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Biomedical subjects

J S Solomkin

Publications and source records attributed to J S Solomkin.

At least 19 recordsLinked to original sources
PubMed1992

Guidelines for clinical care: anti-infective agents for intra-abdominal infection. A Surgical Infection Society policy statement.

Several antibiotics have been marketed for therapeutic use in intra-abdominal infection. Often, these agents do not provide a sufficient spectrum activity against both facultative and obligate anaerobic gram-negative organisms, or have certain toxic effects that would not otherwise support their use. Guidelines have been developed for selection of antibiotic therapy for intra-abdominal infections and are presented as a statement of the Surgical Infection Society endorsed by the Executive Council. These guidelines are restricted to infections derived from the gastrointestinal tract and deal with those microorganisms commonly seen in such infections. The recommendations are based on in vitro activity against enteric bacteria, experience in animal models, and documented efficacy in clinical trials. Other concerns regarding pharmacokinetics, mechanisms of action, microbial resistance, and safety were also used in the formation of these guidelines. For community-acquired infections of mild to moderate severity, single-agent therapy with cefoxitin, cefotetan, or cefmetazole or ticarcillin-clavulanic acid is recommended. For more severe infections, single-agent therapy with carbapenems (imipenem/cilastatin) or combination therapy with either a third-generation cephalosporin, a monobactam (aztreonam), or an aminoglycoside plus clindamycin or metronidazole is recommended. Regimens with little or no activity against facultative gram-negative rods or anaerobic gram-negative rods are not considered acceptable.

Abdomen↗
PubMed1992

Evaluation of new anti-infective drugs for the treatment of intraabdominal infections. Infectious Diseases Society of America and the Food and Drug Administration.

These guidelines deal with the evaluation of anti-infective drugs for the treatment of intraabdominal infections. The clinical entities consist of infections arising from any part of the gastrointestinal tract, from the distal esophagus to the colon. These include surgical infections of the bowel, biliary tree, liver, spleen, and pancreas. Virtually all intraabdominal infections are due to multiple microorganisms resident in the gastrointestinal tract; these include aerobes and facultative and obligate anaerobes. Infections are classified as complicated (requiring an operative procedure), uncomplicated (managed medically), and postoperative wound (the operative procedure should be curative, but anti-infective drugs are used to prevent further infection at the site). Clinical criteria are paramount for entry into a study and for evaluation of efficacy. For complicated infections an adequate operation is an important determinant of outcome and needs assessment. Cultures of purulent intraabdominal fluid or abscess material are the only valid microbiologic indicators of infection. The acute physiology and chronic health evaluation score is useful in defining the severity of acute illness. The control regimen should consist of effective, established drugs and surgical procedures for the condition. Duration of therapy for complicated infections is usually 5-14 days; for uncomplicated infections, 3-7 days; and for postoperative wound infection, 2-5 days. Periodic assessment of safety and efficacy must be conducted during therapy. The outcome at final assessment is cure, failure, or indeterminate.

Anti-Infective Agents↗
PubMed1992

Evaluation of new anti-infective drugs for the treatment of acute pelvic infections in hospitalized women. Infectious Diseases Society of America and the Food and Drug Administration.

This set of guidelines deals with evaluation of anti-infective drugs for treatment of acute pelvic infections in hospitalized women. The clinical entities include infectious complications of cesarean section; elective hysterectomy; and septic, incomplete abortion. Conditions including endomyometritis, cuff cellulitis, pelvic cellulitis, parametritis, phlegmon, and pelvic abscesses may arise due to a variety of bacterial species, both aerobic and anaerobic, that comprise the endogenous flora of the lower reproductive tract. Anaerobic bacteria have assumed particular importance, and therapy should be directed against such organisms. The roles of enterococci, chlamydiae, and mycoplasmas remain uncertain. Culture samples must be obtained under conditions assuring minimal vaginal contamination. Before a new drug may be used for treatment of human pelvic infections, considerable information is necessary about its antimicrobial spectrum as well as its safety and efficacy. Placebo-controlled trials are considered unethical. Historical controls may be used, but concurrent active control comparative trials are preferred. Parenteral administration is recommended for at least the initial 4 days of therapy, but orally administered drugs may be evaluated for completion of longer courses. The expected cure rate is approximately 90%. Uncomplicated infections should be treated for at least 4 days; more complicated infections may require prolonged therapy. Although clinical cure is paramount, microbiologic response must also be taken into account. In the final assessment, outcome will be classified as cure, failure, or indeterminate.

