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.

Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis.

BACKGROUND: Cystic fibrosis is a genetic disorder in which abnormal mucus in the lungs is associated with susceptibility to persistent infection. Pulmonary exacerbations are when symptoms of infection become more severe. Antibiotics are an essential part of treatment for exacerbations and inhaled antibiotics may be used alone or in conjunction with oral antibiotics for milder exacerbations or with intravenous antibiotics for more severe infections. Inhaled antibiotics do not cause the same adverse effects as intravenous antibiotics and may prove an alternative in people with poor access to their veins. This is an update of a previously published review. OBJECTIVES: To determine if treatment of pulmonary exacerbations with inhaled antibiotics in people with cystic fibrosis improves their quality of life, reduces time off school or work and improves their long-term survival. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Group's Cystic Fibrosis Trials Register. Date of the last search: 03 October 2018.We searched ClinicalTrials.gov, the Australia and New Zealand Clinical Trials Registry and WHO ICTRP for relevant trials. Date of last search: 09 October 2018. SELECTION CRITERIA: Randomised controlled trials in people with cystic fibrosis with a pulmonary exacerbation in whom treatment with inhaled antibiotics was compared to placebo, standard treatment or another inhaled antibiotic for between one and four weeks. DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible trials, assessed the risk of bias in each trial and extracted data. They assessed the quality of the evidence using the GRADE criteria. Authors of the included trials were contacted for more information. MAIN RESULTS: Four trials with 167 participants are included in the review. Two trials (77 participants) compared inhaled antibiotics alone to intravenous antibiotics alone and two trials (90 participants) compared a combination of inhaled and intravenous antibiotics to intravenous antibiotics alone. Trials were heterogenous in design and two were only available in abstract form. Risk of bias was difficult to assess in most trials, but for all trials we judged there to be a high risk from lack of blinding and an unclear risk with regards to randomisation. Results were not fully reported and only limited data were available for analysis.Inhaled antibiotics alone versus intravenous antibiotics aloneOnly one trial (n = 18) reported a perceived improvement in lifestyle (quality of life) in both groups (very low-quality of evidence). Neither trial reported on time off work or school. Both trials measured lung function, but there was no difference reported between treatment groups (very low-quality evidence). With regards to our secondary outcomes, one trial (n = 18) reported no difference in the need for additional antibiotics and the second trial (n = 59) reported on the time to next exacerbation. In neither case was a difference between treatments identified (both very low-quality evidence). The single trial (n = 18) measuring adverse events and sputum microbiology did not observe any in either treatment group for either outcome (very low-quality evidence).Inhaled antibiotics plus intravenous antibiotics versus intravenous antibiotics aloneNeither trial reported on quality of life or time off work or school. Both trials measured lung function, but found no difference between groups in forced expiratory volume in one second (one trial, n = 28, very low-quality evidence) or vital capacity (one trial, n = 62). Neither trial reported on the need for additional antibiotics or the time to the next exacerbation; however, one trial (n = 28) reported on hospital admissions and found no difference between groups. Both trials reported no difference between groups in adverse events (very low-quality evidence) and one trial (n = 62) reported no difference in the emergence of antibiotic-resistant organisms (very low-quality evidence). AUTHORS' CONCLUSIONS: There is little useful high-level evidence to judge the effectiveness of inhaled antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis. The included trials were not sufficiently powered to achieve their goals. Hence, we are unable to demonstrate whether one treatment was superior to the other or not. Further research is needed to establish whether inhaled tobramycin may be used as an alternative to intravenous tobramycin for some pulmonary exacerbations.

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).

Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis.

