Treatment Of Soft Tissue Infections Research Articles

Pharmacokinetics of Single- and Multiple-Dose Oral Clarithromycin in Soft Tissues Determined by Microdialysis

The antimicrobial spectrum of clarithromycin renders this antibiotic a frequently used option in the treatment of skin and soft-tissue infections. In most cases, these infections are caused by extracellularly proliferating microorganisms. Thus, clarithromycin concentrations achieved in the interstitial space are considered particularly important for clinical efficacy. In the present study, clarithromycin concentrations in plasma and interstitial-space fluid of subcutaneous adipose tissue and skeletal muscle of six healthy male volunteers were assessed by means of the microdialysis technique after oral single-dose administration of 250 mg and multiple doses of 500 mg of clarithromycin twice a day (b.i.d.). The ratios of the area under the concentration-time curve of free clarithromycin from 0 to 24 h calculated for a single dose of 250 mg (fAUC(0-24)) in interstitial-space fluid to the fAUC(0-24) in plasma were 0.29 +/- 0.17 and 0.42 +/- 0.18 for subcutis and skeletal muscle, respectively. For 500 mg of clarithromycin at the steady state (3 to 5 days of intake twice daily), the fAUC(0-24(b.i.d.)) ratios at the steady state were 0.39 +/- 0.04 and 0.41 +/- 0.19 for subcutis and skeletal muscle, respectively. The half-life was around 2 h after a single dose but increased to approximately 4 h in plasma and tissues after repetitive clarithromycin administration. Based on subsequently performed pharmacokinetic-pharmacodynamic calculations, a dosing regimen of 500 mg b.i.d. may be ineffective in the treatment of soft-tissue infections caused by pathogens with a drug MIC higher than 0.125 mg/liter.

Clindamycin in the treatment of soft tissue infections: a review of 15 019 patients.

A retrospective survey of 15 019 patients treated with clindamycin for a soft tissue infection was carried out to determine whether the incidence of serious side effects was sufficient to preclude the continuing use of this antibiotic. Thirteen patients were found to have had severe diarrhoea and 2 of these required inpatient treatment for pseudomembranous colitis. Certain limitations of the use of clindamycin are suggested but, in view of the recently improved understanding of the nature of pseudomembranous colitis and more effective methods of treatment of this complication, it is concluded that this antibiotic still has a useful role to play in the treatment of acute soft tissue infection.

Pharmacokinetics and pharmacodynamics of cefpirome in subcutaneous adipose tissue of septic patients.

The objective of the present study was to evaluate whether cefpirome, a member of the latest class of broad-spectrum cephalosporins, sufficiently penetrates subcutaneous adipose tissue in septic patients. After the administration of the drug at 2 g, tissue cefpirome concentrations in septic patients (n = 11) and healthy controls (n = 7) were determined over a period of 4 h by means of microdialysis. To assess the antibacterial effect of cefpirome at the target site, the measured pharmacokinetic profiles were simulated in vitro with select strains of Staphylococcus aureus and Pseudomonas aeruginosa. The tissue penetration of cefpirome was significantly impaired in septic patients compared with that in healthy subjects. For subcutaneous adipose tissue, the area under the concentration-versus-time curve values from 0 to 240 min were 13.11 +/- 5.20 g . min/liter in healthy subjects and 6.90 +/- 2.56 g . min/liter in septic patients (P < 0.05). Effective bacterial growth inhibition was observed in all in vitro simulations. This was attributed to the significantly prolonged half-life in tissue (P < 0.05), which kept the tissue cefpirome levels above the MICs for relevant pathogens for extended periods in the septic group. By consideration of a dosing interval of 8 h, the values for the time above MIC (T > MIC) in tissue were greater than 60% for pathogens for which the MIC was </=4 mg/liter in all septic patients. The present data indicate that cefpirome is an appropriate agent for the treatment of soft tissue infections in septic patients. However, due to the high interindividual variability of the pharmacokinetics of cefpirome in tissue, dosing intervals of not more than 8 h should be preferred to ensure that susceptible bacterial strains are killed in each patient.

The effect of hyperbaric oxygen therapy on the bout of treatment for soft tissue infections.

