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T Calandra

Publications and source records attributed to T Calandra.

At least 73 records · Page 4Linked to original sources
PubMed1992

Teicoplanin versus vancomycin for prophylaxis of experimental Enterococcus faecalis endocarditis in rats.

Teicoplanin was compared with vancomycin for the prophylaxis of experimental Enterococcus faecalis endocarditis in rats. Single intravenous doses of teicoplanin (7 mg/kg of body weight) or vancomycin (15 mg/kg) were given 30 min before bacterial challenge. Two strains of E. faecalis (309 and 1209) isolated from patients with endocarditis were tested. Bacterial inocula ranged from 10(4) (i.e., the inoculum infecting 90% of the control rats [ID90]) to 10(7) CFU/ml. The MICs and MBCs of teicoplanin and vancomycin were, respectively, 0.25 to greater than 128 mg/liter and 2 to greater than 128 mg/liter for strain 309 and 0.5 to greater than 128 mg/liter and 0.5 to greater than 128 mg/liter for strain 1209. Vancomycin prevented endocarditis only in 60% (strain 309) and in 87% (strain 1209) of rats challenged with the smallest bacterial-inoculum size (ID90), whereas teicoplanin prevented endocarditis in 100% of rats challenged with the same inoculum (strain 309; P = 0.05), in 87% of rats challenged with 10 times the ID90 (strain 309; P = 0.02), and in 95% of rats challenged with 100 times the ID90 (strain 1209; P = 0.0003). The combination of teicoplanin plus gentamicin (4 mg/kg) extended the protection to inocula 100 times the ID90 (strain 309; 96% of sterile animals) and 1,000 times the ID90 (strain 1209; 100% of sterile animals). Prevention of endocarditis was likely to be due to a prolonged inhibition of bacterial growth by sustained levels of teicoplanin in serum and not to bacterial killing. Indeed, teicoplanin did not exhibit any bactericidal activity either in vitro (time-kill curves) or in vivo (serum bactericidal activity). Teicoplanin proved to be superior to vancomycin in the prophylaxis of experimental E. faecalis endocarditis in rats.

Animals↗
PubMed1991

Spectrum and treatment of bacterial infections in cancer patients with granulocytopenia.

Bacterial infections remain a frequent cause of morbidity and mortality in cancer patients with granulocytopenia. In recent years the proportion of patients with gram-positive infections, caused mainly by coagulase-negative staphylococci and viridans streptococci, has increased markedly in many institutions. The precise reasons for this recent change in the epidemiology of infection in cancer patients are as yet not fully ascertained. Although less prevalent, gram-negative infections are still the major threat, since they are associated with higher mortality. What constitutes the optimal empirical antibiotic therapy remains a controversial issue. One should however recognize that the results of one particular study may not be relevant to other institutions where the predominant pathogens and the pattern of antibiotic resistance may be different. In addition, the results of studies using various antibiotic regimens should be compared with caution. However, with these limitations in mind, the results of the most recently published studies support the following recommendations: in patients with nonmicrobiologically documented infections, monotherapy with a third-generation cephalosporin or a carbapenem is a safe alternative to combination therapy. For gram-negative bacteremia, combined therapy with an extended-spectrum beta-lactam antibiotic and an aminoglycoside appears preferable. For gram-positive infections, a specific anti-gram-positive antibiotic is not needed in every patient and can safely be added upon identification of the pathogen in those patients not responding to empirical therapy.

Agranulocytosis↗
PubMed1991

High circulating levels of interleukin-6 in patients with septic shock: evolution during sepsis, prognostic value, and interplay with other cytokines. The Swiss-Dutch J5 Immunoglobulin Study Group.

PURPOSE AND PATIENTS: We measured the serum concentrations of interleukin-6 (IL-6) in 70 patients with established septic shock caused predominantly by gram-negative bacteria. The aims of the study were to determine whether and for how long IL-6 was detectable in the circulation of these patients, to assess whether IL-6 levels were associated with patients' outcomes, and, finally, to examine the interplay between IL-6, tumor necrosis factor (TNF), interleukin-1 beta (IL-1 beta), and interferon-gamma (IFN-gamma). RESULTS: IL-6 was detected in 64% of the patients at study entry but in only 18% on Day 1 and 2% on Day 10. Serum levels of IL-6 were higher (median: 3.5 ng/mL, range: less than 0.1 to 305 ng/mL) in patients dying of fulminant septic shock than in those surviving (median: 0.5 ng/mL, range: less than 0.1 to 135 ng/mL; p = 0.003) or in those with a transient reversal of shock but who ultimately died of a relapse of shock (median: less than 0.1 ng/mL, range: less than 0.1 to 12.5 ng/mL; p = 0.005). However, no cutoff values of IL-6 confidently predicted the outcome of an individual patient. The serum concentrations of IL-6 measured at study entry correlated with the duration of survival (r = -0.51, p = 0.004) and with the levels of TNF-alpha (r = 0.53; p less than 0.0001) but not with the levels of either IL-1 beta (r = 0.01, p = 0.90) or IFN-gamma (r = 0.06, p = 0.60). CONCLUSIONS: These results indicate that circulating levels of IL-6 are detectable in a majority of patients with gram-negative septic shock. Concentrations of IL-6 peaked near the onset of shock and rapidly decreased to undetectable levels within approximately 24 hours in most patients. Levels of IL-6 measured at study entry correlated with levels of TNF and with patients' outcomes. Yet, IL-6 does not appear to be a clinically useful laboratory test for predicting the outcome of an individual patient.

