibiotic treatment was successful in 210 (61%) of 342 episodes in the piperacillin-tazobactam-amikacin group compared with 196 (54%) of 364 episodes treated with ceftazidime plus amikacin (P = 0.05). The time to defervescence was significantly shorter (P = 0.01) and the time to failure was significantly longer (P = 0.02) in the piperacillin-tazobactam-amikacin group. A significant difference in response to bacteremic infections between the two patient groups was found: piperacillin-tazobactam plus amikacin was successful in 40 of 80 episodes (50%), and ceftazidime plus amikacin was successful in 35 of 101 episodes (35%) (P = 0.05). A multivariate analysis showed that the probability of failure was significantly greater with ceftazidime plus amikacin than with piperacillin-tazobactam plus amikacin (P = 0.02). This trial suggests that piperacillin-tazobactam plus amikacin is more effective than ceftazidime plus amikacin for the empiric treatment of fever and bacteremia in granulocytopenic cancer patients. Although cutaneous reaction was more frequently associated with piperacillin-tazobactam plus amikacin than with ceftazidime-amikacin, this unwanted effect was relatively mild and its incidence was comparable to that of other penicillin compounds.

Adolescent↗
PubMed2002

Cefepime plus amikacin versus piperacillin-tazobactam plus amikacin for initial antibiotic therapy in haematology patients with febrile neutropenia: results of an open, randomized, multicentre trial.

BACKGROUND: Standard therapy for suspected infections in patients with profound neutropenia is the combination of a beta-lactam antibiotic plus an aminoglycoside. Cefepime's broad-spectrum activity makes it an option for initial empirical therapy in neutropenic patients. The aim of this study is to evaluate the efficacy and safety of cefepime plus amikacin compared with piperacillin-tazobactam plus amikacin for initial empirical treatment of fever in adult haematology patients with severe neutropenia. METHODS: In this prospective multicentre trial, 969 patients with 984 febrile neutropenic episodes were randomized to receive iv amikacin (20 mg/kg every 24 h) combined with either cefepime (2 g every 8 h) or piperacillin-tazobactam (4 g/500 mg every 6 h). Clinical response was determined at 72 h and at completion of therapy. RESULTS: Eight hundred and sixty-seven episodes were assessable for efficacy (432 cefepime, 435 piperacillin-tazobactam). The frequency of success without modification of the empirical therapy was nearly identical for cefepime plus amikacin (49%) compared with piperacillin-tazobactam plus amikacin (51%). Similar rates of success were found for microbiologically documented infection: 40% versus 39%, respectively. Antibiotic modification was necessary in 49% of cefepime and 44% of piperacillin-tazobactam patients. The overall response rate, with or without modification of the assigned treatment, was 94% in both groups. Drug-related adverse events were reported in 10% of cefepime plus amikacin versus 11% of piperacillin-tazobactam plus amikacin patients. Mortality due to infection occurred in a total of 10 patients (two cefepime, eight piperacillin-tazobactam). CONCLUSION: The empirical regimen of cefepime plus amikacin is equivalent to piperacillin-tazobactam plus amikacin in febrile adult haematology patients with severe neutropenia. KEYWORDS: cefepime, piperacillin-tazobactam, amikacin, empirical antibiotic therapy, febrile neutropenia, haematological malignancy

Adult↗
PubMed1997

Once daily ceftriaxone plus amikacin vs. three times daily ceftazidime plus amikacin for treatment of febrile neutropenic children with cancer. Writing Committee for the International Collaboration on Antimicrobial Treatment of Febrile Neutropenia in Children.

