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There are very limited data on ticarcillin-clavulanate elimination by haemofiltration. We measured in vitro ticarcillin-clavulanate adsorption to polyacrylonitrile (PAN) filters and the sieving coefficient using a well-described bench model of haemofiltration. The dose of ticarcillin-clavulanate was 60/2 mg or 180/3 mg, and 0 or 12 g albumin was added to the 1 L of circulating blood-crystalloid mixture to produce four different experimental conditions. The experiment was repeated four times under each condition. Median (interquartile range [IQR] ) ticarcillin adsorption varied from 28 (27-30) mg to 85 (78-90) mg. Adsorption was increased when the dose of ticarcillin was higher (P

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.

Background: Hospital acquired infections (HAIs) are those which are acquired in hospital either due to any intervention or directly through various routes of entry into the body. Nosocomial infection not only adds to functional disability to patients but also increases associated cost of treatment. Major categories of HAIs include pneumonia, urinary tract infections (UTIs), blood stream infections (BSIs), and surgical site infections (SSIs). Methods: The study was conducted to know the incidence of blood stream infections. The patients who developed infections after 48 hours of admission in the ward were included in the study. Blood cultures were performed. A total of 125 seriously ill patients admitted in medicine ward were studied prospectively. Results: Out of a total of 125 patients, 10 (8%) patients developed BSIs. Gram negative isolates Acinetobacter baumannii and Pseudomonas aeruginosa were the most commonly isolated organisms from cases of BSIs. Most of the isolated organisms were susceptible to ticarcillin clavulanic acid. Conclusions: HAI incidence was high in this study. Prevention programs in future should focus on patients with longer length of stay, invasive devices, and injudicious use of antibiotics to contain the incidence of HAIs.

Ticarcillin–clavulanate covers a broad spectrum of pathogens that are common in premature infants. In infants 90% of simulated infants. For highly resistant organisms (minimum inhibitory concentration 32 μg/mL), increased dosing frequency or extended infusion are necessary.

Inducible expression of L1 and L2 β-lactamases is the principal mechanism responsible for β-lactam resistance in Stenotrophomonas maltophilia. Ticarcillin-clavulanate (TIM) is one of the few effective β-lactams for S. maltophilia treatment. Clavulanate (CA) is a β-lactamase inhibitor that specifically targets class A, C, and D β-lactamases. In view of the presence of class B L1 β-lactamase, it is of interest to elucidate why TIM is valid for S. maltophilia treatment. The L1-L2 allelic variation and TIM susceptibilities of 22 clinical isolates were established. Based on L1 and L2 protein sequences and TIM susceptibility, three L1-based phylogenetic clusters (L1-A, L1-B, and L1-C) and three L2-based phylogenetic clusters (L2-A, L2-B1, and L2-B2) were classified. The contribution of each L1- and L2-based phylogenetic cluster to ticarcillin (TIC) and TIM susceptibility was investigated. All the L1s and L2s tested contributed to TIC resistance. The L1s tested were inert to CA; nevertheless, the sensitivities of L2s to CA were widely different. In addition, the genetic organizations upstream of the L1 gene varied greatly in these isolates. At least three different L1 promoter structures (K279a type, D457 type, and none) were found among the 22 isolates assayed. The differences in the L1 promoter structure had a great impact on TIC-induced L1 β-lactamase activities. Collectively, the L1 promoter activity in response to TIC challenge and L2 susceptibility to CA are critical factors determining TIM susceptibility in S. maltophilia.

Pseudomonas aeruginosa is an important opportunistic pathogen in human infections. P. aeruginosa is naturally resistant to many antibiotics and mutations can result in resistance development during treatment as well. Piperacillin/tazobactam and Ticarcillin/clavulanate are β-lactam/β-lactamase inhibitor combination with a wide spectrum of antibacterial activity. In this study was aimed to determine the susceptibility of P. aeruginosa isolates to Piperacillin/tazobactam and Ticarcillin/clavulanate antibiotics by Epsilometer test in the patients in intensive care units of Giresun State Hospital and to compare PIP/TZP results by Disk Diffusion method. Sensitivities of PIP/TZP were determined via Kirby Bauer disk diffusion method and MIC values of the isolates against PIP/TZP and TIC/CLA were determined by E-test. By using E-test method and in accordance with the CLSI standards, 43 (64%) isolates were found to be susceptible and 24 (36%) isolates were found to be resistant to TIC/CLA. For the PIP/TZP, 49 of the 67 isolates were susceptible, three were intermediate and 15 were resistant by using disk diffusion method. On the other hand, according to the E-test results, 63 isolates were susceptible and four isolates were resistant. When compared to eleven isolate E-test methods, the disk diffusion method was incorrectly determined to be resistant. The results of our study suggest that it would be more appropriate to use E-test method to confirm the results of the isolates which were found to be resistant against PIP/TZP by disk diffusion method.

