In vitro synergy of ticarcillin/clavulanate in combination with aztreonam and ceftolozane/tazobactam against SPM-1-producing Pseudomonas aeruginosa strains.

Minimal inhibitory concentrations (MICs) of ticarcillin/clavulanic acid (TLc), ceftolozane/tazobactam (C/T), and aztreonam (AT) were determined for 6 SPM-1-producing Pseudomonas aeruginosa (PSA) using Etest® strips and the synergistic effect of such antimicrobials against was evaluated by gradient diffusion strip crossing (GDSC) test. The fraction inhibitory concentration indexes (FICI) were calculated and showed a synergistic (n = 3) and additive (n = 2) effects of TLc + AT against SPM-1 producers, while TLc + C/T combination caused no effect. Average MIC reduction of TLc and AT by GDSC was 3-fold and 2-fold dilutions, respectively. Thus, TLc + AT might be a candidate as a combination therapy to treat SPM-1-producing PSA infections.

Pharmacokinetics of ticarcillin-clavulanate in premature infants.

Ticarcillin-clavulanate covers a broad spectrum of pathogens that are common in premature infants. In infants <30 weeks gestational age, pharmacokinetic data to guide ticarcillin-clavulanate dosing are lacking. We enrolled 15 premature infants <30 weeks gestational age, determined pharmacokinetic parameters, and performed dosing simulations to determine optimal dosing for ticarcillin-clavulanate. The infants had a median (range) postnatal age (PNA) of 18 days (6-44 days) and gestational age of 25 weeks (23-28 weeks). Clearance was lower in infants with a PNA <14 days (0.050 L/kg/h [range 0.043-0.075]) compared with a PNA ≥14-45 days (0.078 L/kg/h [0.047-0.100]), consistent with maturation of renal function. Dosing simulations determined that ticarcillin 75 mg/kg q12h (PNA <14 days) or q8h (PNA ≥ 14-45 days) achieved the target exposure for organisms with a minimum inhibitory concentration ≤16 µ/mL in >90% of simulated infants. For highly resistant organisms (minimum inhibitory concentration 32 µg/mL), increased dosing frequency or extended infusion are necessary.

Oral Ambulatory Treatment of Acute Osteomyelitis in Children: A Case-Control Study.

The treatment of acute hematogenous osteomyelitis has evolved in recent years to a shorter parenteral treatment with an early switch to the oral route. Current publications recommend a 2- to 4-day parenteral treatment before the oral switch. We retrospectively analyzed a series of 45 children aged 1 to 11 years and treated in our department for acute osteomyelitis without severity criterion. Nineteen of 45 patients were treated by an exclusive ambulatory oral treatment by amoxicillin and clavulanic acid. Twenty six of 45 patients had a 2- to 4-day parenteral treatment before the oral switch. The minimum follow-up was 6 months. The primary endpoint was a clinical, radiographic, and biologic healing, 6 months after the beginning of the treatment. The secondary endpoints evaluated were the length of hospitalization, the total duration of treatment, and the type of antibiotic used. On the primary endpoint, we did not find any significant difference between the 2 treatments (P = 0.38). On the duration of treatment, we found a significant difference (P = 0.049) in favor of oral treatment. The ambulatory oral treatment by amoxicillin and clavulanic acid seems to be a valid alternative to the classical parenteral then oral sequence in the treatment of acute hematogenous osteomyelitis in children without severity criterion.

Tunable release of clavam from clavam stabilized gold nanoparticles--design, characterization and antimicrobial study.

A facile one-step approach is developed to synthesize highly stable (up to 6months) gold nanoparticles (GNPs) using Clavam, pharmaceutical form of amoxicillin which contains a mixture of amoxicillin and potassium salt of clavulanic acid, at room temperature (25-30°C). The clavam stabilized GNPs are characterized using various techniques including UV-Visible, FT-IR spectrophotometry and transmission electron microscopy (TEM). Tunable release of clavam from clavam stabilized GNPs is demonstrated using intracellular concentrations of glutathione (GSH). The process is monitored using an UV-Vis spectroscopy and the amount of clavam released in terms of amoxicillin concentration is quantitatively estimated using reverse phase high performance liquid chromatographic (RP-HPLC) technique. In vitro study reveals that the clavam released from GNPs' surface was found to show a significant enhancement in antibacterial activity against Escherichia coli and the cause of enhancement is addressed.