Hyperbaric oxygen (HBO) therapy is often combined with antibiotic therapy for infections such as gas gangrene and osteomyelitis. Although numerous investigations have been undertaken to assess the effect of adjunctive HBO therapy on the treatment of infections, the bout of treatment has not been referred in the previous investigations. The purpose of this retrospective study was to evaluate the efficacy of HBO therapy on the bout of treatment for soft tissue infections. In the period between 1994 and 2001, we treated 23 patients with soft tissue infections. Nine patients were treated with antibiotic chemotherapy alone, and 14 patients were treated with a combination of antibiotic chemotherapy and HBO therapy. The mean bout of treatment was compared between these two groups. The mean bout treated with a combination of antibiotic and HBO was significantly shorter than that with antibiotic alone. Our result indicates that HBO therapy combined with antibiotic therapy is able to shorten the bout of treatment for soft tissue infections. Therefore, we recommend HBO therapy combined with antibiotic therapy for soft tissue infections.

Clinical microbiological case: a firm, right infraclavicular mass in an adult woman with connective tissue disease

Clinical microbiological case: a firm, right infraclavicular mass in an adult woman with connective tissue disease

Significance of antibiotic resistance in treatment of soft tissue infections

Soft tissue infections are common. The clinical spectrum includes infections of skin, subcutaneous tissue, and of deeper structures such as fascia and muscles. The pathogenesis of these infections is quite variable. Introduction of microorganisms through skin breaks or through trauma of other soft tissue is usually at the origin of such infections. Staphylococci, especially S. aureus, as well as streptococci, mainly group A streptococci cause most soft tissue infections. In immunocompromised patients or in particuluar circumstances gram-negative bacteria may also be found to cause such infections. Occasionally, infections are polymicrobial. Given the predominance of gram-positive cocci, betalactam antibiotics with good antistaphylococcal activity are the drugs of choice for empiric treatment. Penicillins or cephalosporins that are stable against penicillinase should be chosen, since many staphylococci produce penicillinase. Over the course of the last 40 years staphylococci first became resistant against penicillin, and later developed resistance against methicillin. Methicillin-resistant S. aureus (MRSA) is now a significant problem worldwide. There continue to be major differences in the prevalence of MRSA between geographic regions. In areas with a high prevalence of methicillin resistance among S. aureus, empiric treatment of life-threatening soft tissue infections should include treatment with a glycopeptide (i.e. vancomycin or teicoplanin). New antibiotics such as oxazolidinones (i.e. linezolid) or quinupristin/dalfopristin are interesting alternatives to the glycopeptides in the treatment of soft tissue infections.

Clinafloxacin versus piperacillin/tazobactam in the treatment of severe skin and soft-tissue infections in adults at a veterans affairs medical center

Background: Severe skin and soft-tissue infections (SSTIs), particularly diabetic foot infections, are a source of considerable morbidity and mortality. Inappropriate antimicrobial therapy may contribute to the increasing emergence of bacterial resistance, as well as to increased health care costs. Thus, there is a continuing search for reasonably safe, well-tolerated, and effective antimicrobial agents that are less susceptible to the development of resistance than older agents. Objective: The Department of Veterans Affairs (VA) Medical Center in Nashville, Tennessee, was 1 site in a multicenter, Phase III, randomized, investigator-blinded clinical trial comparing the safety and efficacy of clinafloxacin with those of piperacillin/tazobactam in the treatment of adult patients with SSTI. Methods: Over an 18-month period, patients aged ≥18 years with physical findings of acute bacterial SSTI requiring hospitalization and intravenous antimicrobial therapy were randomized in a 1:1 ratio to receive either clinafloxacin 200 mg IV every 12 hours or piperacillin/tazobactam 3.375 g IV every 6 hours. After a minimum of 3 days of intravenous therapy, a switch to oral therapy with clinafloxacin 200 mg PO every 12 hours or amoxicillin/clavulanate 500 mg PO every 8 hours could be made in the respective treatment groups. Results: The center enrolled 84 patients (42 in each group), all but 1 of whom were male, reflecting the typical VA medical center population. The mean age was 60 years (range, 36–80 years) in the clinafloxacin group and 65 years (range, 35–87) in the piperacillin/tazobactam group; the latter group was significantly older ( P = 0.0482), which could have affected recovery rates. Sixty-six patients were white and 18 were black. The mean (±SD) duration of treatment was 10.69 ± 5.34 days in the clinafloxacin group and 12.07 ± 5.06 days in the piperacillin/tazobactam group; the mean length of stay was 10.83 ± 10.28 days and 14.95 ± 19.20 days, respectively. Fifty-three (63%) patients were switched to oral therapy (21 in the clinafloxacin group, 32 in the piperacillin/tazobactam group). The most commonly isolated pathogens were Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Enterobacter cloacae. Clinical cure rates and microbiologic eradication rates were similar between the 2 treatments. The piperacillin/tazobactam arm experienced more all-cause adverse events than the clinafloxacin arm, although the difference was not statistically significant. The clinafloxacin arm experienced significantly more adverse events (eg, photosensitivity) that were judged by the investigator to be drug related ( P = 0.034). Conclusions: In this study population of hospitalized adults, clinafloxacin was as effective as piperacillin/tazobactam in the treatment of complicated SSTIs. Appropriate precautions must be taken against exposure to sunlight and ultraviolet light in patients receiving clinafloxacin, and adequate monitoring is necessary. Further investigation is necessary into how the phototoxic effects of the fluoroquinolones can be limited.

