Adjunctive Use of Intravenous Antibiotic Regional Limb Perfusion in Three Cranes with Distal Limb Infections.
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SUBMITTER: Huckins GL
PROVIDER: S-EPMC8464672 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Septic synovitis is a critical orthopedic condition in horses. Early intervention is key, with antibiotic therapy typically initiated prior to culture and susceptibility reports becoming available. The pharmacokinetics of several antibiotics have been studied in horses for use in intravenous regional limb perfusion (IVRLP) for septic synovitis, including the carbapenem antibiotic, meropenem. For a variety of factors, some veterinary clinicians may select IVRLP meropenem as therapy for these cases. Meropenem is a vital antibiotic in human medicine, making veterinary use divisive. However, verifying the efficacy of meropenem contrasted to other IVRLP antibiotics is essential for appropriate antimicrobial stewardship. To investigate this, equine patient medical records at a single veterinary teaching hospital were examined. Cases treated with meropenem or gentamicin via IVRLP for septic synovitis were retrospectively analyzed for demographics, diagnostics, treatments, outcomes, and adverse effects. Twenty-three meropenem and 37 gentamicin treated horses were analyzed; demographic information was similar between groups. In the meropenem group, nine horses received meropenem only; the remainder received another antibiotic initially then changed to meropenem. Structures infected included joints (meropenem = 13, gentamicin = 17), tendon sheaths (meropenem = 5, gentamicin = 8) and navicular bursae (meropenem = 2, gentamicin = 6). Overall survival to discharge was 86% (52/60), with meropenem 91% (21/23) and gentamicin 84% (31/37), with no statistically significant differences noted between meropenem or gentamicin groups for overall survival to discharge or outcome after discharge. Twenty-four of 26 bacterial isolates obtained from culture were reported as sensitive to imipenem, a carbapenem antibiotic similar to meropenem. Reported susceptibility to other antibiotics such as ceftiofur (n = 22/26), ampicillin (n = 18/26), amikacin (n = 15/26), or gentamicin (n = 12/26) was also frequently present. In the population of this study, antimicrobial activity augmented with IVRLP using either meropenem or gentamicin both appear to be an effective treatment for septic synovial structures, therefore, less critical antimicrobials may be a viable and more judicious treatment option.
| S-EPMC8033006 | biostudies-literature
Project description:Anecdotal accounts of tiludronate administration via intravenous regional limb perfusion (IVRLP) exist despite a lack of information regarding safety for synovial structures in the perfused area. The objective of this study was to determine whether tiludronate concentrations in synovial structures after IVRLP with low dose (0.5 mg, LDT) or high dose (50 mg, HDT) tiludronate remain below a value demonstrated in vitro to be safe for articular cartilage (<19,000 ng/ml), and to determine effects of tiludronate on synovial fluid cytology variables compared to saline perfused control limbs. Using a randomized controlled experimental study design, horses received IVRLP with LDT (n = 6) or HDT (n = 6) in one forelimb and IVRLP with saline in the contralateral limb. Synovial fluid cytology variables and tiludronate concentrations were evaluated in navicular bursae (NB), and distal interphalangeal (DIP) and metacarpophalangeal (MCP) joints one week before and 30-45 min after IVRLP, and in DIP and MCP joints 24 h after IVRLP. Data were analyzed with 2-way rmANOVA (p < 0.05). Highest measured synovial fluid tiludronate concentrations occurred 30-45 min post-perfusion. Mean tiludronate concentrations were lower in LDT limbs (MCP = 39.6 ± 14.3 ng/ml, DIP = 118.1 ± 66.6 ng/ml, NB = 82.1 ± 30.2 ng/ml) than in HDT limbs (MCP = 3,745.1 ± 1,536.6 ng/ml, DIP = 16,274.0 ± 5,460.2 ng/ml, NB = 6,049.3 ± 1,931.7 ng/ml). Tiludronate concentration was >19,000 ng/ml in DIP joints of two HDT limbs. Tiludronate was measurable only in synovial fluid from HDT limbs 24 h post-perfusion. There were no differences in synovial fluid cytology variables between control and treated limbs. Conclusions. In some horses, IVRLP with HDT may result in synovial fluid concentrations of tiludronate that may have adverse effects on articular cartilage, based on in vitro data. IVRLP with LDT is unlikely to promote articular cartilage degradation. Further studies to determine a safe and effective dose for IVRLP with tiludronate are needed.