BACKGROUND: Cystic fibrosis is a genetic disorder in which abnormal mucus in the lungs is associated with susceptibility to persistent infection. Pulmonary exacerbations are when symptoms of infection become more severe. Antibiotics are an essential part of treatment for exacerbations and inhaled antibiotics may be used alone or in conjunction with oral antibiotics for milder exacerbations or with intravenous antibiotics for more severe infections. Inhaled antibiotics do not cause the same adverse effects as intravenous antibiotics and may prove an alternative in people with poor access to their veins. OBJECTIVES: To determine if treatment of pulmonary exacerbations with inhaled antibiotics in people with cystic fibrosis improves their quality of life, reduces time off school or work and improves their long-term survival. SEARCH METHODS: We searched ClinicalTrials.gov and the Australia and New Zealand Clinical Trials Registry for relevant trials. Date of last search: 15 March 2012We also searched the Cochrane Cystic Fibrosis Group's Cystic Fibrosis Trials Register. Date of the last search: 01 June 2012. SELECTION CRITERIA: Randomised controlled trials in people with cystic fibrosis with a pulmonary exacerbation in whom treatment with inhaled antibiotics was compared to placebo, standard treatment or another inhaled antibiotic for between one and four weeks. DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible trials, assessed the risk of bias in each trial and extracted data. Authors of the included trials were contacted for more information. MAIN RESULTS: Six trials with 208 participants were included in the review. Trials were heterogenous in design and interventions (however, all included trials compared inhaled versus intravenous antibiotic regimens). Risk of bias was difficult to assess in most trials. Results were not fully reported and only limited data were available for analysis. Four trials reported some results on forced expiratory volume at one second and found no significant differences between the inhaled antibiotic and the comparison intervention. In two of these trials using 300 mg of inhaled tobramycin, the change in forced expiratory volume at one second was similar to intravenous tobramycin; and in one trial the time until the next exacerbation was not different. No important adverse effects were reported. AUTHORS' CONCLUSIONS: There is little useful high-level evidence to judge the effectiveness of inhaled antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis. The included trials were not sufficiently powered to achieve their goals. Hence, we are unable to demonstrate whether one treatment was superior to the other or not. Further research is needed to establish whether inhaled tobramycin may be used as an alternative to intravenous tobramycin for some pulmonary exacerbations.

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.

In vitro elution of amikacin and ticarcillin from a resorbable, self-setting, fiber reinforced calcium phosphate cement.

OBJECTIVE: To determine in vitro elution characteristics of amikacin and ticarcillin from fiber reinforced calcium phosphate beads (FRCP). SAMPLE POPULATION: Experimental. METHODS: FRCP beads with water (A), amikacin (B), ticarcillin/clavulanate (C), or both amikacin and ticarcillin/clavulanate (D) were bathed in mL phosphate-buffered saline (PBS) at 37°C, 5% CO(2) and 95% room air. PBS was sampled (eluent) and beads were placed in fresh PBS at time points 1 and 8 hours and 1, 2, 3, 4, 5, 6, 7, 10, 12, 14, 18, 21, 25, 28, 35, 42, 49, and 56 days. Antibiotic concentration and antimicrobial activity of eluent against Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae were determined. RESULTS: Both antibiotics eluted in a bimodal pattern. Beads with a single antibiotic eluted 20.8 ± 2.5% of amikacin and 29.5 ± 0.8% of ticarcillin over 56 days. Coelution of the antibiotics resulted in a lower proportion (AUC(0-∞) ) of antibiotics eluted for both amikacin (9.5 ± 0.2%) and ticarcillin (21.7 ± 0.09%). Bioassay of antimicrobial activity of the eluent (t = 1, 8, and 24 hours) established reduced antimicrobial activity of amikacin from combination beads (D). CONCLUSIONS: FRCP beads with amikacin or ticarcillin/clavulanate, but not the combination, are suitable carriers for wound implantation. CLINICAL RELEVANCE: Duration before complete resorption of FRCP beads in vivo should be determined before clinical use as a resorbable depot. The results of this study underscore the importance of testing drug combinations, despite success of the combination systemically, before their use in local applications.

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.

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.

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.

Pneumonia after cardiac surgery is predictable by tracheal aspirates but cannot be prevented by prolonged antibiotic prophylaxis.