Outpatient intravenous antimicrobial treatment of soft tissue infections

Outpatient intravenous antimicrobial treatment of soft tissue infections

Breast radiotherapy and lymphedema.

Breast radiotherapy has a low incidence of long term complications. Lymphedema is the most commonly reported complication and adversely affects the quality of life of the breast carcinoma patient. Although its incidence is decreasing, lymphedema still remains a significant concern for patients and their physicians. With the indications for radiotherapy in breast carcinoma management broadening, current strategies to prevent radiation-related lymphedema should be applied and new strategies should be developed. A review of the literature addressing lymphedema as a complication of radiotherapy in breast carcinoma management was performed. Arm, breast, and truncal edema occur after primary breast carcinoma management. The literature supports the view that radiotherapy contributes to arm and breast edema. Lymphedema occurs most commonly in patients who have both axillary radiotherapy and surgery, is often triggered by a soft tissue infection, and is more common in obese patients. The incidence of arm edema is decreasing due to more conservative surgical treatment of the axilla and possibly due to more conservative management of the breast. Trends in breast edema are less discernible. Single-modality treatment of the axilla is associated with a very low incidence of arm edema. Lymphedema continues to be a problem in the care of the breast carcinoma patient. More conservative surgery combined with careful patient selection for nodal radiotherapy reduces its incidence. Radiotherapy technique, prompt treatment of soft tissue infections, and weight loss in obese patients each can contribute to prevention. The risk of lymphedema is greatly surpassed by the benefits of radiotherapy in the care of the breast carcinoma patient.

Breast radiotherapy and lymphedema

Breast radiotherapy has a low incidence of long term complications. Lymphedema is the most commonly reported complication and adversely affects the quality of life of the breast carcinoma patient. Although its incidence is decreasing, lymphedema still remains a significant concern for patients and their physicians. With the indications for radiotherapy in breast carcinoma management broadening, current strategies to prevent radiation-related lymphedema should be applied and new strategies should be developed.A review of the literature addressing lymphedema as a complication of radiotherapy in breast carcinoma management was performed.Arm, breast, and truncal edema occur after primary breast carcinoma management. The literature supports the view that radiotherapy contributes to arm and breast edema. Lymphedema occurs most commonly in patients who have both axillary radiotherapy and surgery, is often triggered by a soft tissue infection, and is more common in obese patients. The incidence of arm edema is decreasing due to more conservative surgical treatment of the axilla and possibly due to more conservative management of the breast. Trends in breast edema are less discernible. Single-modality treatment of the axilla is associated with a very low incidence of arm edema.Lymphedema continues to be a problem in the care of the breast carcinoma patient. More conservative surgery combined with careful patient selection for nodal radiotherapy reduces its incidence. Radiotherapy technique, prompt treatment of soft tissue infections, and weight loss in obese patients each can contribute to prevention. The risk of lymphedema is greatly surpassed by the benefits of radiotherapy in the care of the breast carcinoma patient.

Treatment of soft tissue infections and attitudes to outpatient therapy

Treatment of soft tissue infections and attitudes to outpatient therapy

Predicting mortality from cancer of the uterine cervix from 1991-2001.

The aim was to provide benchmarks by which to judge the success of behaviour change and the cervical cancer screening programme in England and Wales in reducing mortality from this disease over the next decade. Log-linear models and cervical cancer mortality data by age and marital status from 1959-88 were used to predict future mortality in England and Wales. Recombining "predicted" deaths in marital status groups for 1984-88 gave a closer agreement to total mortality observed in those years than predictions based on past trends from 1959-83 among women of all statuses combined. Mortality for 1989-2003 was then predicted, using the data for 1959-1988. The reaggregated marital status forecasts of mortality provide an upper boundary which future observed mortality should not cross if primary and secondary prevention measures are working effectively. The method allows swift comparison of observation with expectation and therefore the rapid evaluation of the overall performance of preventive strategies.