BACKGROUND: The combination of ceftazidime plus aminoglycoside is widely used for the treatment of febrile neutropenic patients but requires multiple daily administration. Because the frequency of Pseudomonas aeruginosa is low in many centers, there is a rationale to test other antibiotic regimens that provide appropriate antibacterial coverage with the advantage of reduced dosing frequency, such as once daily ceftriaxone plus amikacin. METHODS: Febrile neutropenic children with leukemia, lymphoma or solid tumors after chemotherapy were included in an open, prospective, randomized, multinational study comparing once daily ceftriaxone plus amikacin vs. 8-hourly ceftazidime and amikacin. The response to antimicrobial therapy was defined as complete response, improvement or failure. Assessment of adverse events was supplemented by specific definitions of nephrotoxicity, ototoxicity, hepatotoxicity and hypokalemia. Costs were estimated from published values of acquisition costs, delivery costs and hospitalization costs. RESULTS: Efficacy was evaluable in 364 of 468 episodes in 265 children. Response rates in ceftriaxone and amikacin vs. ceftazidime and amikacin-treated episodes were 119 of 181 (66%) vs. 121 of 183 (66%), 7 of 181 (4%) vs. 9 of 183 (5%) and 55 of 181 (30%) vs. 53 of 181 (29%) for complete response, improvement and failure, respectively. Safety profiles were similar with both treatment regimens. The acquisition and administration costs were lower for the ceftriaxone and amikacin regimen. CONCLUSIONS: A once daily regimen of ceftriaxone and amikacin is as safe and clinically effective as that of three times daily ceftazidime and amikacin for the treatment of febrile neutropenic children with cancer and is more cost-effective. The once daily regimen of ceftriaxone and amikacin is suitable for outpatient treatment.

Adolescent↗
PubMed1993

Efficacy and toxicity of single daily doses of amikacin and ceftriaxone versus multiple daily doses of amikacin and ceftazidime for infection in patients with cancer and granulocytopenia. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer.

OBJECTIVE: To compare the efficacy and toxicity of single daily dosing of amikacin and ceftriaxone with that of multiple daily dosing of amikacin and ceftazidime for febrile episodes in patients with cancer and granulocytopenia. DESIGN: A prospective, randomized, unblinded, multicenter trial. SETTING: Twenty-one tertiary care or university medical centers. PATIENTS: Six hundred seventy-seven patients with cancer and granulocytopenia (858 febrile episodes). INTERVENTIONS: Random assignment to empiric therapy with a single daily dose of amikacin (20 mg/kg) and ceftriaxone (adults, 30 mg/kg; children, 80 mg/kg) (24-hour group) or with multiple daily doses of amikacin (6.5 mg/kg every 8 hours) and ceftazidime (33 mg/kg every 8 hours) (8-hour group). MEASUREMENTS: Percentage response to each regimen and occurrence of nephrotoxicity and ototoxicity. RESULTS: Single daily dosing of amikacin and ceftriaxone was as effective as multiple daily dosing of amikacin and ceftazidime (71% compared with 74%; difference, -3%; 95% Cl, -10% to 3%; P > 0.2). Equivalent responses also were noted for each category of infection. Median peak (30 minutes after a 60-minute infusion) serum concentrations of amikacin were higher in the 24-hour group than in the 8-hour group (45.6 compared with 21 micrograms/mL, P < 0.001), whereas trough (preinfusion) levels were lower (0.9 compared with 2 micrograms/mL, P < 0.001). Nephrotoxicity was 3% in the 24-hour group and 2% in the 8-hour group (difference, 1%; Cl, -1% to 4%). Increases in serum creatinine, however, were delayed (P = 0.048) and smaller (P = 0.06) in the 24-hour group than in the 8-hour group and occurred almost exclusively after other nephrotoxic drugs were added. Audiometry was only done in 144 patients (21%). Ototoxicity was 9% in the 24-hour group and 7% in the 8-hour group (difference, 2%; Cl, -7% to 11%; P > 0.2). Further infections developed in 15% and 12% of patients, respectively (difference, 3%; Cl, -2% to 9%). The overall mortality rate was 11% in both treatment groups (difference, 0%; Cl, -5% to 5%). CONCLUSIONS: Single daily dosing of amikacin and ceftriaxone was as effective and no more toxic than multiple daily dosing of amikacin and ceftazidime for the empiric therapy of infection in patients with cancer and granulocytopenia.

Adolescent↗
PubMed1982

Piperacillin plus amikacin therapy v carbenicillin plus amikacin therapy in febrile, granulocytopenic patients.