BACKGROUND: The purpose of this study was to assess the value of tracheal aspirate as a predictor of pneumonia after coronary artery bypass grafting and to evaluate the efficacy of prolonged perioperative antibiotic prophylaxis. METHODS: Tracheal aspirates of 500 patients undergoing coronary artery bypass grafting were taken immediately after intubation and analyzed for microorganisms by Gram stain and semiquantitative microbiologic cultures. All patients received 2 g ceftriaxone as a single-dose perioperative antibiotic prophylaxis before operation. Results of Gram stains were available before the patients were transferred to the intensive care unit. After the results were known, both groups of patients (positive Gram stain, group 1; negative Gram stain, group 2) were randomly assigned to either conventional antibiotic prophylaxis (A), consisting of ceftriaxone 2 g on postoperative day 1, or prolonged antibiotic prophylaxis (B), with ticarcillin + clavulanic acid 3 x 5.2 g during 72 hours. RESULTS: From 500 patients, 91 had a positive Gram stain whereas 409 had a negative one. The incidence of pneumonia was significantly higher in patients with preoperative positive tracheal aspirates (15.3%) than in patients with a negative one (3.6%; p < 0.01). However, prolonged prophylaxis did not reduce the rate of postoperative pneumonia, which was as high as 13% in untreated positive patients versus 17% in treated positive patients, and 2% in untreated negative patients versus 4% in treated patients. In patients who had pneumonia, there was a high correlation between the microorganisms found in preoperative aspirates and those observed when aspirates were repeated (100% correlation in patients with conventional antibiotic prophylaxis and 87% in those with prolonged prophylaxis). CONCLUSIONS: Early postoperative pneumonia (<7 days) is most likely caused by microorganisms that colonize the respiratory tract before operation. The risk of pulmonary infection after coronary artery bypass grafting can be predicted from the preoperative tracheal aspirates. Prolonged perioperative antibiotic prophylaxis has no efficacy in reducing the incidence of pulmonary infections.

[Antibiotic prophylaxis of postoperative complications in surgical treatment of pulmonary, tracheal and mediastinal tumors]. / Antibiotikoprofilaktika posleoperatsionnykh oslozhnenii pri khirurgicheskom lechenii opukholei legkikh, trakhei i sredosteniia.

A protocol of antibiotic protection, developed and used at Russian Research Center of Roentgenoradiology, is presented. This protocol of perioperative treatment is intended for control of a spectrum of bacterial infections retrospectively detected in patients with lung, tracheal, and mediastinal cancer. The efficiency of perioperative antibiotic prevention is demonstrated as exemplified by 105 patients of different age with various concomitant diseases.

Single-versus multiple-dose antibiotics prophylaxis for cardiac surgery.

BACKGROUND: This study was carried out to determine if single-dose antimicrobial prophylaxis is sufficient for cardiac surgery. METHODS: The study was a prospective non-randomized trial of 353 consecutive patients undergoing cardiac surgery. Group A (n = 151) received 48 h of prophylaxis and Group B (n = 202) received a single dose. Cephazolin was used in all patients except those at high risk from methicillin-resistant Staphylococcus aureus (MRSA) who received teicoplanin and timentin. RESULTS: There was an overall in-hospital infection rate of 2.8%. There was no significant difference in rate or type of infection between the two groups. CONCLUSIONS: An in-hospital infection rate of 2.8% compares favourably with other reported series. Single-dose antimicrobial prophylaxis is as effective as a 48-h regimen. Targeting high-risk groups is effective.

[A trial of using timentin (ticarcillin/clavulanate) in treating abdominal surgical infection]. / Opyt primeneniia timentina (tikartsillin/klavulanata) v lechenii abdominal'noi khirurgicheskoi infektsii.

Efficacy of timentin was studied in the treatment of 19 patients with peritonitis of various etiology and clinical and laboratory signs of systemic inflammatory reaction characteristic of abdominal sepsis. The clinical and bacteriological effects were recorded in 84.2 and 87.5 per cent of the cases respectively. The drug was administered intravenously dropwise for 30 minutes in a dose of 3.1 g every 4 hours. The treatment course was 4-11 days. The treatment failed in 3 patients. One of them had general peritonitis of gynecological etiology. In the other no significant regression of abdominal sepsis was observed, Pseudomonas aeruginosa strains were isolated from the abdominal cavity, the antibiotic was changed, still incurable polyorganic insufficiency developed and the patient died. The third patient had perforation of the large intestine due to tumor. No adverse reactions to the use of timentin in any of the cases was observed.