Soft Tissue Infections in the Emergency Department: The Case for the Use of ‘Simple’ Antibiotics

Cellulitis, infected wounds, abscesses, and other bacterial infections of skin and soft tissue are commonly seen in the practice of emergency medicine. Informal observations in a teaching hospital suggest that newer agents having a broader antibiotic spectrum are frequently used for empiric outpatient treatment of mild to moderate soft tissue infections, so information from a prospective study was analyzed to determine whether this practice is appropriate. Healthy adult volunteers were enrolled in a study of the aerobic bacteriology and response to treatment of skin and soft tissue infections. Patients were randomized to receive a 10-day regimen of cephalexin (500 mg bid or qid) or ofloxacin (300 or 400 mg bid). Clinical response was assessed on two follow-up visits. Of 72 patients enrolled, 45 (63%) had cultures positive for pathogens. Cultures in 31 patients (43%) were positive for Staphylococcus aureus, five (7%) grew gram-negative rods, and five (7%) grew streptococcal species. Clinical response rates exceeded 95% in both the cephalexin- and ofloxacin-treated patients. Pathogens isolated from skin and soft tissue infections treated in the emergency department are not exotic or multiply resistant. The bacteriologic profile and clinical course of uncomplicated soft tissue infections indicate that treatment with a "simple" antibiotic, such as cephalexin, will result in resolution of the infection in nearly all cases. Broader spectrum antibiotics are not required for initial treatment of soft tissue infections in the emergency department.

Ampicillin/Sulbactam Compared with Cefazolin or Cefoxitin for the Treatment of Skin and Skin Structure Infections

The increasing prevalence of β-lactamase production by pathogens associated with cellulitis and soft-tissue infections have made the efficacy of standard treatment regimens suspect and demonstrate the need for a reappraisal of optimal medical management for these infections. In an open randomised, prospective study, the efficacy and toxicity of intravenous ampicillin/sulbactam was compared with cefazolin for the treatment of cellulitis and with cefoxitin for the treatment of soft-tissue infections. Ampicillin/sulbactam was given to 24 patients, cefoxitin to 16 and cefazolin to 12 patients. Analysis of clinical and bacteriological responses showed no significant differences between groups despite the fact that by in vitro testing 82 (98%) of isolates from soft-tissue infections were susceptible to ampicillin/sulbactam but only 68 (81%) were susceptible to cefoxitin (p < 0.001). The addition of sulbactam to ampicillin significantly enhanced its in vitro activity against β-lactamase-producing Staphylococcus aureus and anaerobic bacteria. All adverse reactions were subclinical, demonstrable only by mild laboratory abnormalities. Overall, ampicillin/sulbactam appears to be of comparable clinical efficacy in the treatment of polymicrobial soft-tissue infections with cefoxitin, or in the treatment of cellulitis with cefazolin. Additionally, when Enterococcus faecalis and S. aureus are recovered from a single culture, ampicillin/sulbactam, as opposed to cefoxitin monotherapy, would remain effective. Therefore, ampicillin/sulbactam will often be a less expensive therapeutic alternative.

Bacteriology and treatment of soft tissue infections

Bacteriology and treatment of soft tissue infections

Overview of bacterial infections of the skin and soft tissue and clinical experience with ticarcillin plus clavulanate potassium in their treatment

The etiology, diagnosis, and treatment of skin and soft tissue infections are discussed, and the results of clinical experience with ticarcillin plus clavulanate potassium in these diseases at one clinic are reported. In a randomized and controlled clinical trial, the safety and effectiveness of ticarcillin plus clavulanate potassium and cefazolin were compared in the treatment of soft tissue infections in 20 patients. The 12 patients in the group treated with ticarcillin plus clavulanate potassium included 10 men and two women, with a mean age of 61 years; the eight patients in the group treated with cefazolin were five men and three women, with a mean age of 63.8 years. Ticarcillin plus clavulanate potassium was administered for four to 26 days (mean 12.5 days), and cefazolin for four to 20 days (mean 12 days). There were 29 evaluable pathogens in the group receiving ticarcillin plus clavulanate potassium and 22 in the group receiving cefazolin. Of the 29 pathogens in the former group, 22 were eradicated; three reinfections or superinfections occurred but were ultimately eradicated, and four pathogens persisted. Eighteen of the 22 pathogens in the cefazolin-treated group were eliminated and the other four persisted. Clinically, six of the 12 patients in the ticarcillin plus clavulanate potassium-treated group had cures, four showed improvement, and two failed to show a response. In the cefazolin-treated group, five of the eight patients had cures, one showed improvement, and two failed to show a response.