Stenotrophomonas maltophilia infection among young children in a cardiac intensive care unit: a single institution experience.

Stenotrophomonas maltophilia can present as bacteremia, respiratory tract infection, urinary tract infection, soft tissue and wound infections, bone and joint infections, meningitis, and endocarditis especially in immunosuppressed patients and those with underlying medical conditions. The incidence and impact of S. maltophilia in young children with heart disease are poorly defined. A single center retrospective observational study was conducted in infants <180 days of age with positive S. maltophilia cultures over a period of 5 years. The overall incidence for S. maltophilia infection was 0.8 % (n = 32/3656). Among 32 identified infants, there were 47 episodes of S. maltophilia infection 66 % of infants had prior exposure to broad spectrum antibiotics. 97 % of positive isolates were susceptible to trimethoprim/sulfamethoxazole and 91 % to levofloxacin as well as ticarcillin/clavulanate. Ventilator-free days and absolute lymphocyte count prior to acquiring infection were significantly lower in non-survivors than in survivors. 100 % of survivors had clearance of positive cultures compared to 50 % in non-survivors (p < 0.05). The crude all-cause mortality rate was 37.5 %. All non-survivors had increased length of ICU stay and duration of mechanical ventilation and had delayed clearance of infection and required longer duration of treatment.

Accumulation of amikacin in synovial fluid after regional limb perfusion of amikacin sulfate alone and in combination with ticarcillin/clavulanate in horses.

OBJECTIVES: To determine the effect of regional limb perfusion (RLP) with amikacin sulfate alone and in combination with ticarcillin/clavulanate on synovial fluid concentration and antimicrobial activity of amikacin. SAMPLE POPULATION: Experimental study. METHODS: RLP with amikacin alone (A; 2.5 g) or amikacin and ticarcillin/clavulanate (AT; 2.5 g amikacin, 7 g ticarcillin/clavulanate) was performed with a tourniquet placed at mid-antebrachium in standing, sedated horses. Perfusate blood was collected immediately after injection and again before tourniquet release. Blood from the jugular vein was collected before tourniquet release. Synovial fluid from the middle carpal joint was collected 0, 30, and 60 minutes after tourniquet release. Amikacin concentration and antimicrobial activity of synovial fluid against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa were determined. RESULTS: There was significantly lower amikacin concentration in the middle carpal joint synovial fluid of group AT compared with group A at 30 minutes (AT = median 4.4 µg/mL, IQR 3.0-11.2 µg/mL; A = 17.5 µg/mL, 6.6-80.1 µg/mL) and 60 minutes (AT = median 4.6 µg/mL, IQR 3.1-8.1 µg/mL; A = 15.0 µg/mL, 6.7-61.7 µg/mL) after tourniquet release. Zones of inhibition for ticarcillin-resistant Klebsiella pneumoniae from group AT were significantly smaller than group A from synovial fluid at 30 and 60 minutes after tourniquet release and in the perfusate serum before tourniquet release. CONCLUSIONS: The combination of amikacin with ticarcillin/clavulanate during RLP resulted in significantly lower amikacin synovial concentration and antimicrobial activity on amikacin susceptible and ticarcillin resistant cultures compared with amikacin alone.

Continuous infusion meropenem and ticarcillin-clavulanate in pediatric cystic fibrosis patients.

Aztreonam, cefepime, and ceftazidime are anti-pseudomonal beta-lactam antibiotics which have been previously reported to be administered by continuous infusion (CI) in pediatric CF patients. We present two cases administering intravenous (IV) meropenem and ticarcillin-clavulanate by CI in pediatric CF patients. The delivery of beta-lactam antibiotics via CI should be considered in order to optimize the pharmacodynamics (PD) of beta-lactams in the treatment of acute pulmonary exacerbations (APE).

Biological efficacy and stability of diluted ticarcillin-clavulanic acid in the topical treatment of Pseudomonas aeruginosa infections.