| S-EPMC4419440 | biostudies-literature
Project description:Intravenous regional limb perfusions (RLP) are widely used in equine medicine to treat distal limb infections, including synovial sepsis. RLPs are generally deemed successful if the peak antibiotic concentration (Cmax) in the sampled synovial structure is at least 8-10 times the minimum inhibitory concentration (MIC) for the bacteria of interest. Despite extensive experimentation and widespread clinical use, the optimal technique for performing a successful perfusion remains unclear. The objective of this meta-analysis was to examine the effect of technique on synovial concentrations of antibiotic and to assess under which conditions Cmax:MIC ≥ 10. A literature search including the terms "horse", "equine", and "regional limb perfusion" between 1990 and 2021 was performed. Cmax (μg/ml) and measures of dispersion were extracted from studies and Cmax:MIC was calculated for sensitive and resistant bacteria. Variables included in the analysis included synovial structure sampled, antibiotic dose, tourniquet location, tourniquet duration, general anesthesia versus standing sedation, perfusate volume, tourniquet type, and the concurrent use of local analgesia. Mixed effects meta-regression was performed, and variables significantly associated with the outcome on univariable analysis were added to a multivariable meta-regression model in a step-wise manner. Sensitivity analyses were performed to assess the robustness of our findings. Thirty-six studies with 123 arms (permutations of dose, route, location and timing) were included. Cmax:MIC ranged from 1 to 348 for sensitive bacteria and 0.25 to 87 for resistant bacteria, with mean (SD) time to peak concentration (Tmax) of 29.0 (8.8) minutes. Meta-analyses generated summary values (θ) of 42.8 x MIC and 10.7 x MIC for susceptible and resistant bacteria, respectively, though because of high heterogeneity among studies (I2 = 98.8), these summary variables were not considered reliable. Meta-regression showed that the only variables for which there were statistically significant differences in outcome were the type of tourniquet and the concurrent use of local analgesia: perfusions performed with a wide rubber tourniquet and perfusions performed with the addition of local analgesia achieved significantly greater concentrations of antibiotic. The majority of arms achieved Cmax:MIC ≥ 10 for sensitive bacteria but not resistant bacteria. Our results suggest that wide rubber tourniquets and concurrent local analgesia should be strongly considered for use in RLP and that adequate therapeutic concentrations (Cmax:MIC ≥ 10) are often achieved across a variety of techniques for susceptible but not resistant pathogens.
| S-EPMC8974993 | biostudies-literature
Project description:ObjectiveWe compare periosteal block and intravenous regional anesthesia (IVRA) as anesthetic techniques for reduction of distal radius fractures when performed by emergency department (ED) clinicians following brief training.MethodsThis was a single-center, nonblinded randomized controlled trial of a convenience sample of patients presenting with distal radius fractures requiring closed reduction. Primary outcome measure was patient reported fracture reduction pain score, rated on a 100-mm visual analog scale. Secondary outcomes included adjunct pain medication use, ED length of stay, remanipulation rates, participant satisfaction, clinician assessed efficacy, and clinician-assessed ease of the procedure.ResultsEighty-one patients were randomized to receive IVRA (n = 41) or periosteal block (N = 40). Reduction pain scores were not normally distributed. Median (25th-75th percentile) pain scores in participants assigned to IVRA and periosteal block were 5 (1-27.5) and 26 (8.5-63) mm, respectively, (p = 0.007). Use of adjunct medications during reduction was higher for the periosteal block group compared with IVRA (57.5% vs. 22.5%, p = 0.003). Remanipulation rates were 17.5% for periosteal block versus 7.5% for IVRA (p = 0.31). There was no difference in length of stay, patient satisfaction, or clinician's assessed ease of the anesthetic technique. There was a difference in clinician's assessment of efficacy between groups, with IVRA described as "extremely effective" by 65% and periosteal block described as "extremely effective" by 25% (p = 0.003).ConclusionsWhen performed by a diverse group of ED clinicians periosteal block provided inferior analgesia to IVRA but may provide an alternative when IVRA cannot be performed.