In a prospective randomized trial, febrile, granulocytopenic patients received either piperacillin sodium plus amikacin sulfate or carbenicillin disodium plus amikacin as initial empiric antimicrobial therapy. Although significantly more gram-negative aerobic bacilli isolated from initial cultures were susceptible to piperacillin than to carbenicillin (54 of 58 v 30 of 58), the overall response rates for the two regimens were similar (113 of 143 or 79% for piperacillin plus amikacin and 116 of 154 or 75% for carbenicillin plus amikacin). Piperacillin plus amikacin was associated with less hypokalemia (26 of 143 v 56 of 154). Nephrotoxicity, which was minimal with both regimens, developed less frequently in patients receiving carbenicillin plus amikacin (12 of 143 v two of 154). These results suggest that the overall efficacy of piperacillin plus amikacin is similar to carbenicillin plus amikacin and that piperacillin plus amikacin may be associated with less hypokalemia but more nephrotoxicity.

Adolescent↗
PubMed1988

Vancomycin, ticarcillin, and amikacin compared with ticarcillin-clavulanate and amikacin in the empirical treatment of febrile, neutropenic children with cancer.

We assessed two antibiotic regimens--vancomycin, ticarcillin, and amikacin, as compared with a vancomycin placebo, ticarcillin-clavulanate, and amikacin--as initial empirical therapy for febrile, neutropenic children with cancer. In a randomized, double-blind clinical trial, the planned 10-day treatment was unsuccessful in 15 percent of the vancomycin, ticarcillin, and amikacin group (n = 53), as compared with 38 percent of the group receiving ticarcillin-clavulanate and amikacin (n = 48) (P = 0.010). Of 10 episodes of breakthrough bacteremia, 9 (1 fatal) occurred in patients treated with ticarcillin-clavulanate and amikacin (P = 0.006). Each of the 10 microbial isolates was a gram-positive bacterium with similar susceptibilities to vancomycin and ticarcillin-clavulanate in vitro. Both regimens were well tolerated. None of the patients had detectable renal dysfunction, but those receiving vancomycin, ticarcillin, and amikacin were more likely to have twofold increases in serum hepatic-enzyme activity. Rashes consistent with the "red-man" syndrome occurred in three patients upon the infusion of vancomycin and in three others who received a placebo. We conclude that the combination of vancomycin, ticarcillin, and amikacin is more effective than ticarcillin-clavulanate and amikacin as empirical antibiotic therapy in clinical settings in which gram-positive bacteremias are a serious problem.

Adolescent↗
PubMed1986

Serum bactericidal activity and killing rate for volunteers receiving imipenem, imipenem plus amikacin, and ceftazidime plus amikacin against Pseudomonas aeruginosa.

Serum bactericidal activity against 20 strains of Pseudomonas aeruginosa was studied in 10 volunteers after administration of imipenem (25 mg/kg), imipenem (25 mg/kg) plus amikacin (7.5 mg/kg), and ceftazidime (25 mg/kg) plus amikacin (7.5 mg/kg). Eight strains were susceptible and 12 were resistant to ticarcillin. Serum levels were measured microbiologically after 30 and 60 min and were, respectively, 97 and 46 micrograms/ml for imipenem given alone and 79 and 45 micrograms/ml for imipenem given with amikacin. Despite the very large dose of imipenem used, imipenem and imipenem plus amikacin appeared slightly less active than ceftazidime plus amikacin (P less than or equal to 0.1; Wilcoxon matched-pairs test), with respective median titers at 30 min of 1:128, 1:128, and 1:256 against ticarcillin-susceptible strains and 1:32, 1:32, and 1:64 against ticarcillin-resistant strains; however, more than 90% of the serum determinations, regardless of the regimen, had a serum bactericidal activity greater than or equal to 1:8. Amikacin significantly increased the rate of killing in serum of P. aeruginosa by imipenem. Imipenem plus amikacin appeared as effective as ceftazidime plus amikacin in reducing the viable counts of P. aeruginosa after 24 h of incubation.