A series of cases of piperacillin-tazobactam (P/T)-associated neutropenia has been observed recently in children in our center. Because neutropenia was seldom observed in children treated with ticarcillin-clavulanic acid (T/C), we conducted a study to determine if there is an increased risk of neutropenia in children exposed to P/T in comparison with T/C.Medical records of subjects aged18 years who received at least 1 dose of P/T or T/C between 1 January 2008 and 30 June 2011 were reviewed.Two hundred ninety-nine episodes of treatment (65 P/T, 234 T/C) met inclusion criteria. Among those episodes, 213 had data allowing complete white blood cell count analysis and were included in the final analysis. Thirteen cases of neutropenia were observed during the study period. The average time to onset was 17.6 days and all patients were aged13 years. Seven cases (10.8%) occurred in the P/T group and 6 (2.6%) in the T/C group (unadjusted odds ratio, 4.59; 95% confidence interval, 1.48-14.17). Although a statistically significant correlation was observed between age, treatment duration, and total dose and the development of neutropenia (r = -0.121, P = .037; r = 0.267, P.001; r = 0.260, P.001, respectively), this was not the case for sex, indications, neutrophil count at initiation, and concomitant drug treatments.Although our results need to be confirmed, they suggest that children receiving long courses of therapy (2 weeks) with P/T may be at increased risk of neutropenia, compared with T/C.

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.

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).

Objectives To investigate in vitro susceptibilities of canine and feline Escherichia coli and canine Pseudomonas spp. isolates to ticarcillin and ticarcillin–clavulanic acid (T/C). Design In vitro susceptibility testing of bacterial isolates collected from infections. Methods We tested 148 (83 canine and 65 feline) E. coli and 61 canine Pseudomonas spp. isolates for susceptibility to T/C using both disc diffusion and Epsilometer tests (E-tests). Additionally, susceptibilities of 96 E. coli and 23 canine Pseudomonas spp. isolates were tested via disc diffusion to ticarcillin alone. Results Of the E. coli isolates obtained from canine and feline urine, 92% by disc diffusion and 91% by E-tests were susceptible to T/C. Of the canine Pseudomonas isolates, 90% by disc diffusion and 82% by E-tests were susceptible to T/C. Of the Pseudomonas spp. isolates from the canine ear canal or tympanic bullae, 12% of isolates tested via disc diffusion and 23% via E-tests were found to be resistant to T/C. The 50% minimum inhibitory concentration of T/C for all feline E. coli isolates was significantly lower than that for all canine E. coli isolates (P = 0.0031). The addition of clavulanic acid significantly increased the efficacy of ticarcillin against E. coli (P< 0.0001), but had negligible effect against canine Pseudomonas spp. isolates. Conclusion Ticarcillin-clavulanic acid has reasonable in vitro efficacy against canine and feline E. coli, and canine Pseudomonas spp. isolates. However, decisions to use this drug therapeutically must be made on prudent considerations to minimise selection for bacterial resistance.

Summary Reasons for performing study A commonly used commercial extender (i.e. INRA 96) contains antimicrobials that may have limited effectiveness. Therefore, addition of ticarcillin-clavulanic acid to this extender is a widespread procedure in the equine breeding industry in the United States. However, such practice has not been critically evaluated. Objectives To evaluate the addition of ticarcillin-clavulanic acid to INRA 96 and different extender and antimicrobial storage conditions on sperm function and antimicrobial effectiveness. Methods Gel-free semen (42 ejaculates from 14 mature Quarter Horse stallions) was extended with INRA 96 and stored for 24 h in an Equitainer II. The effects of added ticarcillin-clavulanic acid and different extender storage procedures on sperm motion characteristics (by computer-assisted analysis), sperm membrane integrity (by fluorescence-based measurement) and suppression of bacterial growth (by aerobic and anaerobic culture methods) were evaluated using analysis-of-variance and Chi-square statistical methods. The P value for significance was set at

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 P. aeruginosa isolates with MICs >32 μg/mL. Additional studies are warranted to determine the clinical effectiveness of this dosing regimen.

Aim: To assess adherence to local ticarcillin/clavulanate prescribing guidelines; to examine the appropriateness of non-compliant prescribing; and to identify patterns of prescribing that could be improved. Method: A convenience sample of patients prescribed ticarcillin/clavulanate was prospectively identified by ward pharmacists over a 9-week period. Their medication charts were retrospectively reviewed by the drug use evaluation pharmacist and data collected on patient demographics, diagnosis, previous penicillin allergy, microbiology, treatment type and compliance with local guidelines. Ticarcillin/clavulanate use that was considered inappropriate was analysed for costs. Results: Of the 100 patients included in the audit, half were prescribed ticarcillin/clavulanate outside of local guidelines. In this non-compliant group, approximately two-thirds (65%) of patients were considered to have been treated appropriately. The majority of these patients were being managed for diabetic foot infections. Prescribing in only 18% of cases was considered to be neither compliant with the guidelines or appropriate. Pharmacoeconomic analysis suggests that efforts to improve prescribing may result in cost savings. Conclusion: There was widespread use of ticarcillin/ clavulanate outside of the local guidelines. In many cases, non-compliant prescribing was considered appropriate.