Topical compounded Timentin(®) diluted with an inactive vehicle has been reported to be effective in the treatment of otitis externa caused by Pseudomonas aeruginosa. The aims of this study were to determine the biological efficacy of Timentin(®) (ticarcillin and clavulanic acid) when diluted in the carrier vehicle Methopt(®) against P. aeruginosa and to determine the efficacy and stability of Timentin(®) aqueous stock concentrate solution. Timentin(®) stock concentrate was tested against four P. aeruginosa isolates on days 0, 7, 14, 21 and 28; then after 2, 3, 4, 5, 6, 9 and 12 months of storage at 4 or -20°C. The diluted Timentin(®)-Methopt(®) solutions were tested against all isolates after 0, 2, 4, 6, 8, 10, 12, 14, 17, 21, 24 and 28 days of storage at 24 or 4°C. Minimal inhibitory concentration (MIC) levels for all strains were determined using the broth microdilution method. The MIC of the stock solution remained relatively constant and acceptable throughout the study when stored at -20°C and was also acceptable for shorter time periods (6-9 months) when stored at 4°C. The MIC for the diluted Timentin(®)-Methopt(®) solution remained relatively constant and acceptable throughout the study for all four bacterial strains, with no difference between the solutions stored at 4 or 24°C. The results of this study indicate that storage of the Timentin(®) stock solution at -20°C does not compromise efficacy for at least 12 months and that Timentin(®) diluted in Methopt(®) was stable for 28 days when stored at either 4 or 24°C.

Population pharmacokinetic and pharmacodynamic modeling of high-dose intermittent ticarcillin-clavulanate administration in pediatric cystic fibrosis patients.

BACKGROUND: The Intermountain Cystic Fibrosis Pediatric Center utilizes ticarcillin-clavulanate 400 mg/kg/d divided every 6 hours, (maximum 24 g/d). This dosing strategy is higher than the Food and Drug Administration (FDA)-approved package labeling. We evaluated the microbiologic efficacy of this dosing regimen. OBJECTIVES: The primary study objective was to predict the pharmacokinetic (PK) and pharmacodynamic (PD) MIC breakpoints (the highest MIC with a probability of target attainment [PTA] of at least 90%) for the bacteriostatic and bactericidal targets of ticarcillin activity against Pseudomonas aeruginosa using the study dosing regimen. A secondary objective was to evaluate the tolerability profile of the higher ticarcillin-clavulanate dosing regimen in children with cystic fibrosis (CF). METHODS: This was a population-based PK-PD modeling study of pediatric CF patients admitted from January 1, 2005 to December 31, 2009 who received the dosing regimen for at least 7 days. Population PK and PD models were used to estimate PK and PD parameters for 127 clinically evaluable patients. A 10,000-patient Monte Carlo simulation was performed to estimate the target time in which free drug concentrations exceeded the MIC of the infecting organism. The 2 PK-PD targets of microbiologic efficacy included ≥30% for bacteriostasis and ≥50% for bactericidal effects of ticarcillin-clavulanate at higher than FDA-approved doses. RESULTS: A total of 127 patients (age, 0-19 years) met inclusion criteria. Serum concentration levels were modeled in this patient population using published PK parameters with intermittent ticarcillin peak concentrations reaching 288 (93.4) mg/L. The model predicted the PTA of the MICs for P. aeruginosa with a near-maximal bactericidal PK-PD MIC breakpoint of 16 µg/mL and a bacteriostasis PK-PD MIC breakpoint of 32 µg/mL. CONCLUSIONS: The results of our simulation suggest that in this select pediatric population, higher than FDA-approved doses of ticarcillin-clavulanate were effective in achieving bactericidal effects among pseudomonal isolates with MICs <16 µg/mL. Bacteriostatic and bactericidal effects were not frequently achieved among P. aeruginosa isolates with MICs >32 µg/mL. Additional studies are warranted to determine the clinical effectiveness of this dosing regimen.

High dose intermittent ticarcillin-clavulanate administration in pediatric cystic fibrosis patients.

BACKGROUND: The Intermountain Cystic Fibrosis Pediatric Center utilizes ticarcillin-clavulanate 400mg/kg/day divided every 6h, (maximum 24 g/day). This dosing strategy is higher than the Cystic Fibrosis Foundation (CFF) recommendations and the Food and Drug Administration (FDA) approved package labeling. The purpose is to determine the safety of this dosing regimen. METHODS: A retrospective study of pediatric cystic fibrosis (CF) patients admitted from January 1, 2005 to December 31, 2009 who received the dosing regimen for at least 7 days. Baseline and follow-up laboratory parameters were recorded. Statistical analysis was performed. RESULTS: 127 patients met inclusion criteria. The mean (+ or - SD) ticarcillin dose was 3.5 g (+ or - 2.16) every 6 h; while the mean (+ or - SD) total ticarcillin dose was 13.5 g (+ or - 6.5) per day. No significant differences occurred in liver function tests, white blood count, and platelet count from baseline. Serum creatinine showed a statistically significant decrease from baseline. CONCLUSIONS: Higher than FDA approved doses of ticarcillin-clavulanate may be safely used in the treatment of exacerbations in pediatric cystic fibrosis patients.