Adolescent↗
PubMed1991

Antibodies to lipopolysaccharides after immunization of humans with the rough mutant Escherichia coli J5.

To investigate whether immunization with Escherichia coli J5 boiled cells induces antibodies directed at deep core structures, antibodies against J5 lipopolysaccharide (LPS), Re LPS, and lipid A were measured in the serum of 70 volunteers before and 2 weeks after immunization. To improve the sensitivity and the specificity of ELISA, complexes of core LPS with high-density lipoproteins were used instead of free core LPS as antigens. A median three-fold increase in antibodies directed against J5 LPS was observed, but no significant increase in the antibodies against Re LPS or lipid A was found. Since J5 antiserum did not react with several smooth LPS or with Re LPS and lipid A, cross-reactivity could not be demonstrated. Thus, immunization of volunteers with E. coli J5 produced a modest specific antibody response against J5 LPS. The mechanism of protection previously observed with J5 antiserum remains unclear.

Antibodies, Bacterial↗
PubMed1991

Prospective randomized evaluation of ciprofloxacin versus piperacillin plus amikacin for empiric antibiotic therapy of febrile granulocytopenic cancer patients with lymphomas and solid tumors. The European Organization for Research on Treatment of Cancer International Antimicrobial Therapy Cooperative Group.

Empiric therapy for febrile granulocytopenic patients is mandatory, but whether monotherapy is a safe alternative and whether fluoroquinolones are useful agents for this indication are still controversial issues. The use of monotherapy with intravenous ciprofloxacin (200 to 300 mg every 12 h) was evaluated against combined therapy with piperacillin plus amikacin in febrile granulocytopenic patients with solid tumor or lymphoma. The study was discontinued prematurely because patients treated with ciprofloxacin had a significantly lower overall success rate than patients treated with piperacillin plus amikacin (31 of 48 patients [65%] versus 48 of 53 patients [91%], P = 0.002). Patients with gram-positive coccal bacteremia had a particularly poor outcome: therapy failed for six of eight patients (75%) treated with ciprofloxacin, while therapy failed for none of four patients treated with piperacillin plus amikacin. Death from primary infection during initially randomized protocol therapy occurred in 7 of 48 patients (14.5%) treated with ciprofloxacin and in 3 of 53 (6%) treated with piperacillin plus amikacin. This study does not support the use of this dose of intravenous ciprofloxacin as empiric monotherapy for fever in granulocytopenic patients.

Adult↗
PubMed1991

Antibiotic therapy for gram-negative bacteremia.

Although antibiotic therapy is the mainstay of therapy for gram-negative bacillary bacteremia, the amelioration of the underlying conditions, the correction of predisposing factors, the drainage of abscesses, the removal of infected foreign bodies, and adequate supportive care are also of paramount importance for curing the infection and should not be neglected. Beginning in the late 1960s, most of the clinical work on gram-negative infections has focused on the evaluation of new antibiotics. Numerous studies have shown that early, appropriate antibiotic treatment of gram-negative bacteremia significantly improved patients' outcomes and prevented the development of septic shock. Prescribing standard doses of antibiotics does not necessarily mean that therapeutic levels will be reached in all patients, and relapses of infections or breakthrough bacteremias can occur in patients with subinhibitory serum levels of antibiotics. The monitoring of serum concentrations of antibiotic is therefore recommended in critically ill septic patients. Whereas initial studies on the antibiotic treatment of gram-negative bacteremia were carried out in nonneutropenic patients, more recent clinical investigations have been performed almost exclusively in cancer patients with neutropenia. Studies conducted in the 1970s and 1980s among these patients have shown the following: (1) early empirical therapy reduced the mortality of gram-negative bacteremia; (2) therapy with a combination of two antibiotics, be it an extended spectrum penicillin plus an aminoglycoside or a third-generation cephalosporin, has significantly improved patients' outcomes; and (3) triple-drug combinations (i.e., a penicillin plus a cephalosporin plus an aminoglycoside) are not superior to combinations of beta-lactams and aminoglycosides. For the treatment of gram-negative bacteremia, clinicians today have a choice between well-established antibiotic combinations and broad-spectrum single-agent therapy with third-generation cephalosporins or carbapenem antibiotics. Although recent studies suggested that monotherapy could be as effective as combination therapy for the empirical treatment of fever in the neutropenic host, no definitive study has so far unquestionably demonstrated the equivalence of these treatments in patients with gram-negative bacteremias, especially those caused by P. aeruginosa, or in patients with adverse prognostic conditions, such as persistent and profound granulocytopenia. This literature should however be reviewed with great caution. Indeed, only a minority of studies have included a sufficient number of patients to confidently assess the impact of therapy on patients' outcomes. Obviously, small studies can have a significant risk of type II errors, that is, making false-negative conclusions.(ABSTRACT TRUNCATED AT 400 WORDS)