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.

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/mm³ (T) and 201cells/mm³ (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.

OBJECTIVE: To present a case of cellulitis/myositis due to Stenotrophomonas maltophilia in the absence of trauma and to discuss a potentially novel treatment option. CASE SUMMARY: A 57-year-old white man, having undergone an allogeneic bone marrow transplant, developed myositis with S. maltophilia of the left soleus muscle; there had been no trauma. Risk factors for infection included neutropenia, prolonged hospitalization and intensive care unit stay, and broad-spectrum antibiotic exposure. The affected area of muscle was resected and the patient successfully treated with trimethoprim/sulfamethoxazole (TMP/SMX), ticarcillin/clavulanate, and aztreonam. DISCUSSION: In severe myositis/cellulitis caused by S. maltophilia, TMP/SMX is considered the drug of choice. However, bacteriostatic agents such as TMP/SMX are less than ideal in neutropenic patients. The combination of ticarcillin/clavulanate plus aztreonam has been shown to improve activity in vitro against this organism compared with TMP/SMX. This is likely due to inhibition of the 2 β-lactamases this organism produces by clavulanate and aztreonam. In our study of clinical isolates of S. maltophilia, this combination reduced the minimum inhibitory concentration at 90% by 128-fold and was synergistic against 10 of 12 isolates tested in time—kill analysis. CONCLUSIONS: S. maltophilia is emerging as an important pathogen in patients with compromised immunity, leading to severe infections that are difficult to treat. Based on in vitro synergy studied, we recommend considering ticarcillin/clavulanate plus aztreonam as a potential treatment option in immunocompromised patients with S. maltophilia infection.

The prevalence of Stenotrophomonas maltophilia resistance to ticarcillin-clavulanate has dramatically increased in our hospital over the past few years. Sixty-six clinical isolates, collected from 61 patients, were tested for antibiotic susceptibility and genotyped by two different enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR) systems. Although two small outbreaks were identified in the medical intensive care unit, the remaining 58 strains generated 48 different PCR patterns. The rapid emergence of resistance in S. maltophilia occured in absence of an epidemic and was probably influenced by increasing-b-lactam use in our hospital.

Study Objective. To evaluate the efficacy and cost of treatment with two β-lactam/β-lactamase-inhibitor combinations. Design. Retrospective, open-label multicenter study. Setting. Fifty-four hospitals across the United States. Patients. Eight hundred ninety patients with skin and soft tissue, intraabdominal, gynecologic, respiratory, urinary tract, or other infections that required parenteral antibiotic therapy. Intervention. Patients were administered either ampicillin-sulbactam 1.5 or 3.0 g every 6 hours or ticarcillin-clavulanate 3.1 g every 6 hours. Measurements and Main Results. The agents did not differ significantly in efficacy for most infections; although, ampicillin-sulbactam was bacteriologically superior to ticarcillin-clavulanate in the treatment of intraabdominal infections (p=;0.0011). Costs of ampicillin-sulbactam, particularly the 1.5-g dose, were lower than those of ticarcillin-clavulanate for skin and soft tissue (p

The activity of amoxycillin/clavulanate (Augmentin) and ticarcillin/ clavulanate (Timentin) was tested against 351 strict anaerobic clinical isolates collected from September 1993 to April 1994 in eight Belgian university hospitals and compared with that of 8 other antibiotics using the NCCLS reference agar dilution procedure. Production of beta-lactamase was detected by the nitrocefin test in 48% of the isolates. At NCCLS-recommended breakpoints, more than 90% of isolates were susceptible to amoxycillin/clavulanate, ticarcillin/clavulanate, piperacillin/tazobactam, imipenem, chloramphenicol and metronidazole but only 77%, 72% and 48% to cefoxitin, clindamycin and penicillin, respectively. In comparison with the results of a similar survey conducted in 1987 no major changes in susceptibility were observed except for the susceptibility to clindamycin that declined from 83% to 72% overall, and from 83% to 66% in the B. fragilis group. Furthermore one isolate of Clostridium clostridioforme was found produce beta-lactamase and few B. fragilis group isolates showed reduced susceptibility to metronidazole.