Role of imipenem/cilastatin in the treatment of soft tissue infections

Imipenem/cilastatin was given to 243 evaluable patients with moderately severe to severe soft tissue infections. Cultures prior to therapy yielded Staphylococcus aureus (108 isolates), group D and non-group D enterococci (49), group A streptococci (42), other aerobic gram-positive cocci (72), Pseudomonas aeruginosa (54), Escherichia coil (32), Proteus mirabilis (31), Enterobacter (21), Klebsiella (20), other aerobic gram-negative rods (58), Bacteroides fragilis group (16), and other anaerobes (65). Overall, 95 percent (230 of 243) of the patients treated had clinical cure (137 of 243) or improvement (93 of 243). Of the 506 strains of etiologic bacterial pathogens isolated from these patients and tested against imipenem, 498 (98 percent) were susceptible to the antibiotic. Many were resistant to both older and newer penicillins and cephalosporins. Serial cultures of infection sites revealed that 426 of 498 (86 percent) of pre-therapy bacterial isolates were eradicated by imipenem/cilastatin therapy. Eight of 498 etiologic pathogens (1.6 percent) acquired resistance to imipenem (seven P. aeruginosa and one enterococcus). Such resistance acquisition was associated with clinical failure in two patients. Imipenem/cilastatin appears to be a highly effective, relatively safe therapy of soft tissue infections caused by a wide variety of gram-positive and gram-negative aerobes and anaerobes, both polymicrobial and monomicrobial in nature. Imipenem/cilastatin should be considered particularly when infection by the more antibiotic-resistant of these bacteria is suspected or proved.

Cefonicid: a long-acting, second-generation cephalosporin. Antimicrobial activity, pharmacokinetics, clinical efficacy and adverse effects.

Cefonicid is a new second-generation cephalosporin with a broad antimicrobial spectrum of activity and a prolonged serum elimination half-life. It has good in vitro activity against methicillin-sensitive Staphylococcus aureus, nonenterococcal streptococci, Hemophilus influenzae, Neisseria gonorrhoeae, Neisseria meningitidis and many of the commonly isolated Enterobacteriaceae. Organisms usually resistant to cefonicid include species of Pseudomonas, Serratia, Acinetobacter and Providencia, and Bacteroides fragilis. The drug is 98% protein bound in human serum, which probably contributes to its significant reduction of antimicrobial activity measured in serum. Limited clinical trials have demonstrated it to be effective for surgical prophylaxis and for treating infections of the urinary tract, lower respiratory tract and bone. Failures have been reported in treatment of soft tissue infections and endocarditis caused by S. aureus. A potential cost reduction may be achieved by administering a single daily dose of cefonicid for established infections or a single preoperative dose for effective surgical prophylaxis instead of multiple-dose regimens of other, similar agents.

Comparison of Cefonicid and Cefazolin for Treatment of Soft-Tissue Infections

Cefonicid was compared with cefazolin for the treatment of serious infections of soft tissue. According to a randomized, prospective protocol designed to assign twice as many patients to cefonicid, 38 patients were treated with cefonicid and 19 patients, with cefazolin. Dosages used were 1.0 g once daily intramuscularly or intravenously for cefonicid and 0.5-1.0 g three times a day intramuscularly or intravenously for cefazolin. Clinical diagnoses included cellulitis (39 patients), abscesses (14), infected ulcers (3), and bursitis (1). Bacteriologic diagnoses included Staphylococcus aureus alone (8 patients), group A Streptococcus alone (13), combined S. aureus plus streptococci (8), viridans group streptococci alone (1), and mixed anaerobes (1). Gram-negative rods were isolated from 11 patients, all in mixed cultures with gram-positive species. For two patients, gram-negative organisms were thought to be etiologic. All 57 patients responded satisfactorily to treatment. Treatment with either drug was neither interrupted nor discontinued because of toxicity. Both cefonicid and cefazolin appear to be effective for the treatment of infections of skin and soft tissues. Cefonicid has the advantage of once-daily dosing.

Clindamycin in the treatment of soft tissue infections

Clindamycin in the treatment of soft tissue infections