Antimicrobial delivery by intrasynovial catheterisation with systemic administration for equine synovial trauma and sepsis.

OBJECTIVE: To present the technique for intra-articular catheter placement and report the clinical outcomes of 38 cases of equine synovial trauma and/or infection treated with broad-spectrum antimicrobials administered via an intrasynovial catheter (ISC). DESIGN: Retrospective study. PROCEDURE: Medical records of 38 horses treated for synovial trauma and sepsis with frequent antimicrobial administration through an ISC from 1995 to 2008 were reviewed. Follow-up information was obtained via clinical re-evaluation or telephone contact with the owners. RESULTS: The majority of horses (84%) received amikacin and Timentin(R) four times daily. In addition, synovial lavage through the ISC was carried out in 27 horses (71%). Only radiological evidence of osteolysis had a significant negative impact on both lameness at the time of hospital discharge and the long-term outcome. In total, 92% of horses treated with frequent antimicrobial administration through an ISC had clinical resolution of infection. Catheter obstruction occurred in three cases, necessitating replacement or removal, and two synovial fistulae developed at sites of open drainage. The majority of horses treated had a favourable outcome, with 86% being at least pasture sound and 43% returned to riding. CONCLUSION: Septic synovial structures treated with frequent antimicrobial administration through an ISC had a good prognosis for survival and 43% returned to riding, which is consistent with the results of other studies. The use of a simple ISC should be considered when broad-spectrum intrasynovial antimicrobial administration and lavage of a septic synovial structure are indicated.

Second order Horner's syndrome in a cat.

This case report describes the clinical and magnetic resonance imaging (MRI) findings of a 3.5-year-old, male neutered, domestic shorthair cat with second order Horner's syndrome as the only clinical abnormality. The neuroanatomical pathway of the sympathetic innervation to the eye, differential diagnoses for Horner's syndrome in cats, and the interpretation of pharmacological testing are reviewed. The unusual MRI findings and the value of fat-suppressed MRI sequences are discussed.

Clavulanic acid stimulates sexual behaviour in male rats.

Sexual behaviour in rats can be used to predict putative effects on human sexual behaviour. Anecdotic reports exist, that the beta-lactamase inhibitor, clavulanic acid exerts sexual stimulating activities in monkeys. To characterize these pro-sexual activities, clavulanic acid was tested in three doses and compared to one dose of a sexually inhibitory dose of the selective serotonin reuptake inhibitor, paroxetine, in sexually-experienced male rats, selected for a moderate level of sexual performance in a standard 30-min test with an oestrus female. After acute administration, clavulanic acid had minor sexual stimulating effects at the highest dose in the number of intromissions and in the first ejaculation series. After sub-chronic 7-days treatment, clavulanic acid increased the number of ejaculations at all three doses and reduced the number of intromissions in the 1st series at the highest dose. After chronic 14 days treatment, a similar but stronger pro-sexual profile was observed. The sexual side effects of paroxetine were as expected, including slight sexual inhibitory effects after acute administration, but somewhat stronger overall inhibitory effects after 7 and 14-days pretreatment, particularly notable in the decreasing number of animals contributing to the 2nd ejaculation series, which was even stronger after 14-days treatment. One week after cessation of treatment, the paroxetine group had completely recovered, whereas the highest dose-group of clavulanic acid still showed some pro-sexual effects. This remarkable pro-sexual activity of clavulanic acid cannot readily be explained by its mechanism of action as a beta-lactamase inhibitor but could be due to unexpected central activity of the compound.

Continuous infusion of ticarcillin-clavulanate for home treatment of serious infections: clinical efficacy, safety, pharmacokinetics and pharmacodynamics.