A total of 303 bacterial strains isolated from bronchoaspirates of Intensive Care Unit (ICU) patients, collected through June and December 1993, were tested for susceptibility to ticarcillin/clavulanic acid, imipenem, amikacin, ceftazidime, ciprofloxacin and piperacillin. The minimal inhibitory concentration (MIC) for each antibiotic was determined according to the NCCLS, by means of serial dilution on microplates. The isolates, 80.8% of which were beta-lactamase producing strains, belonged to Pseudomonas aeruginosa (79 strains), Pseudomonas fluorescens (8 strains), Xanthomonas maltophila (25 strains), Escherichia coli (16 strains), Klebsiella-Enterobacter-Serratia (KES) (62 strains), Proteus spp. (15 strains), Acinetobacter spp. (22 strains), Moraxella spp. (15 strains), Bacteroides catarrhalis (8 strains), Haemophilus spp. (11 strains), Staphylococcus aureus (32 strains), Enterococcus faecalis (10 strains). The highest rate of susceptibility to ticarcillin/clavulanic acid (100%) was detected among E. faecalis (MIC 2-16 micrograms/ml), B. catarrhalis (MIC 1-4 micrograms/ml) and Haemophilus spp. (MIC 1-4 micrograms/ml). Among the non-fermenting microorganisms ticarcillin/-clavulanic acid showed good activity toward P. aeruginosa and P. fluorescens (86% and 75% respectively). It was also very active against X. maltophilia with a susceptibility of 96%. Susceptibility to the other antibiotics tested was within the range of 16% and 28%.

The pharmacokinetic characteristics of ticarcillin and clavulanic acid were determined after the first dose (n = 22) and again under steady-state conditions (n = 16) in a group of infants and children. Study subjects ranged in age from 1 month to 9.3 years; all but 3 study patients were 6 months of age or older. Each patient received 50 mg of ticarcillin and 1.7 mg of clavulanic acid (30:1 ratio) per kg of body weight given intravenously every 4 hours. Elimination half-life, steady-state volume of distribution, and body clearance averaged 1.1 hours, 0.22 L/kg, and 2.7 mL/min/kg, respectively, for ticarcillin, and 0.9 hours, 0.4 L/kg, and 6.2 mL/min/kg, respectively, for clavulanic acid. A total of 71% of the ticarcillin and 50% of the clavulanic acid dose were excreted unchanged in the urine over the 4-hour sampling period. Corresponding renal clearances averaged 2.1 and 3.2 mL/min/kg for ticarcillin and clavulanic acid, respectively. No differences were observed between first dose and steady-state evaluations in the pharmacokinetic behavior of either agent. In contrast, the pharmacokinetic behavior of clavulanic acid was significantly different from that observed for ticarcillin. These pharmacokinetic data combined with known in vitro susceptibilities of important clinical pathogens support a dose of 80 mg of ticarcillin and 2.7 mg/kg clavulanic acid per kg body weight given as a fixed dose combination every 8 hours for the treatment of most systemic infections that occur outside the central nervous system.

The objective of the reported study was to characterize the pharmacokinetics of ticarcillin and clavulanic acid in premature low-birth-weight (less than 2,200 g) neonates with presumed sepsis. Eleven infants received 12 courses of ticarcillin-clavulanic acid at 75 mg/kg of body weight intravenously every 12 h. Blood samples were collected at 0.5, 1.5, 4, and 8 h following the infusion of the initial dose. The concentrations of ticarcillin and clavulanic acid were determined by a microbiologic assay. Median (interpatient coefficients of variation) values for the volume of the central compartment, total steady-state volume, distributional clearance, total clearance, and terminal elimination half-life for ticarcillin were 0.030 liter/kg (21%), 0.26 liter/kg (48%), 0.41 liter/h/kg (47%), 0.047 liter/h/kg (47%), and 4.2 h (45%), respectively. For clavulanic acid the parameters were 0.28 liter/kg (32%), 0.36 liter/kg (34%), 11 liters/h/kg (36%), 0.12 liters/h/kg (72%), and 1.95 h (40%), respectively. Our results suggest that the current dosing recommendations of 75 mg/kg every 12 h risk subtherapeutic clavulanic acid concentrations and that 50 mg/kg every 6 h is a more rational dosing strategy.

Susceptibility tests were performed on 2402 of consecutive isolates of Enterobacteriaceae and 254 strains of Pseudomonas aeruginosa in five separate medical centres. Five beta-lactams were evaluated with and without a beta-lactamase inhibitor. The effect of different inhibitors was species specific and the rank order of decreasing efficacy against all enteric bacilli was: cefoperazone-sulbactam > piperacillin-tazobactam > cefoperazone > ticarcillin-clavulanic acid > piperacillin > co-amoxiclav > ampicillin-sulbactam > ticarcillin > ampicillin > amoxycillin.