Acute Disease↗
PubMed1992

Evaluation of new anti-infective drugs for the treatment of acute pelvic inflammatory disease. Infectious Diseases Society of America and the Food and Drug Administration.

Pelvic inflammatory disease (PID) is a syndrome unrelated to pregnancy or surgery and characterized by lower abdominal pain and tenderness, cervical motion tenderness, and adnexal tenderness. Fever, leukocytosis, and the results of laboratory tests are used to support the diagnosis. Participants in clinical trials should be stratified into two groups: those with and those without tubo-ovarian abscess--i.e., those with complicated and those with uncomplicated PID. Diagnostic studies and treatment should be directed at four major groups of pathogens: Neisseria gonorrhoeae, Chlamydia trachomatis, anaerobic bacteria, and facultative bacteria such as Escherichia coli. Women requiring hospitalization should generally be treated as inpatients for at least 4-7 days; outpatient therapy should then be instituted to complete a 14- to 21-day course. Clinical and laboratory evaluations should be conducted daily during hospitalization and both 2-4 days and 2-4 weeks after the completion of therapy.

Acute Disease↗
PubMed1990

Activation of neutrophils by cachectin/tumor necrosis factor: priming of N-formyl-methionyl-leucyl-phenylalanine-induced oxidative responsiveness via receptor mobilization without degranulation.

Human recombinant cachectin/tumor necrosis factor (TNF) was shown to prime neutrophils (PMNs), in a dose-dependent fashion, for subsequent oxidative responsiveness toward n-formyl-methionyl-leucyl-phenylalanine (FMLP). One basis for this phenomenon appeared to be TNF-mediated FMLP receptor mobilization. The maximal observed priming response was associated with a nearly twofold increase in the expression of PMN FMLP surface receptors, without changes in receptor affinity. Priming was not seen following stimulation with phorbol myristate acetate, possibly eliminating a role for the protein kinase C-dependent transductional components of FMLP-induced oxidative activity in the priming process. FMLP receptor mobilization occurred without significant degranulation as evident by an absence of increased granular enzyme release. These data support a potential role of macrophage-derived TNF in the augmentation of PMN host-defense during infectious and inflammatory challenge. TNF-mediated PMN oxidative priming may also promote oxidant tissue injury as seen in septic shock, adult respiratory distress syndrome, and multiple system organ failure.

Adult↗
PubMed1990

Complement activation and lung permeability during cardiopulmonary bypass.

Pulmonary dysfunction after cardiopulmonary bypass has been attributed to the damaging effects of complement activation on the lung. To further explore this phenomenon, we measured plasma levels of activated complement components (radioimmunoassay), assessed neutrophil n-formyl-methionyl-leucyl-phenylalanine (FMLP) receptor status (radioligand saturation binding assay), and quantified pulmonary epithelial permeability as radioaerosol lung clearance of technetium 99m-labeled diethylenetriamine pentaacetic acid in a series of 8 patients undergoing cardiopulmonary bypass. Significant elevations of plasma C3adesArg, C4adesArg, and C5adesArg levels were seen just after CPB, indicating activation of both the classic and alternate complement pathways. Neutrophil activation was evident as increased expression of neutrophil FMLP surface receptors after bypass. Despite the presence of complement and neutrophil activation, increased pulmonary epithelial permeability was not seen. These data support the hypothesis that complement and neutrophil activation during cardiopulmonary bypass is not associated with acute lung injury, at least not pulmonary epithelial injury. One can therefore infer that increased pulmonary epithelial permeability in patients at high risk for and experiencing sepsis-induced and trauma-induced adult respiratory distress syndrome may be due to factors other than complement and neutrophil activation.