Aminoglycosides↗
PubMed1991

Anti-lipopolysaccharide and anti-tumor necrosis factor/cachectin antibodies for the treatment of gram-negative bacteremia and septic shock.

Endotoxin is composed of lipid A, the toxic moiety, of the core region, a conserved structure among Gram-negative bacteria, and of the O-side chains, a highly variable part responsible for the antigenic specificity. The concept of cross-protection afforded by antiserum raised against the core region of endotoxin is supported by the following data: experimentally antiserum protected against infections caused by a wide range of Gram-negative bacteria or endotoxins; in patients with Gram-negative bacteremia, survival was associated with high levels of anti-core antibodies, and mortality was reduced by the prophylactic or therapeutic use of immune serum or plasma. However, the proof that protection is afforded by cross-protective anti-core antibodies is still lacking. Furthermore, many experimental studies and clinical studies trials have shown controversial results. Ongoing experimental studies and recently completed clinical trials, using either polyclonal or monoclonal anti-core antibodies should help clarify the issues both of the clinical efficacy and of the mechanism of protection. Tumor necrosis factor/cachectin has been unequivocally shown, both in experimental animal models and in humans to be a pivotal mediator of the clinical and humoral manifestations of shock induced by endotoxin or by whole Gram-negative bacteria. In humans, TNF was been transiently detected in the blood of volunteers challenged with endotoxin, in a small proportion of patients with Gram-negative sepsis, but in the vast majority of patients with established septic shock. However, in patients the magnitude and the evolution of the blood concentration of TNF differed from that observed in animal models or in human volunteers after an acute challenge with either Gram-negative bacteria or endotoxin, probably reflecting differences in infectious stimuli. In children with meningococemia and in adults with Gram-negative septic shock, TNF was associated with the patient's outcome. Anti-TNF monoclonal antibodies are presently undergoing clinical investigation in patients with septic shock. However, one should keep in mind that TNF serves both beneficial and detrimental functions depending upon its concentration in body fluids.

Antibodies, Monoclonal↗
PubMed1990

Prognostic values of tumor necrosis factor/cachectin, interleukin-1, interferon-alpha, and interferon-gamma in the serum of patients with septic shock. Swiss-Dutch J5 Immunoglobulin Study Group.

Serum concentrations of immunoreactive tumor necrosis factor/cachectin (TNF), interleukin-1 beta (IL-1 beta), interferon-gamma (IFN gamma), and interferon-alpha (IFN alpha) were prospectively measured in 70 patients with septic shock to determine their evolution and prognostic values. In a univariate analysis, levels of TNF (P = .002) and IL-1 beta (P = .05) were associated with the patient's outcome, but not IFN alpha (P = .15) and IFN gamma (P = .26). In contrast, in a stepwise logistic regression analysis, the severity of the underlying disease (P = .01), the age of the patient (P = .02), the documentation of infection (nonbacteremic infections vs. bacteremias, P = .03), the urine output (P = .04), and the arterial pH (P = .05) contributed more significantly to prediction of patient outcome than the serum levels of TNF (P = .07). After 10 days, the median concentration of TNF was undetectable (less than 100 pg/ml) in the survivors, whereas it remained elevated (305 pg/ml, P = .002) in the nonsurvivors. Thus, in patients with septic shock due to various gram-negative bacteria, other parameters than the absolute serum concentration of immunoreactive TNF contributed significantly to the prediction of outcome.

Adolescent↗
PubMed1989

Clinical significance of Candida isolated from peritoneum in surgical patients.