The efficacy and safety of a new combination parenteral antibiotic, piperacillin/tazobactam, was compared with that of parenteral ticarcillin/clavulanate in the treatment of adult patients with community-acquired lower respiratory tract infections. A total of 299 patients were enrolled in this multicentre, double-blind, comparative study; 177 received piperacillin/tazobactam and 122 received ticarcillin/clavulanate. Of these, 119 met the evaluability criteria (69, piperacillin/tazobactam and 50, ticarcillin/clavulanate). The study drugs (piperacillin/tazobactam 3 g/375 mg or ticarcillin/clavulanate 3 g/100 mg) were given every 6 h by slow iv infusion for a minimum of 5 days. The favourable clinical response (cured and improved) rates of evaluable patients were 84% and 64% at endpoint (P < 0.01) for piperacillin/tazobactam and ticarcillin/clavulanate, respectively. The favourable bacteriological response at the early follow-up (eradicated and presumed eradicated) were 91% and 67% for piperacillin/tazobactam and ticarcillin/clavulanate, respectively (P < 0.01). At endpoint, 84% and 64%, respectively (P = 0.02) had a favourable response. The most common adverse experiences involved the gastrointestinal tract and occurred in 31.6% of the piperacillin/tazobactam group compared with 20.5% in the ticarcillin/clavulanate group (P = 0.02). These events were mild and generally did not affect therapy. Piperacillin/tazobactam appears to be more effective than ticarcillin/clavulanate in this patient population and is generally well tolerated.

Resume Xanthomonas maltophilia est une bacterie opportuniste susceptible d'entrainer des infections severes en particulier chez les malades hospitalises en reanimation. Les principaux problemes poses par l'isolement de ce germe sont la necessite de distinguer colonisation et infection et sa multiresistance habituelle aux antibiotiques. Une etude sur 31 souches isolees aux CHU de Dijon et de Nice a montre que l'ensemble des souches produisait une metalloenzyme entrainant une resistance constante a l'imipeneme ; 28 souches produisaient egalement une beta-lactamase inductible hydrolysant la ticarcilline, la piperacilline, le cefotaxime, la ceftazidime et l'aztreonam. Parmi les combinaisons beta-lactamines/inhibiteurs de beta-lactamases testees, seule l'association de l'acide clavulanique avec la ticarcilline ou l'aztreonam a montre une synergie. L'activite de la formulation ticarcilline + acide clavulanique a ete confirmee chez 13 malades hospitalises dans le service de reanimation de l'hopital Nord du CHU d'Amiens et traites, en monotherapie dans 10 cas, pour pneumopathie ou septicemie. Une guerison clinique et une eradication bacteriologique ont ete obtenues dans 12 cas sur 13. La formulation ticarcilline + acide clavulanique seule ou en association aux quinolones constitue donc une therapeutique efficace in vitro et in vivo des infections a Xanthomonas maltophilia .

Resume La neutropenie associee a la chimiotherapie represente actuellement une cause majeure de morbidite et de mortalite des traitements antineoplasiques en particulier dans la situation extreme de la greffe de moelle osseuse. Dans cette situation de neutropenie, une antibiotherapie probabiliste doit etre administree qui doit se baser non pas exclusivement sur la frequence des germes rencontres mais plutot sur la gravite potentielle des germes en cause. Le Claventin® a deja ete utilise avec succes chez le neutropenique notamment en association avec des aminosides. Pendant une periode de 16 mois, 115 patients consecutifs receveurs de greffe de moelle ont recu de facon empirique une association de Claventin® + tobramycine avec adjonction a 48 heures de vancomycine en cas de non reponse totale de l'hyperthermie. Cent sept patients sont evaluables et ont presente 108 episodes febriles. Trente-sept episodes (34 %) ont ete documentes (Staphylocoque coag neg : 20 (47 %); Staphylococcus aureus : 2 (5 %); Streptocoque : 10 (24 %); Gram negatif : 3 (8 %). Un succes primaire a ete obtenu pour 84 % des patients avec l'association Claventin®-tobramycine, associee ou non a la vancomycine et/ou l'amphotericine B administrees dans 59 % et 40 % des cas respectivement avant la 48eme heure. Une modification de l'antibiotherapie initiale a ete necessaire chez 14 % des patients. Un patient est decede d'infection (Pseudomonas aeruginosa). Ces resultats confirment la bonne adequation de la strategie Claventin® + tobramycine ± vancomycine et de la posologie choisie de Claventin® (3 g × 4).

A model of localised abscess formation was used to establish mixed infections caused by Escherichia coli and Bacteroides fragilis. The beta-lactamase producing, ticarcillin-resistant strains E. coli E96 and B. fragilis VPI 8708 were used to produce one infection, and in another infection, a beta-lactamase hyperproducing strain E. coli 41548 was combined with a ticarcillin-susceptible strain, B. fragilis B3. Treatment, at doses producing clinically achievable concentrations in mouse serum, began 1 h after inoculation, and continued three times daily for four days. Bacterial numbers in infected tissue were measured at intervals. Against both infections, ticarcillin was ineffective in preventing bacterial growth and abscess formation in all mice. Piperacillin prevented abscess formation in 60% of the mice infected with E. coli E96/B. fragilis VPI 8708, and in 40% of those in the E. coli 41548/B. fragilis B3 group. Therapy with ticarcillin/clavulanic acid or cefoxitin reduced the number of both organisms at the site of infection, and thus prevented abscess formation in 100% treated animals.