| S-EPMC9796829 | biostudies-literature
Project description:IntroductionIn-transit melanoma or melanoma presenting as unresectable liver metastases are clinical situations with limited therapeutic options. Regional intra-arterial therapies provide efficacious treatment alternatives for these patients. Through surgical techniques of vascular isolation, regional therapies deliver high-dose chemotherapy to tumor cells while minimizing systemic exposure. However, percutaneous techniques such as isolated limb infusion (ILI) and percutaneous hepatic perfusion (PHP) have been developed, which provide a minimally invasive means of obtaining vascular isolation of target organs.Areas coveredAreas covered in this review include the techniques of ILI and PHP, the chemotherapeutic agents utilized during these regional therapies and the clinical responses seen after ILI and PHP. The pharmacokinetics of regional chemotherapy utilized during ILI and PHP is also reviewed with an additional focus on novel ways to optimize drug delivery to improve response rates and attempts to define the potential systemic manifestations of regional therapeutics.Expert opinionUnresectable hepatic and limb in-transit metastases from melanoma are very difficult to treat. Systemic chemotherapy has largely been ineffective. Both the minimally invasive, percutaneous techniques of ILI and PHP are excellent methods used to deliver extremely high-dose chemotherapy regionally to patients harboring metastatic melanoma confined to an extremity or liver, respectively. Studies, from prospectively maintained databases as well as Phase II and III trials, have shown the great efficacy of these techniques.
| S-EPMC4630979 | biostudies-literature
Project description:BackgroundEfficient pain management is one of the most important components of care in the field of emergency medicine.ObjectivesThis study was conducted to compare intravenous paracetamol and intravenous morphine sulfate for acute pain reduction in patients with limb trauma.Patients and methodsIn a randomized double-blinded clinical trial, all patients (aged 18 years and older) with acute limb trauma and a pain score of greater than 3/10 in the emergency department were recruited; they received either 1 g intravenous paracetamol or 0.1 mg/kg intravenous morphine sulfate over 15 minutes. The primary outcome was the pain score measured on a numerical rating scale at 0, 15 and 30 minutes after commencing drug administration. The requirement for rescue analgesia and the frequency of adverse reactions were also recorded.ResultsSixty patients randomly received either IV paracetamol (n = 30) or IV morphine (n = 30). The mean reduction in numerical rating scale pain intensity scores at 30 minutes was 3.86 (± 1.61) for paracetamol, and 2.16 (± 1.39) for morphine. However, pain relief was significantly higher in the paracetamol group compared to the morphine group (P < 0.001). Four patients in the paracetamol group and 15 patients in the morphine group needed rescue analgesia and the difference was significant (P = 0.05).ConclusionsIntravenous paracetamol appears to provide better analgesia than intravenous morphine in acute limb trauma. Further larger studies are required.
| S-EPMC4869432 | biostudies-literature
Project description:IntroductionIsolated limb perfusion and infusion (ILP/ILI) are therapies for regional metastatic melanoma that allow high doses of anticancer drugs to be delivered directly into the circulation of an affected limb, thereby minimizing systemic drug toxicity. This procedure can lead to high response rates and is recommended in patients with Stage III unresectable metastatic melanoma. However, limited information is available on patterns of use and costs. This study examined patterns of ILP/ILI use and associated costs in patients with melanoma in the United States (US).MethodsRetrospective, observational study, using administrative claims data from the MarketScan(®) databases, was performed in patients with a diagnosis of melanoma (ICD-9-CM: 172.xx, V10.82) who underwent ILP/ILI (CPT-4: 36823) between January 1, 2002 and March 31, 2013. Patient characteristics, use patterns, length of hospital stay, and costs (per 2014 US $) of ILP/ILI were assessed.ResultsOne hundred and thirteen patients met the study criteria and were included in the analysis. Mean age was 61.4 years (standard deviation [SD] 13.8) and 38.9% of patients were male; the mean baseline Charlson Comorbidity Index was 0.19; 34.5% of patients were Medicare beneficiaries. The majority of patients (87.6%) had melanoma of the lower limb, 11.5% of the upper limb, and 0.9% of both limbs; 60.2% had lymph node metastasis and 56.6% had skin metastasis. Four patients (3.5%) underwent multiple ILP/ILI. The mean (± SD) length of hospital stay was 5.6 (± 3.5) days and the mean (± SD) cost was US$36,758 (± 27,124) per ILP/ILI procedure.ConclusionsIsolated limb perfusion and infusion in patients with melanoma were associated with long hospital stays and high costs. These results provide useful source data for the economic evaluation of treatment options for regional metastatic melanoma.FundingThis study was funded by Amgen, Inc.