Effect of topical antibiotic therapy on recovery after tonsillectomy in adults.

OBJECTIVE: Systemic antibiotics given during the first week after tonsillectomy appear to be effective in reducing postoperative morbidity. We assessed the effectiveness of perioperative topical antibiotic rinses in reducing posttonsillectomy morbidity. METHODS: A randomized, double-blinded, placebo-controlled pilot study of 36 patients undergoing tonsillectomy was used to evaluate the effects of a standard 7-day systemic regimen of perioperative intravenous ampicillin/oral amoxicillin and 2 single-day topical antibiotic regimens: (1) clindamycin (Cleocin) and (2) amoxicillin/clavulanate (Augmentin) and ticarcillin/clavulanate (Timentin). RESULTS: Mean aerobic and anaerobic oral bacterial counts were decreased in both topical treatment groups compared with the placebo group on the first postoperative day, achieving statistical significance with Augmentin/Timentin (aerobic and anaerobic bacterial counts) and Cleocin (aerobic counts). Significantly less postoperative pain and mouth odor were reported for both Cleocin (P = 0.014 and P = 0.005, respectively) and Augmentin/Timentin (P = 0.026 and P = 0.05, respectively) topical treatment groups when compared with the placebo group. CONCLUSIONS: Preliminary results indicate a reduction in oral bacterial counts and postoperative morbidity in adult patients receiving topical antibiotics compared with patients receiving placebo; further investigation is warranted.

Alcaligenes xylosoxidans keratitis post penetrating keratoplasty in a rigid gas permeable lens wearer.

PURPOSE: We report a case of Alcaligenes xylosoxidans keratitis following penetrating keratoplasty in a rigid gas permeable (RGP) lens wearer. METHODS: A 61 year old RGP lens wearer with a history of nonresponsive keratitis of the right eye which involved the graft margin was referred to us for treatment. Corneal cultures revealed growth of a gram-negative rod on the fifth day and the organism was subsequently identified as Alcaligenes xylosoxidans, which was resistant to most antibiotics and sensitive only to Bactrim, Timentin, and imipenem. RESULTS: Clinical improvement was observed within 24 hours after treatment with the use of topical i.v. Bactrim and topical i.v. Timentin 2% alternating every 30 minutes. Complete resolution of the infection with mild scarring was observed 6 weeks after treatment. CONCLUSIONS: Alcaligenes xylosoxidans is a potential cause of bacterial keratitis which should be considered in cases of nonresponsive gram-negative keratitis. The addition of topical Bactrim or Timentin may need to be considered in such cases.

Duration of antimicrobial prophylaxis in vascular surgery.

BACKGROUND: This randomized clinical trial compares the incidence of wound infection after vascular surgery in patients who received prophylaxis using the same antibiotic as either a single-dose or a multiple-dose regimen (until the lines/drain tubes were removed, but not for more than 5 days). METHODS: Each of the 302 patients who entered the study received ticarcillin 3.0 g/clavulanate 0.1 g (Timentin) intravenously immediately after the induction of anesthesia. Patients randomized to the multiple-dose group received an average of 14.3 doses (range 9 to 20). RESULTS: The incidence of wound infections was 18% (28 of 153) for patients in the single-dose group and 10% (15 of 149) for patients in the multiple-dose group (P = 0.04; relative risk estimate = 2.00, 95% confidence interval = -1.02 to 3.92). CONCLUSIONS: A multiple-dose antibiotic regimen, rather than single-dose therapy, provides optimal prophylaxis against wound infection for patients undergoing vascular surgery.

Randomized comparison between antibiotics alone and antibiotics plus granulocyte-macrophage colony-stimulating factor (Escherichia coli-derived in cancer patients with fever and neutropenia.

