Oxacillin or cefalotin treatment of hospitalized children with cellulitis.

Cellulitis is an important cause of hospitalization in pediatrics. Because Staphylococcus aureus is the main pathogen of cellulitis, medicinal therapeutics should take the changing resistance profile of this organism into consideration. The aim of this study was to evaluate the progression and outcomes of children hospitalized for cellulitis and treated with oxacillin or cefalotin. This retrospective cohort study enrolled 218 children, hospitalized between 2001 and 2008 in Salvador, Northeast Brazil. All were diagnosed with cellulitis and treated with oxacillin or cefalotin (≥100 mg/kg/day). The median age was 2 years and 56.9% were males. Frequencies of signs and symptoms used in the clinical diagnoses were as follows: swelling (91.3%), redness (81.7%), warmth (47.2%), and tenderness (31.7%). All patients were discharged due to clinical recovery and the mean length of hospitalization was 7 ± 4 days. None of the patients died, needed intensive care, or had sequelae. By comparing the daily frequency of clinical findings during hospitalization, significant decreases were found in the frequencies of fever (admission day [42.2%], first day [20.8%], second day [12.9%], third day [8.3%], fourth day [6.1%]), toxemia, irritability, somnolence, vomiting, tachycardia, and need for intravenous hydration. In conclusion, oxacillin or cefalotin remain the drugs of choice for treating uncomplicated cellulitis in regions where community-acquired methicillin-resistant S. aureus is infrequent (<10%).

[Experimental approach to the prophylaxis and treatment of acute lung injury syndrome with proteinase inhibitors and corvitin]. / Eksperymental'ni pidkhody do profilaktyky ta likuvannia syndromu hostroho ushkodzhennia lehen' z vykorystanniam inhibitoriv proteïnaz i korvitynu.

The results of a combined study of the proteolysis on a model of post-ischemic toxemia in rats showed a decrease in antiproteinase potential and an activation of proteolysis. The activation of proteolysis and inhibition of antiproteinases was observed not only in the blood, but also in the bronchoalveolar secretion. Those changes were accompanied with the changes in the morphological structure of the lungs. The data obtained have shown a high effectiveness of proteinase inhibitor (contrical) and an antioxidant of flavonoid group (corvetine). Those drugs decreased the morphological changes in the lungs and prevented the development of imbalance in proteinase-inhibitor system. The prophylactic effect was more considerable when both drugs were used in a combined way.

Reduction in intestinal leukocyte adherence in rat experimental endotoxemia by treatment with the 21-aminosteroid U-74389G.

OBJECTIVES: To investigate leukocyte adherence in intestinal venules in experimental endotoxemia after treatment with the 21-aminosteroid U-74389G. DESIGN AND SETTING: Prospective, randomized, controlled animal study in an experimental laboratory. SUBJECTS: Twenty-one male Wistar rats weighing 190 +/- 40 g. INTERVENTIONS: The rats were divided equally into three groups: (a) control group, (b) endotoxemia (5 mg/kg lipopolysacharide from Escherichia coli O55:B5), and (c) endotoxemia and U-74389G administration 30 min before (3 mg/kg) and 60 min after endotoxin challenge (1.5 mg/ kg). MEASUREMENTS AND MAIN RESULTS: The distal small intestine of the animals was examined using intravital fluorescence videomicroscopy 2 h after endotoxin challenge. Leukocytes were stained in vivo by means of rhodamine 6G. In the endotoxemic animals we observed a fourfold increase in the count of firmly adherent leukocytes in submucosal post-capillary and collecting venules. Treatment with the 21-aminosteroid U-74389G significantly attenuated the count of sticking leukocytes in the collecting venules (control, 61 +/- 10 cells/mm2; lipopolysaccharide, 237 +/- 42 cells/mm2; U-74389G 125 +/- 9 cells/mm2; p < 0.05). In these venules leukocyte rolling behavior was comparable to that in the control group without endotoxin challenge. CONCLUSIONS: Administration of U-74389G, which has radical scavenging properties, attenuates leukocyte adherence in selected populations of intestinal venules which is found increased during endotoxemia. Thus, 21-aminosteroids may have an impact in the treatment of endotoxin-induced intestinal injury.