Amikacin↗
PubMed1992

Increased resistance to amikacin in a neonatal unit following intensive amikacin usage.

Gram-negative isolates from blood and cerebrospinal fluid were monitored for 1 year before and for 1 year after the first-line aminoglycoside in a busy pediatric department was changed from gentamicin to amikacin. In the general pediatric wards, the switch to amikacin resulted in no change in resistance of nosocomial gram-negative infections to either amikacin (0% before and after) or gentamicin (23.9% [before] versus 26.5% [after]). In the neonatal unit, the switch to amikacin was followed by an outbreak of Serratia spp. that were commonly resistant to amikacin but susceptible to gentamicin. This outbreak abated spontaneously. In the year after the change in aminoglycoside usage, the resistance to amikacin of nosocomially acquired gram-negative infections increased from 7.6 to 27.7% (P less than 0.001), and the resistance to gentamicin decreased from 71.2 to 60.2% (P = 0.07). The increase in amikacin resistance of gram-negative bacilli other than Serratia spp. has persisted for more than a year after the introduction of amikacin as the sole aminoglycoside. The different effects observed in the two sections of the pediatric department may be related to the more intensive usage of aminoglycosides in the neonatal unit.

Amikacin↗
PubMed1989

Analysis of amikacin-resistant Pseudomonas aeruginosa developing in patients receiving amikacin.

During a 36-month period, 28 patients treated for infections due to amikacin-susceptible Pseudomonas aeruginosa subsequently developed infections or colonization with amikacin-resistant P aeruginosa at the same site. Eleven amikacin-susceptible/-resistant pairs of isolates were analyzed for aminoglycoside-inactivating enzymes, plasmid profiles, cellular proteins, outer membrane proteins (OMPs), lipopolysaccharide (LPS) profiles, and amikacin uptake. While clearly distinct from isolates of other patients, sensitive and resistant isolates from the same patients were indistinguishable in plasmid profile, LPS profiles, and OMPs. These results suggest that the resistant P aeruginosa isolates were derived from the sensitive isolates. None of the resistant isolates produced enzymes known to inactivate amikacin. In nine of 11 resistant isolates tested, transport of amikacin into P aeruginosa was reduced. A major mechanism of in vivo development of amikacin resistance in P aeruginosa is alteration in permeability to amikacin, but the aquisition of plasmids or changes in OMPs or LPS profile may not account for this phenomenon.

Amikacin↗
PubMed2000

High-level amikacin resistance in Pseudomonas aeruginosa associated with a 3'-phosphotransferase with high affinity for amikacin.

This work describes the characterization of the phosphotransferase enzymatic activity responsible for amikacin resistance in two clinical Pseudomona aeruginosa strains, isolated from a hospital that used amikacin as first-line aminoglycoside. Amikacin-resistant P. aeruginosa PA40 and PA43 (MIC: 128 mg/l) were shown to have APH activity with a substrate profile similar to that of APH(3')-VI. The enzyme from P. aeruginosa PA40 was purified to > 70% homogeneity. The Km of amikacin for this enzyme was 1.4 microM, the Vmax/Km ratio for amikacin was higher than for the other aminoglycosides tested and PCR and DNA sequencing ruled out the presence of aph(3')-IIps. Amikacin resistance in this strain was, therefore, associated with APH(3')-VI and the high affinity of this enzyme for amikacin could explain the high-level resistance that we observed.

Amikacin↗
PubMed1985

Amikacin-resistant gram-negative bacilli: correlation of occurrence with amikacin use.

The incidence of amikacin resistance among gram-negative bacilli isolated at the New York V.A. Medical Center increased from 2.0% to greater than 7% during an 18-month period from January 1980 to July 1981. This increase coincided with a threefold increase in amikacin use at this institution. The amikacin-resistant (AKR) isolates most frequently recovered in 1981 were species of Klebsiella, Serratia, and Pseudomonas. These organisms were recovered from multiple sites, including urine, sputum, wounds, blood, peritoneal fluid, and pleural fluid. The amikacin-modifying enzyme 6'-N-acetyltransferase was detected in 27 (67.5%) of 40 randomly selected AKR isolates. These data indicate that resistance to amikacin in this hospital is enzymatically mediated in most strains of AKR Klebsiella and Serratia and in about one-third of AKR strains of P. aeruginosa. This finding supports the conclusion that amikacin resistance is enhanced by the pressure of increased amikacin use.