Capillary Permeability↗
PubMed1990

Results of a multicenter trial comparing imipenem/cilastatin to tobramycin/clindamycin for intra-abdominal infections.

We designed a multicenter study to compare tobramycin/clindamycin to imipenem/cilastatin for intra-abdominal infections. We included the Acute Physiology and Chronic Health Evaluation (APACHE II) index of severity and excluded patients without established infection. Two hundred ninety patients were enrolled, of whom 162 were evaluable. Using logistic regression to analyze both outcome at the abdominal site of infection and outcome as mortality, we found a significant correlation for both with APACHE II score (p less than 0.0001 for both). Next we analyzed the residual effect of treatment assignment and found a significant improvement in outcome for imipenem/cilastatin-treated patients (p = 0.043). The differences in outcome were explained by a higher failure rate for patients with gram-negative organisms for tobramycin/clindamycin-treated patients (p = 0.018). This was reflected in a significantly higher incidence of fasciitis requiring reoperation and prosthetic fascial replacement. Maximum peak tobramycin levels were analyzed for 63 tobramycin/clindamycin patients harboring gram-negative organisms. For failures the maximum peak was 6.4 +/- 1.9 micrograms/mL, and time to maximum peak was 4.6 +/- 5.2 days. For successes the maximum peak was 6.1 +/- 1.7 micrograms/mL, occurring at 3.8 +/- 2.6 days. This study supports inclusion of severity scoring in statistical analyses of outcome results and supports the notion that imipenem/cilastatin therapy improves outcome at the intra-abdominal site of infection as compared to a conventionally prescribed amino-glycoside-based regimen.

Abscess↗
PubMed1990

Neutrophil disorders in burn injury: complement, cytokines, and organ injury.

Because of the association of burn injury with subsequent bacterial infection, numerous studies have been performed characterizing neutrophil function in burn injury. These studies provide a picture of intravascular complement activation, neutrophil-C5a interactions, and consequent disordered cellular function. Neutrophil dysfunction includes suppressed random and C5a-directed migration and hyperresponsiveness to oxidative stimuli. These observations do not explain the histologic and functional involvement of neutrophils in ARDS and perhaps other organ failure states. Circumstantial and extrapolated information suggests that macrophage-lineage cells function as regulators of neutrophil function within matrix environments in burn injury. Elevated endotoxin levels have been found in burned patients, which would support the notion of endotoxin-stimulated monocytes/macrophages as inducing neutrophil migration into connective tissue matrices (LTB4 and IL-8), inducing prolonged oxidant production (TNF-alpha, GM-CSF), and inducing neutrophil release of regulatory substances from neutrophils (G-CSF). This information suggests a variety of experimental approaches to testing this hypothesis.

Burns↗
PubMed1989

Production and release of C3 by cultured monocytes/macrophages isolated from burned, trauma, and septic patients.

The release of C3 under various conditions by cultured monocytes/macrophages isolated from burned, trauma, and septic trauma patients was determined. When monocytes were cultured for up to 14 days there was no difference in production and release of C3 by normals and patients; C3 production rose slowly at first then rose rapidly from 8-14 days of culture. C3 production continued for up to 28 days of culture. When lymphocytes were present with the monocytes for the first 24 hr of culture there were differences in C3 production by normal and patient cells at various times of culture. There were differences in C3 release by patients' 24 hour-cultured cells at certain postburn and injury days. Macrophages from burned patients released less C3 than normal cells and macrophages from septic trauma patients released more C3 than normal cells.

Burns↗
PubMed1988

Characterization of N-formyl-methionyl-leucyl-phenylalanine receptors on human neutrophils. Effects of isolation and temperature on receptor expression and functional activity.