| S-EPMC4769719 | biostudies-literature
Project description:Following injury to a tendon little is known about potential for pathology to develop in other regional tendons from overloading or altered function. The aim of this study was to investigate the gene expression and histopathological changes that occur 1) within the deep digital flexor tendon (DDFT) after injury to the superficial digital flexor tendon (SDFT) and 2) within the flexor tendons (SDFT and DDFT) after injury to the extensor tendons. Merino wethers [Ovis aries] (n = 18) were divided into three equal groups and underwent either partial transection of the SDFT, complete transection of the extensor tendons or were left as non-operated controls. Tendons were harvested and sampled regionally for gene expression (real time PCR) and histologic analysis eight weeks after surgery. Transection of the SDFT resulted in increased expression of collagen III, versican, biglycan, lumican and MMP1 (P<0.026 for all genes) within the DDFT. There was no effect of transecting the extensor tendons on the expression of any gene tested in either the SDFT or the DDFT. The DDFT had elevated histopathology scores induced by transection of the SDFT, eight weeks previously. There were minimal histological differences in either the SDFT or DDFT after transection of the extensor tendons. Transection of the SDFT results in a mild, subclinical tendinopathy within the DDFT with potential implications on treatment and rehabilitation of SDFT injuries. Injury to the extensor tendons has minimal measured effect on the SDFT or DDFT.
| S-EPMC6478347 | biostudies-literature
Project description:ObjectivesEmergency department (ED) patients with serious skin and soft tissue infections (SSTIs) are often hospitalized to receive intravenous (IV) antibiotics. Appropriate patients may avoid admission following a single-dose, long-acting IV antibiotic.MethodsWe conducted a preintervention versus postintervention design trial at 11 U.S. EDs comparing hospitalization rates under usual care to those using a clinical pathway that included a single IV dalbavancin dose. We enrolled adults with cellulitis, abscess, or wound infection with an infected area of ≥75 cm2 without other indications for hospitalization. Clinical pathway participants discharged from the ED received a 24-hour follow-up telephone call and had a 48- to 72-hour in-person visit. We hypothesized that, compared to usual care, the clinical pathway would result in a significant reduction in the initial hospitalization rate.ResultsOf 156 and 153 participants in usual care and clinical pathway periods, median infection areas were 255.0 (interquartile range [IQR] = 150.0 to 500.0) cm2 and 289.0 (IQR = 161.3 to 555.0) cm2 , respectively. During their initial care, 60 (38.5%) usual care participants were hospitalized and 27 (17.6%) pathway participants were hospitalized (difference = 20.8 percentage points [PP], 95% confidence interval [CI] = 10.4 to 31.2 PP). Over 44 days, 70 (44.9%) usual care and 44 (28.8%) pathway participants were hospitalized (difference = 16.1 PP, 95% CI = 4.9 to 27.4 PP).ConclusionsImplementation of an ED SSTI clinical pathway for patient selection and follow-up that included use of a single-dose, long-acting IV antibiotic was associated with a significant reduction in hospitalization rate for stable patients with moderately severe infections. Registration: NCT02961764.
| S-EPMC8597095 | biostudies-literature
Project description:ObjectiveAntibiotics are the most common class of medication prescribed in pediatrics, with the majority of prescriptions occurring in the outpatient setting. Our objective was to evaluate the accuracy of antibiotic dose, frequency, and formulation prescribed for urinary tract infections (UTIs) in the pediatric ambulatory care setting.MethodsThis was a retrospective review of electronic medical records conducted at 2 suburban pediatric practices in a mid-sized metropolitan region. Encounter-related prescriptions were identified using UTI-associated International Classification of Diseases, 10th Revision codes. Patients aged 2 months through 18 years were included if they had been prescribed an oral antibiotic for the treatment of UTI. Antibiotic dose, frequency, and formulation were considered accurate if consistent with clinical guidelines and tertiary dosing references.ResultsNearly 1 in 4 prescriptions had dosing inaccuracies. The proportion of errors was highest with amoxicillin-clavulanate (75%; 9/12) and amoxicillin (52%; 33/64). The most common reasons for dosing incorrectly were "low dose" or "unnecessarily high dose." Additionally, 55% of the included prescriptions were for oral suspensions, and 1 in 4 of these were dosed incorrectly.ConclusionsInaccuracies in antibiotic prescribing for pediatric UTI are common, including for frequently prescribed agents and oral formulations. To address these missed opportunities for stewardship in the outpatient setting, key educational sessions with providers should include reviewing optimal antibiotic dosing for uropathogens and highlighting common errors when oral suspensions are prescribed.
| S-EPMC8939275 | biostudies-literature