Intestinal toxemia botulism in two young people, caused by Clostridium butyricum type E.

Two unconnected cases of type E botulism involving a 19-year-old woman and a 9-year-old child are described. The hospital courses of their illness were similar and included initial acute abdominal pain accompanied by progressive neurological impairment. Both patients were suspected of having appendicitis and underwent laparotomy, during which voluminous Meckel's diverticula were resected. Unusual neurotoxigenic Clostridium butyricum strains that produced botulinum-like toxin type E were isolated from the feces of the patients. These isolates were genotypically and phenotypically identical to other neurotoxigenic C. butyricum strains discovered in Italy in 1985-1986. No cytotoxic activity of the strains that might explain the associated gastrointestinal symptoms was demonstrated. The clinical picture of the illness and the persistence of neurotoxigenic clostridia in the feces of these patients suggested a colonization of the large intestine, with in vivo toxin production. The possibility that Meckel's diverticulum may predispose to intestinal toxemia botulism may warrant further investigation.

[Effectiveness and disposition of the newly developed cephalosporin cefquinome in puerperal septicemia and toxemia in gilts]. / Untersuchungen zur Wirksamkeit und Verträglichkeit des neu entwickelten Cephalosporins Cefquinom bei an puerperaler Septikämie und Toxämie erkrankten Sauen.

Epizootiological, clinical, bacteriological and haematological studies were carried out to assess the effectiveness of the recently developed cephalosporin preparation Cefquinome in the treatment of the puerperal septicaemia and toxaemia syndrome. Cefquinome was administered at three different doses (1, 2 and 4 mg/kg BW) to 188 sows with feverish puerperal illness. Amoxicillin (7 mg/kg BW) was used as a control drug. In 41% of cases endometritis was a monoinfection whereas in 70% of mammary infections mixed infections were diagnosed. Results showed that for therapy of puerperal septicaemia and toxaemia Cefquinome at doses of 2 mg/kg BW and 4 mg/kg BW is clearly more effective than the control drug Amoxicillin and Cefquinome at its lowest dose of 1 mg/kg BW.

Deliganded albumin as a liquid adsorbent in the treatment of burn toxemia.

A new generation of synthetic carbon adsorbents was used in production of deliganded human serum albumin preparation. Thermal effects of officinal and deliganded albumin interaction with specific chemical markers were analyzed by flow microcalorimetry. The results demonstrated a 2.5-fold increase of the complexing ability for the deliganded one. The detoxifying potentials of deliganded albumin were studied in comparison with officinal preparation in rats with burn toxemia after IIIB-IV degree thermal injury and in model experiments with blood serum of patients after severe thermal burn. The transfusion of a 5% officinal albumin solution in rats 1 h after burn trauma resulted in a decrease of serum and liver cytosols cytotoxicity 2.2 and 2.4 times, respectively, in comparison with those of burned rats. After deliganded albumin transfusion the cytotoxic activity of blood serum dropped 8.5 times and that of the liver cytosols 18.5 times. The incubation of blood serum of injured patients with equal amounts of a 5% solutions of officinal or deliganded albumin resulted in a fall of the cytotoxicity level and the growth of binding ability. A comparative analysis of detoxifying potentials of albumin preparations has unambiguously demonstrated deliganded albumin advantages.

A novel inhibitor of bacterial endotoxin derived from cinnamon bark.

A substance that inhibits the activity of bacterial endotoxin (LPS) was found in cinnamon bark. The inhibitor, extracted from dry cinnamon bark with 67% ethanol/water, was purified by using Limulus gelation activity as an indicator of endotoxin activity. The inhibitor suppressed the activity of the LPS when it was mixed with the inhibitor prior to the assay. The reduction of the LPS activity depended on the concentration of both the inhibitor and LPS when mixed, and also on the incubation time. The inhibitor suppressed the activity of all LPS and lipid A preparations tested regardless of the origin of the bacteria. The inhibitor alone did not affect the Limulus system. These results indicate that the inhibition was caused by direct interaction of the inhibitor with the LPS molecule. Furthermore the inhibitor abrogated the pyrogenicity of the LPS. Although it is uncertain whether the inhibitor actually plays a role in the defense mechanism in cinnamon bark, this is the first report that an inhibitor of bacterial endotoxin exists in a plant.