The study of polymorphonuclear neutrophil (PMN) surface receptor expression provides a means for the assessment of PMN function and state of cellular activation. In this study, we characterized binding of the chemotactic peptide FMLP to whole PMN, with particular attention to those variables that may account for the wide variation reported in the literature. These included avoidance of oxidized FMLP as a radioligand contaminant, determination of the optimal cold ligand concentration necessary for achieving minimal nonspecific binding throughout the range of radioligand concentrations used in saturation experiments (greater than or equal to 5 x 10(-5) M), avoidance of radioligand concentrations that equal or exceed receptor saturation and are not suitable for Scatchard analysis (greater than or equal to 60 to 80 nM), and avoidance of inadvertent receptor mobilization due to room temperature PMN isolation techniques and cell warming. PMN isolated and maintained at 4 degrees C expressed a single, high affinity population of FMLP receptors (approximately 6000 receptors per cell) with a KD of 15.5 nM. These characteristics, and in particular the single-affinity nature of the expressed FMLP receptor site, were derived from saturation experiments and confirmed with agonist competition studies. PMN subjected to room temperature isolation or 37 degrees C warming exhibited a 2.5-fold increase in FMLP receptor expression (approximately 15,000 receptors per cell) without changes in receptor affinity. These latter PMN, in correlation with increased receptor expression, had increased initial, maximal rates of FMLP-induced superoxide generation (10.2 vs 6.3 nmol/min/10(6) PMN for cells isolated and maintained at 4 degrees C) as a manifestation of their functional activation. The avoidance of inadvertent cellular activation during PMN isolation is essential to studies of PMN function, activation and the role of FMLP receptor expression/mobilization in these processes.

Binding, Competitive↗
PubMed1988

Neutrophil activation in sepsis. The relationship between fmet-leu-phe receptor mobilization and oxidative activity.

To elucidate further the manifestations and mechanisms of neutrophil (PMN) activation, PMNs from control and septic subjects were studied at baseline and under conditions of graded, in vitro activation. At baseline (4 degrees C PMN isolation), septic-derived PMNs were activated, as manifested by twofold increases in fmet-leu-phe (FMLP)-induced oxidative activity and concomitant FMLP surface receptor expression, compared with controls. Following degranulationlike maximal activation (phorbol myristate acetate pretreatment), both PMN populations exhibited maximal FMLP-induced oxidative priming and receptor up-regulation. However, following exudation-like moderate activation (37 degrees C pretreatment), control PMNs underwent significant receptor mobilization and oxidative priming but septic-derived PMNs exhibited oxidative deactivation (decreased FMLP-induced oxidative activity) without changes in FMLP receptor expression. Our data support the theory that while circulating PMNs in sepsis may promote oxidant-related microvascular lung injury, their oxidative deactivation following transpulmonary exudation (simulated by 37 degrees C pretreatment) may underlie the increased incidence of pulmonary infections seen in sepsis-induced adult respiratory distress syndrome.

Bacterial Infections↗
PubMed1988

Use of new beta-lactam antibiotics for surgical infections.

The availability of beta-lactam antibiotics with extended spectra of activity against organisms commonly seen in surgical infections suggests that aminoglycoside-based therapy is no longer needed for most such community-acquired infections. The primary problems with specific beta-lactams are lack of activity against Bacteroides species and variable activity against Pseudomonas aeruginosa and enterococci. The pharmacokinetic properties of the newer beta-lactams vary considerably. This variation suggests specific settings in which these properties may be taken advantage of to improve clinical outcome.

Anti-Bacterial Agents↗
PubMed1987

Complement-mediated neutrophil activation in sepsis- and trauma-related adult respiratory distress syndrome. Clarification with radioaerosol lung scans.

Complement-mediated neutrophil activation (CMNA) has been proposed as an important pathogenic mechanism causing acute microvascular lung injury in the adult respiratory distress syndrome (ARDS). To clarify the relationship between CMNA and evolving lung injury, we studied 26 patients with multiple trauma and sepsis within 24 hours of risk establishment for ARDS. Pulmonary alveolar-capillary permeability (PACP) was quantified as the clearance rate of a particulate radioaerosol. Seventeen patients (65%) had increased PACP (six developed ARDS) while nine (35%) had normal PACP (none developed ARDS; clearance rates of 3.4%/min and 1.5%/min, respectively). These patients, regardless of evidence of early lung injury, had elevated plasma C3adesArg levels and neutrophil chemotactic desensitization to C5a/C5adesArg. Plasma C3adesArg levels correlated weakly, but significantly, with PACP. Thus, CMNA may be a necessary, but not a sufficient, pathogenic mechanism in the evolution of ARDS.