PURPOSE: A prospective, randomized study was conducted to determine if recombinant human granulocyte-macrophage colony-stimulating factor (rh-GMCSF) (Escherichia coli-derived) could improve response rates to antibiotic therapy and shorten the duration of neutropenia in cancer patients. PATIENTS AND METHODS: A total of 107 febrile neutropenic cancer patients were randomly assigned to empiric therapy with ticarcillin-clavulanate (4 g ticarcillin + 0.1 g clavulanate i.v. every 4 hours) plus netilmicin (2 mg/kg i.v. every 8 hours) with or without rh-GMCSF (3 micrograms/kg per day i.v.). Clinical improvement, duration of neutropenia, and toxicity were monitored. RESULTS: Addition of rh-GMCSF to the antibiotics significantly improved the response rate (96% versus 82%, P = 0.03), but not the survival rate (93% versus 93%), in the evaluable patients. This difference in response rate was not significant when considering all patients in an intent-to-treat analysis. The number of patients who recovered from severe neutropenia ( < 100 cells/microliter) during the period of observation in the study was significantly greater among patients receiving the colony-stimulating factor, although the median duration of neutropenia was not affected. Superinfections and subsequent infections were not significantly different among the two treatment regimens. Side effects were more common among patients treated with the colony-stimulating factor. CONCLUSIONS: Our data do not support the routine administration of rh-GMCSF with antibiotics for patients with fever and neutropenia. Further studies should be conducted to identify those patients most likely to benefit from rh-GMCSF therapy, such as patients with persistent profound neutropenia and refractory infections.

Ototoxicity of topical ticarcillin and clavulanic acid in the chinchilla.

BACKGROUND: Currently available topical otic preparations contain a variety of antibiotics and other ingredients that are potentially damaging to the middle and inner ear. There is therefore a need to identify agents that are safe as well as effective for topical otologic use. In pursuit of that goal, we used an animal model to evaluate the ototoxic potential of the broad-spectrum, penicillin derivative ticarcillin--both alone and combined with clavulanic acid (a beta-lactamase inhibitor). METHODS: Twenty chinchillas served as subjects. Ten of the animals were given a single middle ear application of ticarcillin; the remaining 10 animals received ticarcillin disodium plus clavulanate potassium (Timentin). Five animals from each of the two groups were killed after 1 week to assess short-term effects and the other five animals in each group were kept for 4 weeks before their temporal bones were removed for histologic study. RESULTS: Significant toxic effects, involving both the middle and inner ear, were observed in all experimental groups. Alterations of the middle ear at 1 week included inflammation, hemorrhage, and effusions. Middle ear cholesteatomas were observed at 4 weeks. Inner ear changes seen at 1 and 4 weeks included hair cell loss, supporting cell degeneration, and strial damage. CONCLUSION: The study results indicate that ticarcillin should not be considered for further evaluation as a possible antibiotic for use in ototopical preparations.

Efficacy of topical amoxicillin plus clavulanate/ticarcillin plus clavulanate and clindamycin in contaminated head and neck surgery: effect of antibiotic spectra and duration of therapy.

This prospective, randomized trial was designed to determine the efficacy and mechanism of action of topical mouthwash versus parenterally administered perioperative prophylactic antibiotics in contaminated head and neck surgery. Patients were randomly assigned to 1 of 4 treatment groups: 1 day of parenteral clindamycin (standard prophylaxis), 1 day of topical clindamycin, 5 days of topical clindamycin, or 1 day of topical amoxicillin plus clavulanate/ticarcillin plus clavulanate. Patients who received the latter regimen had fewer bacteria postoperatively compared with the other 3 treatment groups. The number of gram-negative aerobic bacilli on postoperative oral cavity cultures was increased in all 3 clindamycin groups but not in the amoxicillin plus clavulanate/ticarcillin plus clavulanate group. Parenteral clindamycin appears to exert its effect by being in the neck tissues at the time of surgery; however, all 3 topical regimens were more effective at reducing the number of bacteria in the neck viscera. Topical antibiotic prophylaxis was simple, safe, effective, and well tolerated.