Low lipid concentrations in critical illness: implications for preventing and treating endotoxemia.

OBJECTIVES: To determine the prevalence and clinical significance of hypolipidemia found in critically ill patients, and whether the addition of a reconstituted lipoprotein preparation could inhibit the generation of tumor necrosis factor-alpha (TNF-alpha) in acute-phase blood taken from these patients. SETTING: Surgical intensive care unit (ICU) of a large urban university hospital. DESIGN: Prospective case series. PATIENTS: A total of 32 patients with a variety of critical illnesses had lipid and lipoprotein concentrations determined. Six patients and six age- and gender-matched control subjects had whole blood in vitro studies of the effect of lipoprotein on lipopolysaccharide mediated TNF-alpha production. INTERVENTIONS: Blood samples were drawn on admission to the ICU and over a subsequent 8-day period. MEASUREMENTS AND MAIN RESULTS: Mean serum lipid and lipoprotein values obtained from patients within 24 hrs of transfer to the surgical ICU were extremely low: mean total cholesterol was 117 mg/dL (3.03 mmol/L), low-density lipoprotein cholesterol 71 mg/dL (1.84 mmol/L), and high-density lipoprotein cholesterol 25 mg/dL (0.65 mmol/L). Only the mean triglyceride concentration of 105 mg/dL (1.19 mmol/L), and the mean lipoprotein(a) concentration of 25 mg/dL (0.25 g/L) were within the normal range. During the first 8 days following surgical ICU admission, there were trends toward increasing lipid and lipoprotein concentrations that were significant for triglycerides and apolipoprotein B. Survival did not correlate with the lipid or lipoprotein concentrations, but patients with infections had significantly lower (p = .008) high-density lipoprotein cholesterol concentrations compared with noninfected patients. Lipopolysaccharide-stimulated production of TNF-alpha in patient and control blood samples was completely suppressed by the addition of 2 mg/mL of a reconstituted high-density lipoprotein preparation. CONCLUSIONS: Patients who are critically ill from a variety of causes have extremely low cholesterol and lipoprotein concentrations. Correction of the hypolipidemia by a reconstituted high-density lipoprotein preparation offers a new strategy for the prevention and treatment of endotoxemia.

Lidocaine attenuates the hypotensive and inflammatory responses to endotoxemia in rabbits.

OBJECTIVE: To assess the effects of lidocaine on the hemodynamic and inflammatory responses to Escherichia coli endotoxemia in rabbits. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University laboratory. SUBJECTS: Twenty-seven female Japanese rabbits, anesthetized with urethane and ventilated mechanically. INTERVENTIONS: Animals were randomly assigned to one of three groups: a) endotoxemic control group (n = 9), receiving intravenous Escherichia coli endotoxin (0.5 mg/kg bolus) via the mesenteric vein; b) laparotomy control group (n = 9), treated identically to the endotoxemic control group, except for substitution of 0.9% saline for endotoxin; and c) lidocaine-treated group (n = 9), treated identically to the endotoxemic controls and additionally, intravenous lidocaine (3 mg/kg bolus, followed by infusion at 2 mg/kg/hr) was administered immediately after endotoxin MEASUREMENTS AND MAIN RESULTS: We compared hemodynamics, blood gases, and microscopic findings of lung tissue obtained at necropsy in each group. Laparotomy alone had a minimal effect on the parameters and findings. Endotoxin injection decreased mean systolic arterial pressure from 135 +/- 6 (SD) to 95 +/- 25 mm Hg (p < .05) and increased the mean base deficit from -1.2 +/- 1.8 to -14.4 +/- 4.2 mmol/L (p < .05), and caused the infiltration of neutrophils into the lungs. Lidocaine administration abolished the hypotension and attenuated the increase the base deficit to -9.5 +/- 2.1 mmol/L (p < .05) and the cellular infiltration in comparison with endotoxemic controls. CONCLUSIONS: Lidocaine attenuated the hemodynamic and inflammatory responses to endotoxemia in rabbits. Findings suggest that lidocaine administration may prevent the development of hypotension and metabolic acidosis during endotoxemia.

The effects of glibenclamide, a blocker of K+ ATP-sensitive potassium channels, on diaphragmatic fatigue during endotoxaemia in pigs.