Continuous infusion (CI) ticarcillin-clavulanate is a potential therapeutic improvement over conventional intermittent dosing because the major pharmacodynamic (PD) predictor of efficacy of beta-lactams is the time that free drug levels exceed the MIC. This study incorporated a 6-year retrospective arm evaluating efficacy and safety of CI ticarcillin-clavulanate in the home treatment of serious infections and a prospective arm additionally evaluating pharmacokinetics (PK) and PD. In the prospective arm, steady-state serum ticarcillin and clavulanate levels and MIC testing of significant pathogens were performed. One hundred and twelve patients (median age, 56 years) were treated with a CI dose of 9.3-12.4g/day and mean CI duration of 18.0 days. Infections treated included osteomyelitis (50 patients), septic arthritis (6), cellulitis (17), pulmonary infections (12), febrile neutropenia (7), vascular infections (7), intra-abdominal infections (2), and Gram-negative endocarditis (2); 91/112 (81%) of patients were cured, 14 (13%) had partial response and 7 (6%) failed therapy. Nine patients had PICC line complications and five patients had drug adverse events. Eighteen patients had prospective PK/PD assessment although only four patients had sufficient data for a full PK/PD evaluation (both serum steady-state drug levels and ticarcillin and clavulanate MICs from a bacteriological isolate), as this was difficult to obtain in home-based patients, particularly as serum clavulanate levels were found to deteriorate rapidly on storage. Three of four patients with matched PK/PD assessment had free drug levels exceeding the MIC of the pathogen. Home CI of ticarcillin-clavulanate is a safe, effective, convenient and practical therapy and is a therapeutic advance over traditional intermittent dosing when used in the home setting.

Clinical efficacy, tolerability, and cost savings associated with the use of open-label metronidazole plus ceftriaxone once daily compared with ticarcillin/clavulanate every 6 hours as empiric treatment for diabetic lower-extremity infections in older males.

BACKGROUND: Patients with diabetes mellitus, particularly those with poor glucose control, commonly experience various medical complications related to the disease (eg, renal impairment, decreased peripheral vascular circulation, suppressed immune function). Infections of the lower extremities can range from superficial cellulitis to ulcerative, deep soft-tissue infections to osteomyelitis that necessitates some degree of amputation. OBJECTIVE: This study compared the efficacy, tolerability, and cost differences associated with the use of metronidazole plus ceftriaxone (MTZ/CTX) given once daily with those of ticarcillin/clavulanate potassium (T/C) given every 6 hours in hospitalized older males with diabetic lower-extremity infections. METHODS: This prospective, open-label study was conducted at a Veterans Affairs Medical Center. Male patients with diabetes and a lower-extremity infection were randomized to receive MTZ/CTX 1 g once daily or T/C 3.1 g every 6 hours. Treatment success was determined at 96 hours or on discontinuation of antibiotic. Success was measured in terms of body temperature <38.3 degrees C (100.6 degrees F), normalization of the finger-stick blood sugar concentration, improvement in wound staging, or a white blood cell count <10,000 cells/mm3. Medication acquisition costs per treatment arm were calculated and compared. RESULTS: Seventy patients were enrolled in the study (36 MTZ/CTX, 34 T/C). The study population had a mean (SD) age of 63.8 (10.8) years, a duration of diabetes of 12.4 (9.1) years, 0.5 (0.7) diabetes-related comorbidities, and an initial creatinine clearance of 67.1 (26.0) mL/min. There were no significant differences between groups at randomization. At 96 hours, treatment success was achieved in 31 (86%) patients in the MTZ/CTX group, compared with 28 (82%) patients in the T/C group (P=NS). Twenty-six patients were considered successfully treated on the final day of therapy in both the MTZ/CTX group (72%) and the T/C group (76%) (P=NS). There were no significant differences in primary or secondary measures of success between the 2 groups. No single or multiple baseline factors predicted treatment success or failure. No patient experienced adverse events considered related to study medication. MTZ/CTX was associated with savings of $61.06 per hospital admission, or $2198.05 for all patients who received this combination. CONCLUSION: In this population of older males, once-daily MTZ/CTX was as well tolerated and effective as T/C in the treatment of diabetic lower-extremity infections and was associated with reduced institutional costs.

Three-day intravenous triple therapy is not effective for the eradication of Helicobacter pylori infection in patients with bleeding gastro-duodenal ulcer.