Acetyltransferases↗
PubMed2001

Single-daily ceftriaxone plus amikacin versus thrice-daily ceftazidime plus amikacin as empirical treatment of febrile neutropenia in children with cancer.

OBJECTIVE: Empirical antibiotic treatment for febrile neutropenic patients has been the mainstay of treatment for many years. Beta-lactam antibiotics and aminoglycosides have been the most frequently used drug combination. The purpose of this study was to evaluate the efficacy, safety, tolerance and costs of single-daily ceftriaxone plus amikacin versus thrice-daily dose of ceftazidime plus amikacin. METHODOLOGY: One hundred and ninety-one episodes of fever and neutropenia in 128 patients from October 1997 to December 1998 were included in a prospective, open-label, single-centre study. Patients were randomly assigned to either treatment group and evaluated as successes or failures according to defined criteria. Daily assessments were made on all patients and all adverse events recorded. Univariate and multivariate analysis of outcomes and a cost analysis were carried out. RESULTS: There were 176 evaluable patient-episodes with 51.1% in the single-daily ceftriaxone-amikacin group and 48.9% in the ceftazidime-amikacin group. There were 50 positive blood cultures: 12 Gram-positive bacteria, 33 Gram-negative bacteria and five fungi. Pseudomonas aeruginosa (P. aeruginosa) accounted for 14% of total isolates. The overall success rate was 55.5% in the ceftriaxone group compared to 51.2% in the ceftazidime group (P = 0.56). Mean time to defervescence was 4.2 days in the single-daily group and 4.3 days in the thrice-daily group. There were nine infection-related deaths; five in the single-daily ceftriaxone group. The daily cost of the once-daily regime was 42 Malaysian Ringgit less than the thrice-daily regime. There was a low incidence of adverse effects in both groups, although ototoxicity was not evaluable. CONCLUSIONS: The once-daily regime of ceftriaxone plus amikacin was as effective as the 'standard' combination of thrice-daily ceftazidime and amikacin with no significant adverse effects in either group. The convenience and substantial cost benefit of the once-daily regime will be particularly useful in developing countries with limited health resources and in centres with a low prevalence of P. aeruginosa.

Adolescent↗
PubMed1992

Comparison of two antibiotic regimens (piperacillin plus amikacin versus ceftazidime plus amikacin) as empiric therapy for febrile neutropenic patients with cancer.

A total of 170 febrile episodes in neutropenic patients with cancer were randomly assigned to be treated with piperacillin-amikacin or ceftazidime-amikacin. The overall response rates were similar in both groups (68 and 65%, respectively). Response rates for clinically or microbiologically documented episodes were 54.5% for piperacillin-amikacin and 58.8% for ceftazidime-amikacin. Response rates for gram-negative bacillary infections were 65 and 73%, respectively. There was also no difference for gram-positive infections (31 and 50%, respectively). The toxicities were also comparable and consisted of skin rashes, hypokalemia, and diarrhea. Vancomycin was added if the fever persisted 72 h after the beginning of therapy; it increased the response rates to 94% when used with piperacillin-amikacin and 92% when used with ceftazidime plus amikacin. Our results suggest that the combinations show similar global efficacies in the treatment of febrile episodes in cancer patients.

Adult↗
PubMed1999

Comparative efficacies of liposomal amikacin (MiKasome) plus oxacillin versus conventional amikacin plus oxacillin in experimental endocarditis induced by Staphylococcus aureus: microbiological and echocardiographic analyses.