An in vivo porcine model of endotoxaemia was used to study the effects of glibenclamide, a K+ ATP-sensitive potassium channel blocker. Escherichia coli lipopolysaccharides (LPS, 70 micrograms/kg, i.v., as a bolus) were infused into anaesthetized, mechanically ventilated, indomethacin-treated pigs. After 120 min of endotoxaemia, glibenclamide was administered (10 mg/kg, i.v., over 5 min) to half the pigs. The strength at different frequencies of stimulation (10, 20, 30, 50 Hz, 20 V,) 1 s) and the endurance capacity (10 Hz, 20 V, 30 s) of the diaphragm were evaluated after 120 min of endotoxaemia and 5, 10, 20 and 30 min after drug infusion. Glibenclamide transiently increased the blood pressure without changing the decreased cardiac output and at the same time further impaired the diaphragmatic activity. The reduced ability of the diaphragm to generate force in response to different electrical stimulations was shown by a significant reduction in strength. The endurance index decreased 5 min after glibenclamide infusion, returning to the pre-glibenclamide values by 150 min. These results indicate that glibenclamide modifies the activity of vascular smooth muscle and of the diaphragm.

[Ofloxacin in comprehensive treatment of infections in burn patients]. / Ofloksatsin v kompleksnom lechenii infektsii u obozhzhennykh.

The experience with ofloxacin in the prophylaxis and treatment of infected burn wounds in 40 patients was investigated. High clinical and microbiological efficacy of the drug was stated (82.5 and 83 per cent respectively). The highest efficacy of ofloxacin was observed when the burned area did not exceed 25 per cent of the body surface. It was concluded that the prophylactic use of the drug during acute burn toxemia was not expedient.

Effect of parenteral antioxidants on adrenal pathobiology and leukocytes in hyperammonaemic toxaemia.

Infestation of sheep by L. cuprina larvae produces extensive skin wounds, severe dermatitis, hyperammonaemia and stress with adrenal necrosis and haemmorhage. In infested sheep, intramuscular (im) injections of Dl-Alpha tocopherol induced wool shedding and Desferrioxamine im prevented declines in white blood cells (WBC). In further trials, daily im injections of sodium ascorbate with Dl-alpha tocopherol, desferrioxamine and oral butylated-hydroxyanisole prevented adrenal damage and induced adrenocortical hypertrophy of the zona fasciculata. The treatment boosted the levels of mature and juvenile neutrophils, and blood glucose. Increases in toxic ammonia levels were correlated with increased toxic and band neutrophils, and globulin levels in treated sheep and toxic neutrophils in non-treated sheep. Decreases in serum zinc were correlated with declining lymphocytes and globulin levels. The results suggested that antioxidants protect and enhance adrenal activation in hyperammonaemic toxaemia. The changes in WBC, globulins and glucose were consistent with protected adrenocortical activation.

Triglyceride-rich lipoproteins improve survival when given after endotoxin in rats.

BACKGROUND: Triglyceride-rich lipoproteins have been shown to bind bacterial endotoxin and inhibit its activity in vitro and to protect animals from death when administered before a lethal injection of endotoxin. We now demonstrate that triglyceride-rich lipoproteins can neutralize the toxic effects of endotoxin already in circulation. METHODS: Rats were infused with a lethal dose of endotoxin, followed at various time intervals by an infusion of either mesenteric lymph containing nascent chylomicrons (1 gm chylomicron triglyceride/kg) or an equal volume of normal saline solution. Survival was measured at 48 hours. The experiment was then repeated, substituting the synthetic triglyceride-rich lipid emulsion (1 gm/kg) for chylomicrons. We also measured the clearance and tissue distribution of radioiodinated endotoxin in rats treated subsequently with chylomicrons or saline solution. RESULTS: Chylomicron infusions significantly improved survival when given up to 30 minutes after a lethal dose of endotoxin (p < 0.05). Chylomicrons accelerated endotoxin clearance from the blood and increased endotoxin uptake by the liver. The synthetic triglyceride-rich lipid emulsion significantly improved survival when given up to 15 minutes after a lethal dose of endotoxin (p < 0.05). CONCLUSIONS: Triglyceride-rich lipoproteins and synthetic triglyceride-rich lipid emulsions significantly improve survival of rats when given after a lethal dose of endotoxin. Lipoprotein treatment accelerates endotoxin clearance to the liver, which may account for the observed protection. These data suggest a possible therapeutic role for triglyceride-rich lipoproteins or synthetic lipid emulsions in the treatment of the endotoxemia of gram-negative sepsis.