Adult↗
PubMed1987

Design and conduct of antibiotic trials. A report of the Scientific Studies Committee of the Surgical Infection Society.

Several recent publications have identified important methodologic problems in the design and conduct of antimicrobial trials in surgery. Developed by consensus of the members of the Scientific Studies Committee of the Surgical Infection Society, this report provides broad guidelines for the construction of antimicrobial trials. The central issues identified include pretrial definition of study purpose, entry criteria, assignment device, and statistical analysis. These issues are fundamental in designing studies with an acceptable likelihood of finding differences among those antimicrobial regimens at least risk to the study subjects. The importance of stratifying patients on the basis of background condition, disease, and severity of illness is stressed. The inclusion in a study of variables that enhance the statistical power and, therefore, the believability of this study is stressed as an important means of clarifying substantial differences between therapies.

Abdomen↗
PubMed1987

Surface receptor mobilization in complement-mediated neutrophil activation: characterization and effects of methylprednisolone.

Complement-mediated neutrophil activation (CMNA) is an important host defense mechanism that is essential for effective neutrophil (PMN) proinflammatory activity. It has also been implicated as a pathogenic mechanism contributing toward the development of adult respiratory distress syndrome. Utilizing zymosan-activated serum pretreatment as an in vitro model for CMNA, we characterized the effects of CMNA on PMN superoxide (SO) production and N-formyl-methionyl-leucyl-phenylalanine (FMLP) receptor status. CMNA was associated with a 132 +/- 38% increase in FMLP-induced SO generation and a 110 +/- 30% increase in FMLP receptor expression. Methylprednisolone pretreatment prevented both the FMLP receptor mobilization and the SO priming effects of CMNA. These data support a concept that FMLP receptor mobilization is an important element in the PMN activation process. In addition, blocking this phenomenon may have clinical significance in attempts to modulate the potential damaging effects of the increased PMN oxidative metabolism associated with CMNA.

Complement System Proteins↗
PubMed1987

Increased pulmonary alveolar-capillary permeability in patients at risk for adult respiratory distress syndrome.

Two methods for predicting adult respiratory distress syndrome (ARDS) were evaluated prospectively in a group of 81 multitrauma and sepsis patients considered at clinical high risk. A popular ARDS risk-scoring method, employing discriminant analysis equations (weighted risk criteria and oxygenation characteristics), yielded a predictive accuracy of 59% and a false-negative rate of 22%. Pulmonary alveolar-capillary permeability (PACP) was determined with a radioaerosol lung-scan technique in 23 of these 81 patients, representing a statistically similar subgroup. Lung scanning achieved a predictive accuracy of 71% (after excluding patients with unilateral pulmonary contusion) and gave no false-negatives. We propose a combination of clinical risk identification and functional determination of PACP to assess a patient's risk of developing ARDS.

Adult↗
PubMed1987

A review of antibiotic prophylaxis for open fractures.

A review of the literature strongly supports the use of antibiotic prophylaxis in open fracture management. Because of their broad spectrum of activity, cephalosporins are the drugs of choice in cases of orthopaedic trauma. The extent of the injury determines the appropriate agent and the length of time it should be given. Patients with Type 1 or Type 2 fractures require only brief treatment (one preoperative and two postoperative doses) with an agent that has good antistaphylococci activity. Cephalothin, cefazolin, cefamandole or cefuroxime are recommended. Type 3 fractures present a much greater problem because of the risk of gram-negative infection. The marked activity of cefuroxime, cefamandole, and cefotaxime against these organisms recommends their use in such cases. Combination regimens with aminoglycosides require further study to define added efficacy and to define appropriate dosing regimens. We advocate that antibiotic prophylaxis should be given as soon as possible to all patients with open fractures and Type 3 fractures, and that prophylaxis should continue until 48 hours after adequate soft tissue coverage is achieved.

Anti-Bacterial Agents↗