Optimal treatment strategies for serious infections caused by Staphylococcus aureus have not been fully characterized. The combination of a beta-lactam plus an aminoglycoside can act synergistically against S. aureus in vitro and in vivo. MiKasome, a new liposome-encapsulated formulation of conventional amikacin, significantly prolongs serum half-life (t1/2) and increases the area under the concentration-time curve (AUC) compared to free amikacin. Microbiologic efficacy and left ventricular function, as assessed by echocardiography, were compared in animals administered either oxacillin alone or oxacillin in combination with conventional amikacin or MiKasome in a rabbit model of experimental endocarditis due to S. aureus. In vitro, oxacillin, combined with either free amikacin or MiKasome, prevented the bacterial regrowth observed with aminoglycosides alone at 24 h of incubation. Rabbits with S. aureus endocarditis were treated with either oxacillin alone (50 mg/kg, given intramuscularly three times daily), oxacillin plus daily amikacin (27 mg/kg, given intravenously twice daily), or oxacillin plus intermittent MiKasome (160 mg/kg, given intravenously, a single dose on days 1 and 4). The oxacillin-alone dosage represents a subtherapeutic regimen against the infecting strain in the endocarditis model (L. Hirano and A. S. Bayer, Antimicrob. Agents Chemother. 35:685-690, 1991), thus allowing recognition of any enhanced bactericidal effects between oxacillin and either aminoglycoside formulation. Treatment was administered for either 3 or 6 days, and animals were sacrificed after each of these time points or at 5 days after a 6-day treatment course (to evaluate for posttherapy relapse). Left ventricular function was analyzed by utilizing serial transthoracic echocardiography during treatment and posttherapy by measurement of left ventricular fractional shortening. At all sacrifice times, both combination regimens significantly reduced S. aureus vegetation counts versus control counts (P < 0.05). In contrast, oxacillin alone did not significantly reduce S. aureus vegetation counts after 3 days of therapy. Furthermore, at this time point, the two combinations were significantly more effective than oxacillin alone (P < 0.05). All three regimens were effective in significantly decreasing bacterial counts in the myocardium during and after therapy compared to controls (P < 0.05). In kidney and spleen abscesses, all regimens significantly reduced bacterial counts during therapy (P < 0.0001); however, only the combination regimens prevented bacteriologic relapse in these organs posttherapy. By echocardiographic analysis, both combination regimens yielded a significant physiological benefit by maintaining normal left ventricular function during treatment and posttherapy compared with oxacillin alone (P < 0.001). These results suggest that the use of intermittent MiKasome (similar to daily conventional amikacin) enhances the in vivo bactericidal effects of oxacillin in a severe S. aureus infection model and preserves selected physiological functions in target end organs.

Amikacin↗
PubMed1995

[Piperacilline/tazobactam combination+amikacin versus ceftazidime+amikacin in patients with neutropenia and fever. An open multicenter study. Groupe d'étude des Aplasies Fébriles].

OBJECTIVES: To evaluate the toxicity and effectiveness of piperacillin+tazobactam and amikacin compared with a reference treatment with ceftazidime and amikacin given as first line therapy in neutropenic patients with fever. METHODS: A multicentric randomized trial was conducted in 222 adults who had fever (38 degrees C for > 3 h) during a period of aplasia (white cell count < 0.5.10(9)/l for 22.9 +/- 10.4 days) induced by chemotherapy for acute leukaemia (68.1%) or by bone marrow autograft for lymphoma, myeloma or solid tumour (30.3%). 109 patients were assigned to the piperacillin (12 g/d)/tazobactam (1.5 g/d)+amikacin group and 113 to the ceftazidime (3 g/d)+amikacin group. Evaluation criteria were the frequency of apyrexia after a 72-hour antibiotic regimen and major infectious events defined as death due to infection and severe infections causing a delay in the chemotherapy protocol. RESULTS: Data obtained in 188 patients who fulfilled all the protocol criteria were evaluated. The episode of fever was controlled better with the piperacillin/tazobactam+amikacin combination (apyrexia achieved in 60.6% of the patients vs 44.7% in the ceftazidime+amikacin group, p = 0.028) and there were fewer superinfections (23% vs 41% respectively, p < 0.008). Tolerance was similar in the two groups. In vitro, 56% of the strains resistant to piperacillin and isolated prior to treatment were sensitive to the piperacillin/tazobactam combination. Among the strains isolated (41 Gram-, 61 Gram+), 72% were sensitive to ceftazidime and 84% were sensitive to the piperacillin/tazobactam combination. There were 16 deaths due to infection (8.5%) with no difference according to antibiotic regimen. There was no difference in toxicity. CONCLUSION: Tolerance was similar in the two groups. A combined regimen of piperacillin/tazobactam can be proposed as first line treatment for neutropenic patients with fever.