Gastric and extragastric actions of the histamine antagonist ranitidine during posttraumatic sepsis.

BACKGROUND: Histamine H2 antagonists (e.g., ranitidine) are generally thought to specifically reduce gastric acid secretion and are commonly used for stress ulcer prophylaxis in critically ill patients because of their efficacy and safety profile. A few reports suggest that ranitidine might also bind to extragastric sites and/or act as an immunomodulator. The potential effects on posttraumatic sepsis are unknown. METHODS: Mongrel pigs (n = 24) were anesthetized with fentanyl, injured by a 10 kg steel bar dropped from a height of 1 m onto the fleshy portion of the posterior thigh, and then 35% of their blood volume was drained through the arterial catheter. All the shed blood plus two times the hemorrhage volume as lactated Ringer's solution was infused after a 1-hour shock period. Either vehicle or ranitidine (1.5 mg/kg) was intravenously administered at the time of resuscitation and every 12 hours thereafter in a blinded fashion. After 72 hours a septic challenge was administered (15 micrograms/kg Escherichia coli lipopolysaccharide [LPS] x 30 min). Serial gastroscopy, gastric pH, hemodynamics, leukocyte counts, cortisol, and tumor necrosis factor were recorded for 180 minutes after LPS. RESULTS: Immediately before LPS all hemodynamic variables were identical between treatments, but gastric pH was slightly higher and stress gastritis was marginally lower with ranitidine. LPS caused profound leukopenia and a hyperdynamic circulatory response (i.e., tachycardia, increased cardiac output, and decreased peripheral vascular resistance at relatively constant blood pressure); these changes were not altered by ranitidine. Gastric pH remained elevated after LPS with ranitidine, but LPS-induced gastritis was not modified. Ranitidine delayed the LPS-induced ventilation-perfusion imbalance and attenuated the peak increase in the proinflammatory cytokine, tumor necrosis factor, without altering its antiinflammatory opponent, cortisol. Similar changes were observed in four additional animals treated with cimetidine. The proportion of circulating neutrophils and lymphocytes was slightly altered 180 minutes after LPS, but there was no obvious effect on T lymphocytes in vivo, and no effect on the LPS-induced increase in neutrophil CD18 expression in vitro was seen. CONCLUSIONS: (1) Ranitidine increased gastric pH, which blunted the stress gastritis caused by trauma but not that caused by LPS; (2) ranitidine delayed the early LPS-evoked pulmonary changes and reduced the tumor necrosis factor spike, which is consistent with a favorable immunomodulatory action that has been reported in patients who are critically ill or are undergoing an elective abdominal surgical procedure; (3) the mechanism is probably related to H2 receptor antagonism rather than to a nonspecific side effect of ranitidine, which suggests that histamine may have a previously unrecognized role in posttraumatic septic responses; and (4) the site of action is probably not in the heart or peripheral resistance vessels, but salutary effects on circulating lymphocytes or neutrophils cannot be excluded.

[Experimental study on compatible application of heat-clearing and detoxifying drugs with blood circulation improving drugs].

The article describes the effectiveness of compatible application of heat-clearing and detoxifying drugs with blood circulation improving drugs to the animal model with endotoxemia and nonspecific inflammation. The compatible application reduces PGE2, endotoxin blood concentration and reduced viscosity of whole blood, decreases Evans blue extravasation volume and pes swelling percentage, increases serum cortisol content and enhances fibrinolytic activity. The experimental result shows that in most cases these two drugs work better when used in combination which implies that compatible application is more effective in detoxification, antiinflammation and inflammation recovery.

[Early radiation-induced toxemia and effectiveness of its correction with aminodez and gluconeodez]. / Ranniaia luchevaia toksemiia i éffektivenost' ee korrektsii aminodezom i gliukoneodezom.