Stenotrophomonas maltophilia has emerged as an important opportunistic pathogen, causing infections whose management is often problematic due to its inherent resistance to many antibiotics, making co-trimoxazole the main therapeutic option. However, there are cases in which either due to antimicrobial resistance or allergic reactions and intolerance to co-trimoxazole this antibiotic cannot be administered. We sought to evaluate the available clinical evidence regarding potentially effective alternative antibiotics for the treatment of S. maltophilia infections.The literature search was performed in the PubMed and Scopus databases. The search string used was 'Stenotrophomonas maltophilia OR Xanthomonas maltophilia'.Thirty-one case reports and 5 case series were retrieved including a total of 49 patients with a variety of infections. Twenty of 49 cases (40.8%) were treated with ciprofloxacin as monotherapy or in combination with other antibiotics; 12 of 49 cases (24.5%) were treated with ceftriaxone- or ceftazidime-based regimens; and 6 of 49 cases (12.2%) were treated with ticarcillin- or ticarcillin/clavulanate-based regimens. The cure or improvement rates were 18 cases (90%), 8 (75%) and 4 (66.7%), respectively. The remaining 11 patients received various antimicrobials including aminoglycoside-based regimens, carbapenems, levofloxacin, chloramphenicol, aztreonam, minocycline and other beta-lactams.The limited available data suggest that ciprofloxacin, ceftazidime or ceftriaxone, and ticarcillin/clavulanate, alone or in combination with other antibiotics, may be considered as alternative options beyond co-trimoxazole.

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 (ANC100 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.

Background: In the modern era of increased use of β-lactam antibiotics, resistances to bacteria become a major problem. To overcome this specific resistance mechanism, β-lactam antibiotics are often given with β-lactamase inhibitors like clavulanicacid, salbactam or tazobactam. Aims and Objectives: To comparein vitro activity of betalactam/beta-lactamase inhibitor combinations (Amoxycillin / Clavulanic acid, Ticarcillin / Clavulanic acid and piperacillin/Tazobactam) among gram negative isolates. Material and method: Gram negative bacilli found resistant to penicillin drugs or one or more cephalosporin drugs, were tested for three β-lactam / β-lactamase inhibitor combinations. Antibiotic susceptibility testing was carried out by disc diffusion method as per CLSI guidelines. Result: Total 7800 samples were received, from these 3816 were positive and 3984 were negative for isolates. From positive culture, 1000 were GPC and 2819 were GNB. Susceptibility of the enterobacteriaceae to Augmentin, Piperacillin-Tazobactam and Ticarcillin-Clavulanicacid were 34.82%, 71.64% & 39.8%. Conclusion: Overall piperacillin/ tazobactam was observed to be the best combination agent. Comparative Evaluation of the in Vitro Activity of Three Combinations of Beta-Lactams with BetaLactamase Inhibitors: Amoxicillin/Clavulanic Acid, Piperacillin/Tazobactam and Ticarcillin/ Clavulanic Acid.

The exposure of bacteria to various groups of antimicrobials at different concentrations can produce damage to the bacteria that persists even after removal of the antimicrobial agent. The post antibiotic effect (PAE) of beta-lactams on aerobic gram-negative bacilli is relatively short (

This study tested whether levofloxacin, at a new high dose of 750 mg, was effective for the treatment of complicated skin and skin-structure infections (SSSIs). Patients with complicated SSSIs (n=399) were randomly assigned in a ratio of 1:1 to 2 treatment arms: levofloxacin (750 mg given once per day intravenously [iv], orally, or iv/orally) or ticarcillin-clavulanate (TC; 3.1 g given iv every 4-6 hours) followed, at the investigator's discretion, by amoxicillin-clavulanate (AC; 875 mg given orally every 12 hours). In the clinically evaluable population, therapeutic equivalence was demonstrated between the levofloxacin and TC/AC regimens (success rates of 84.1% and 80.3%, respectively). In the microbiologically evaluable population, the overall rate of eradication was 83.7% in the levofloxacin treatment group and 71.4% in the TC/AC treatment group (95% confidence interval, -24.3 to -0.2). Both levofloxacin and TC/AC were well tolerated. These data demonstrate that levofloxacin (750 mg once per day) is safe and at least as effective as TC/AC for complicated SSSIs.