Adult↗
PubMed1986

In vitro evaluations of amikacin: an assessment of the currently used methods of disk diffusion and dilution susceptibility, antimicrobial synergy, and the measurement of amikacin concentrations.

The amikacin antimicrobial susceptibility tests were reviewed and found to be acceptable for clinical laboratory use. The early change from the 10-micrograms to the 30-micrograms diagnostic disk concentrations has resulted in reasonable accuracy, according to data from surveys of the College of American Pathologists, and acceptable discrimination between susceptible and resistant microorganisms. Similarly, standardized dilution susceptibility methods have proven acceptable, but great care must be exercised to select an agar medium in which performance was evaluated by the criteria of the National Committee for Clinical Laboratory Standards. Breakpoint concentrations selected as susceptible for amikacin (equal to or less than 16 micrograms/ml) were based on infected patient pharmacokinetics and previously correlated with patient bacteriologic outcome. Amikacin serum levels have been accurately measured by numerous procedures, including gas-liquid chromatography, radioimmunoassay, radioenzymatic assay, bioassay, and latex agglutination tests. Recent surveys of the College of American Pathologists support the earlier suspicions of lower accuracy and specificity with the bioassay method. Care must be taken to rapidly and appropriately process specimens from patients receiving concurrent high doses of antipseudomonal penicillins because of documented inactivation of some aminoglycosides by these penicillins. Amikacin is less affected by these beta-lactams. Evaluations of the antibacterial activity of amikacin in combination with other antimicrobial agents, principally the beta-lactams, continue to show high rates of enhanced killing or synergy. Although the methods for assessment of synergy have not been standardized, remarkably favorable and similar results between laboratories have been reported.

Amikacin↗
PubMed1993

Once- versus twice-daily amikacin regimen: efficacy and safety in systemic gram-negative infections. Scandinavian Amikacin Once Daily Study Group.

Three hundred and sixteen patients with serious infections verified or suspected to be of Gram-negative aetiology were treated in an open, randomized, comparative multicentre study with amikacin 15 mg/kg/day given either as a single dose or in two divided doses at 12 h intervals. Two hundred patients were evaluated for efficacy and all 316 for safety. The efficacy of both dosage regimens was very good with a satisfactory clinical response in 90% of the patients. There were no significant differences between the two regimens regarding efficacy and safety. This was also confirmed in an analysis according to the principle of 'intention-to-treat' including all randomized patients. In 218 patients additional therapy, most commonly with piperacillin or ampicillin, was considered necessary. The mean peak serum concentration of amikacin was 40.9 mg/L in the once-daily group, which is 10 x MIC for most Gram-negative bacteria, compared to 24.4 mg/L in the twice-daily group, which is 6 x MIC. Mean trough serum concentrations after 24 h were 1.8 mg/L in the once-daily group and 3.1 mg/L after 12 h in the twice-daily group. These serum concentrations were often close to or just below the MICs of the isolated pathogens. Drug related adverse reactions were seen in 40 (13%) of the patients. Among the adverse reactions with possible or probable relation to amikacin were 20 nephrotoxic events, nine in the once-daily group and 11 in the twice-daily group. A multivariate analysis of selective causative factors and nephrotoxic events gave a low correlation for once- vs twice-daily amikacin therapy. Five ototoxic events were observed, three in the once-daily group and two in the twice-daily group. One patient in the once-daily group experienced nausea in connection with amikacin infusions.

Amikacin↗