The experiments on irradiated rats (LD90/30) and dogs (LD70/45) have shown that three administrations of aminodez or gluconeodez in a dose 10 mg/kg (3, 24 and 48 hours after the exposure) lowered radiotoxins levels (malonic dialdehyde, middle-molecular peptides), promoted stabilization of cellular membranes, enhanced activity of the body's detoxicating systems. In irradiated rats early detoxicating therapy with aminodez and gluconeodez raised survival by 40%.

Bactericidal/permeability-increasing protein ameliorates acute lung injury in porcine endotoxemia.

Bactericidal/permeability-increasing protein (BPI), a cationic protein isolated from human neutrophils, binds lipopolysaccharide (LPS), kills gram-negative bacteria, and neutralizes many of the effects of LPS in vitro and in vivo. We hypothesized that a recombinant 23-kDa NH2-terminal fragment of BPI (BPI23) would reduce acute lung injury in endotoxemic pigs. At -18 h, pigs received an intravenous priming dose of LPS (20 micrograms/kg). Anesthetized ventilated swine were randomized to receive 1) no further treatment (n = 4); 2) LPS (250 micrograms/kg over 50 min) and BPI23 (3-mg/kg bolus and 3 mg/kg over 60 min) (n = 6); or 3) LPS and thaumatin, a cationic protein devoid of LPS neutralizing activity that has a molecular mass and isoelectric point that are similar to that of BPI23 (n = 7). BPI23 treatment significantly ameliorated LPS-induced hypoxemia, functional upregulation of opsonin receptors on circulating phagocytes, and alveolitis but had no effect on the elaboration of tumor necrosis factor-alpha or thromboxane A2. The salutory effects of BPI23 on acute lung injury in endotoxemic pigs may be mediated, at least in part, by inhibition of direct activation of phagocytes by LPS.

Ursodeoxycholic acid modifies gut-derived endotoxemia in neonatal rats.

We developed a model for the translocation of intraluminal endotoxin in the neonatal animal and used it to examine the capacity of a nonhepatotoxic bile acid, ursodeoxycholic acid (UDCA), to modify endotoxin translocation and cytokine response. Three-d-old Sprague-Dawley rats were randomized to receive enterally either no drug, lipopolysaccharide (LPS, 1 mg/animal), or UDCA (400 micrograms/animal) alone, or UDCA followed by LPS 1 h later. One h after LPS administration, the rats were killed and plasma endotoxin and tumor necrosis factor (TNF) were measured. Control animals had low circulating endotoxin (21.2 +/- 7.6 endotoxin units) and TNF (0.06 +/- 0.02 ng/mL). Enteral administration of LPS 1 h before the rats were killed resulted in significant elevation of endotoxin (249.5 +/- 71.3, p = 0.008) and TNF (3.6 +/- 1.3, p = 0.019). UDCA alone did not alter endotoxin levels (8.7 +/- 2.1). UDCA 1 h before LPS prevented the rise in endotoxin (38.9 +/- 11.2 endotoxin units) and TNF (0.2 +/- 0.05) significantly. Chenodeoxycholic acid was studied in a similar group of experiments and prevented neither the translocation of LPS nor the development of increased TNF levels in animals receiving LPS. In conclusion, LPS can cross the intestinal barrier in the normal neonatal rat. UDCA, administered before LPS, can decrease the translocation of LPS and prevent the cytokine response as measured by TNF levels. We speculate that UDCA, administered prophylactically, might reduce morbidity in clinical conditions leading to gut-derived endotoxemia.

Immunological aspects of the effect of pentoxifylline (Trental) (a brief review).

Pentoxifylline (methixanthine derivate) has haemorheological activity, thought to based on its ability to reduce blood viscosity and increase the filterability of blood cells and widely used for the treatment of various types of vascular insufficiency. Recent studies provide evidence for the effect of this drug on immune functions. Pentoxifylline is able to influence in vitro as well as in vivo production of cytokine including tumour necrosis factor alpha. This drug has been shown to attenuate the symptoms of endotoxin shock and adult respiratory distress syndrome. Its beneficial effect on tumour-induced cachexia, organ transplantation and AIDS can widen the indications of clinical administration. Nevertheless, the chronic continuous administration of Pentoxifylline in arterial insufficiency is to be considered due to its potentially enhanced susceptibility to malignant disorders.