Background and purpose An increased incidence of post-surgical infectious complications in children admitted with a diagnosis of perforated appendicitis led to development of a disease-specific antibiogram and modification of our post-operative antibiotic regimen. Methods A historical control group comprised of 32 pediatric patients receiving ampicillin, gentamicin, and clindamycin (group AGC) was compared to a cohort of 32 children receiving ticarcillin/clavulanate plus gentamicin (group TG). The surgical procedure, peri-operative management, and inclusion, exclusion and discharge criteria were the same for each group. Outcome measures including length of stay, time to defervesce, incidence of infectious complications, and clinical failures to the antibiotic regimen were compared. Results The groups were similar with respect to gender, age, weight, surgical time, pre-operative leukocytes, and number of intra-operative bacterial isolates cultured per patient. Length of stay was 10.1 days in group TG and 12.5 days for group AGC (p = 0.0197). The number of clinical failures was reduced from 9 (28.1%) to 2 (6.3%) in group TG (p = 0.02). The time to defervesce was decreased by 1.4 days, and the number of infectious complications was reduced to 2.5-fold in group TG patients. Conclusions Ticarcillin/clavulanate plus gentamicin was clinically more effective than ampicillin, gentamicin, and clindamycin combination therapy in the management of perforated appendicitis in our pediatric population.

Um total de 40 cepas do grupo B. fragilis foi isolada de espécimes clínicos em dois centros hospitalares de Fortaleza no período de 1993 a 1997. A espécie mais frequentemente isolada foi Bacteroides fragilis (19 cepas) tendo a maioria dos microrganismos sido isolada de infecção intra-abdominal e ferida cirúrgica infectada. Foi traçado o perfil de sensibilidade à cefoxitina, cefoperazona e associação ticarcilina-ácido clavulânico, utilizando-se o método de referência de diluição em ágar. Todas as espécies testadas apresentaram sensibilidade à ticarcilina-ácido clavulânico (128/2mig/ml). Percentuais de resistência de 15 e 70% foram detectados para cefoxitina (64mig/ml) e cefoperazona (64mig/ml) respectivamente. A espécie B. fragilis apresentou os menores percentuais de resistência quando comparada com as demais espécies do grupo. Estes resultados regionais permitem uma melhor orientação na escolha deste grupo de antibióticos, para profilaxia ou terapêutica, principalmente com relação à cefoxitina que é frequentemente empregada nos centros hospitalares estudados. A total of 40 strains of the B. fragilis group was isolated from clinical specimens in two hospital centers in Fortaleza from 1993 to 1997. The most frequently isolated species was Bacteroides fragilis (19 strains) and most isolates came from intra-abdominal and wound infections. The susceptibility profile was traced for cefoxitin, cefoperazone and ticarcillin-clavulanate by using the agar dilution reference method. All isolates were susceptible to ticarcillin-clavulanate (128/2mug/ml). Resistance rates of 15 and 70% were detected to cefoxitin (64mug/ml) and cefoperazone (64mug/ml), respectively. Such regional results permit a better orientation in choosing this group of antibiotics for prophylaxis and therapy especially in relation to cefoxitin, which is frequently used in the hospital centers studied.

A mouse model of intestinal colonization with vancomycin-resistant enterococci (VRE) was used to study the effect of different beta-lactam antibiotics on establishment of VRE colonization. A clinical VanB VRE isolate, Enterococcus faecium C68 (102 or 104 cfu), was inoculated by gastric gavage in conjunction with subcutaneous administration of antibiotics. The MIC of ceftriaxone and ticarcillin against VRE strain C68 is >10,000 microg/mL, and the MIC of piperacillin is 1250 microg/mL. Ceftriaxone and ticarcillin-clavulanate treatment groups developed persistently high levels of stool VRE compared with both the saline and the piperacillin-tazobactam (Pip-Taz) groups (P

OBJECTIVETo provide an overview of the clinical pharmacokinetics and pharmacodynamics of ticarcillin/clavulanic acid and to reassess traditional dosage recommendations based on contemporary pharmacokinetic and pharmacodynamic principles.DATA SOURCESPublished ticarcillin and clavulanic acid pharmacokinetic data derived from infants and children combined with data obtained from a rigorous, dose-escalation study performed in 12 healthy adults. Pharmacodynamic correlates were derived from published in vitro susceptibility data for the combination drug ticarcillin/clavulanic acid.DATA SYNTHESIS:Limited differences were observed in the pharmacokinetic disposition profiles between ticarcillin and clavulanic acid and relative to subject age. Integration of these data with defined pathogen minimum inhibitory concentrations underscores the appropriateness of an extended dosing interval (e.g., q8h to q12h) for many infections and demonstrates the probable therapeutic interchangeability of the following three intravenous dosing regimens: 3.1 g every 6 hours, 75 mg/kg every 8 hours, and 100 mg/kg every 12 hours of a 30:1 ticarcillin/clavulanic acid combination.CONCLUSIONSIntegration of pharmacokinetic and pharmacodynamic data is an appropriate means to assess/reassess dosing recommendations for antimicrobial agents. Initial ticarcillin/ clavulanic acid dose recommendations did not account for known dynamic interactions for this combination antibiotic. Pharmacokinetic data in infants, children, and adults support a less frequent dosing interval (q8h to q12h) for the treatment of infections arising outside the central nervous system.