AIM: To test the efficacy of an ultra-short intravenous triple therapy against Helicobacter pylori infection in patients with bleeding peptic ulcer against standard oral 1-week triple therapy in a randomised, double-blind prospective trial. PATIENTS: (n = 75) with haemorrhagic peptic ulcer and H. pylori infection were randomised into: an Intravenous Group to receive omeprazole, clarithromycin and amoxicillin-clavulanic acid intravenously b.d. for 3 days followed by 7 days of oral omeprazole plus placebo of clarithromycin and amoxicillin; an Oral Group to receive intravenous omeprazole plus placebo of clarithromycin and amoxicillin-clavulanic acid followed by 7 days of oral omeprazole, clarithromycin and amoxicillin b.d. Gastric biopsies were obtained for urease test. A 13C-urea breath test was performed to check for H. pylori eradication. RESULTS: Intention-to-treat eradication was 50% (19/38) in the Intravenous Group and 78% (29/37) in the Oral Group (odds ratio 3.63; 95% confidence interval 1.32-9.94; P < 0.01; number needed to treat (NNT) = 4). Per protocol eradication was 50% (14/28) in the Intravenous Group and 86% (24/28) in the Oral Group (P < 0.005). There were no statistically significant differences in adverse events between the two treatment groups. CONCLUSIONS: An ultra-short, 3-day, intravenous, triple therapy containing omeprazole, clarithromycin and amoxicillin-clavulanic acid cannot be recommended as an effective eradication regimen for H. pylori infection related to haemorrhagic gastro-duodenal ulcer.

Evaluation of ticarcillin/clavulanic acid versus ceftriaxone plus amikacin for fever and neutropenia in pediatric patients with leukemia and lymphoma.

BACKGROUND: The empirical use of antibiotic treatments is widely accepted as a means to treat cancer patients in chemotherapy who have fever and neutropenia. Intravenous monotherapy, with broad spectrum antibiotics, of patients with a high risk of complications is a possible alternative. METHODS: We conducted a prospective open-label, randomized study of patients with lymphoma or leukemia who had fever and neutropenia during chemotherapy. Patients received either monotherapy with ticarcillin/clavulanic acid (T) or ceftriaxone plus amikacin (C+A). RESULTS: Seventy patients who presented 136 episodes were evaluated, 68 in each arm of the study. The mean neutrophil counts at admission were 217cells/mm(3) (T) and 201cells/mm(3) (C+A). The mean duration of neutropenia was 8.7 days (T) and 7.6 days (C+A). Treatment was successful without the need for modifications in 71% of the episodes in the T group and 81% in the C+A group (p=0.23). Treatment was considered to have failed because of death in two episodes (3%) in the T group and three episodes (4%) in the C+A group, and because of a change in the drug applied in one episode in the T group and two episodes in the C+A group. Overall success was 96% (T) and 93% (C+A). Adverse events that occurred in group T were not related to the drugs used in this study. CONCLUSION: In pediatric and adolescent patients with leukemia or lymphoma, who presented with fever and neutropenia, during chemotherapy, ticarcillin/clavulanic acid was as successful as the combination of ceftriaxone plus amikacin. It should be considered an appropriate option for this group of patients at high risk for infections.

Application of MEKC for determination of ticarcillin and clavulanic acid in Timentin intravenous preparation.

A micellar electrokinetic chromatography method for simultaneous assay of ticarcillin and clavulanic acid in Timentin i.v. injection preparation was developed. This method ensures excellent separation of both components of Timentin preparation. The validation of the method was performed, and specificity, reproducibility, precision and accuracy were confirmed. The detection and quantitative limits for Timentin were established in the concentrations 0.04 and 0.08 mg/ml, respectively. The elaborated technique was compared with two methods routinely used-UV and high performance liquid chromatography (HPLC). The obtained results and their statistical analysis proved the same precision of all methods, however, no significant differences were observed between CE and HPLC.

Ticarcillin-clavulanic acid plus amikacin versus ceftazidime plus amikacin in the empirical treatment of fever in acute leukemia: a prospective randomized trial.

We evaluated the efficacy of ticarcillin-clavulanic acid plus amikacin (TCA) with ceftazidime plus amikacin (CFA) as empiric therapy of fever in acute leukemia in a total of 127 episodes. The overall success rate of the therapy (survival) was 93% in TCA group and 92% in CFA group. Success without therapy modifications (afebrile at 72 hours) was 39% for TCA, 31% for CFA; success with modifications was 55% and 61% respectively. Failure (death due to documented or presumed infection) was 6% for TCA and 8% for CFA. Differences were not statistically significant. The success without modifications was higher in the group of patients with fever of unknown origin (FUO) than in documented infections (DI), mainly with CFA. No differences were documented in the resistance rate and in clinical outcome during severe neutropenia (ANC <100 microl). In our experience TCA is as effective as CFA as first-line treatment in severe neutropenic patients with acute leukemia, although in both regimens patients with DI are likely to require modifications in treatment.