OBJECTIVE:To reacquaint clinicians with a reportedly rare adverse event of agranulocytosis occurring after long-term administration of vancomycin and ticarcillin/clavulanate, with a subsequent review of other reported cases in the literature.CASE SUMMARY:A 45-year-old white woman with spina bifida developed agranulocytosis (2.7 × 103/mm3white blood cells with only 3% polymorphonuclear leukocytes and no reported eosinophils or basophils) after long-term administration of vancomycin and ticarcillin/clavulanate for decubitus ulcers and chronic osteomyelitis. Consequently, the cell counts rebounded rapidly on discontinuation of both medications and returned to normal within 1 week.DISCUSSION:The incidence of vancomycin-associated neutropenia is presumably rare, but the increased use of vancomycin may disclose a more frequent occurrence. It is suggested that the mechanism for the reaction is immunologically mediated, yet this remains unclear. Although it is difficult to determine the causative agent in this case, vancomycin was most suspect clinically. Ticarcillin/clavulanate is less likely because our patient has since been readmitted and treated with oxacillin, imipenem/cilastatin, and amoxicillin/clavulanate without affecting the white blood cell count. In that regard, it could be reasoned that an immunologic reaction to ticarcillin would have resulted in a similar outcome with other penicillins.CONCLUSIONS:This case serves as a reminder to clinicians that patients receiving long-term treatment with vancomycin should have their white blood cell count monitored at least weekly.

The aim of this study was to determine antimicrobial susceptibility of recent clinical Stenotrophomonas maltophilia isolates from Korea, and to compare the activity levels of several combinations of antimicrobials. A total of 206 non-duplicate clinical isolates of S. maltophilia was collected in 2010 from 11 university hospitals. Antimicrobial susceptibility testing was performed using the Clinical Laboratory Standards Institute agar dilution method. In vitro activity of antimicrobial combinations was tested using the checkerboard method. The susceptibility rates to trimethoprim-sulfamethoxazole and minocycline were 96% and 99%, respectively. The susceptibility rate to levofloxacin was 64%. All of four antimicrobial combinations showed synergy against many S. maltophilia isolates. A combination of trimethoprim-sulfamethoxazole plus ticarcillin-clavulanate was most synergistic among the combinations. None of the combinations showed antagonistic activity. Therefore, some of the combinations may be more useful than individual drugs in the treatment of S. maltophilia infection. Further clinical studies are warranted to validate our in vitro test results.

Quality control guidelines for standardized antimicrobial susceptibility test methods are critical to the continuing accuracy of the tests. In this report, quality control limits were proposed for 22 organism-antimicrobial combinations with minimum inhibitory concentration (MIC) ranges of three or four log2 dilution steps. Disk diffusion zone diameter ranges were proposed for azithromycin compared with Neisseria gonorrhoeae ATCC 49226 and ticarcillin with and without clavulanic acid tested against Staphylococcus aureus ATCC 25923. The data from five or six participating laboratories produced > or = 94.7% of results within proposed MIC limits, and 94.3%-99.0% of zones were found within suggested zone guidelines. These proposed quality control ranges should be validated by in-use results from clinical laboratories.

The efficacy of an antimicrobial agent in the therapy of infection depends upon the interaction of bacteria, antibiotic and phagocytes. The influence of both ticarcillin/clavulanic acid and amoxycillin/clavulanic acid on the phagocytic and bactericidal activity of human PMNs in vitro was investigated. The results show that clavulanic acid, with its beta-lactamase inhibitory properties, potentiated the efficacy of both ticarcillin and amoxycillin, resulting in a significantly increased susceptibility of a beta-lactamase producing strain of Klebsiella pneumoniae to phagocytic and microbicidal activities of human PMNs. Overall, amoxycillin/clavulanic acid showed greater enhancement of the killing of K. pneumoniae by human PMNs.

The activity of 14 antimicrobial agents against 253 clinical isolates of anaerobic bacteria from pediatric infections was assessed by the agar dilution method. Fifty-eight percent of the isolates were from intraabdominal sites. The drugs tested were ampicillin/sulbactam, ticarcillin/clavulanate, ampicillin, sulbactam, piperacillin, cefoxitin, cefotaxime, cefoperazone/sulbactam, clarithromycin, azithromycin, erythromycin, clindamycin, metronidazole, and chloramphenicol. Ticarcillin/clavulanate was active against all isolates. Clarithromycin was the most active macrolide; combination of this agent with its 14-hydroxy metabolite did not result in synergy. Sixty-two percent of Bacteroides fragilis group isolates, 13% of B. fragilis isolates, and 22% of peptostreptococcal isolates were resistant to clindamycin at a concentration of 4 micrograms/mL. The distribution of these strains in clinical specimens and the patterns of antimicrobial susceptibility documented were different from the findings for isolates from adults in the Los Angeles area.