Over a 2-year period, all surgical patients from whom Candida was isolated from intra-abdominal specimens were evaluated. All but 1 of the 49 evaluable patients had either a spontaneous perforation (57%) or a surgical opening of the gastrointestinal tract (41%). Candida caused infection in 19 patients (39%), of whom 7 had an intra-abdominal abscess and 12 peritonitis. In the other 30 patients (61%), there were no signs of infection and specific surgical or medical treatment was not required. Candida was more likely to cause infection when isolated in patients having surgery for acute pancreatitis than in those with either gastrointestinal perforations or other surgical conditions. The development of a clinical infection was significantly associated with a high initial or increasing amount of Candida in the semiquantitative culture. Surgery alone failed in 16 of 19 patients (84%), of whom 7 died and 9 recovered after combined antifungal and surgical treatment. The overall mortality and the mortality related to infections were significantly higher in the patients with intraabdominal candidal infections than in those without such infections.

Abscess↗
PubMed1989

[Candida fungemia].

From 1980 to 1986, 52 patients presented with an episode of fungemia due to Candida species at the Centre Hospitalier Universitaire Vaudois (representing 2% of the patients with positive blood cultures). In 51 of the 52 patients (98%) the infection was nosocomial, occurring after a median hospital stay of 24 days (range 4-250 days). Only 36 patients (69%) presented with an underlying condition (neoplasms in 18 patients, alcoholism in 7, diabetes in 6, immunosuppressive therapy in 5). In 19 patients (37%) an episode of bacteremia occurred prior to fungemia (median time 14 days, range 1-70 days). Candida albicans was the most commonly isolated species (71%). In 50 patients (96%) the episode of fungemia was associated with a significant, although nonspecific, clinical impairment. The digestive tract (38%) and N intravascular catheter (31%) were the two most common portals of entry for the fungemia. 32 patients (62%) received specific antifungal therapy consisting of amphotericin B in 29 patients (median total dose 450 mg, administered either alone or in association) or of ketoconazole in 3 patients. The global mortality was 46% and the fungemia-related mortality was 21%. Global and fungemia-related mortalities were significantly higher in patients not treated with antifungals than in those treated with them (87% versus 30%, p less than 0.001, and 47% versus 11%, p = 0.01 respectively).

Adolescent↗
PubMed1989

Plasminogen activator inhibitor 1: a new prognostic marker in septic shock.

The prognostic value of plasminogen activator inhibitor type 1 (PAI-1) in septic shock was investigated in 52 patients with septic shock. The patients had significantly elevated serum PAI-1 levels with respect to the control group (p = 0.002). In patients not having a rapidly fatal underlying disease, PAI-1 was significantly higher in patients dying within a week after onset of shock than in survivors (median PAI-1: 900 and 307 ng/ml, respectively; p = 0.001). The analysis of the distribution of PAI-1 levels permitted retrospectively to determine a threshold level of PAI-1 which had prognostic significance. Mortality was 71% in patients with serum PAI-1 above 550 ng/ml, whereas only two patients (6%) having a PAI-1 below 550 ng/ml died within a week. Thus, in patients with septic shock, PAI-1 appears to have a strong predictive value as to mortality. This early marker may help the clinician in identifying a subgroup of patients particularly at risk.

Adolescent↗
PubMed1988

Treatment of gram-negative septic shock with human IgG antibody to Escherichia coli J5: a prospective, double-blind, randomized trial.

In a randomized, double-blind, multicenter trial we compared the efficacy of a preparation of human IgG antibody to Escherichia coli J5 (J5-IVIG) with that of a standard IgG preparation (IVIG) for the treatment of gram-negative septic shock. At study entry, patients received a single intravenous dose of 200 mg/kg of body weight (maximal dose, 12 g) of either J5-IVIG or IVIG. Of the 100 patients randomized, 71 (30 receiving J5-IVIG and 41 receiving IVIG) had a documented gram-negative infection. Mortality from gram-negative septic shock was 50% (15 of 30) in J5-IVIG recipients and 49% (20 of 41) in IVIG recipients. In addition, treatment with J5-IVIG did not reduce the number of systemic complications of shock and did not delay the occurrence of death due to septic shock. Thus we conclude that J5-IVIG was not superior to IVIG in reducing mortality or in reversing gram-negative septic shock.

Adolescent↗
PubMed1988

Empiric antimicrobial therapy for febrile granulocytopenic cancer patients: lessons from four EORTC trials.

The results of the four EORTC trials conducted over the past 15 years suggest: (1) early empiric therapy with broad spectrum antibiotics directed against gram-negative bacterial bacteremia (GNBB) is a reasonable approach in febrile granulocytopenic patients (GCP); (2) the level and dynamics of the granulocyte count are extremely important in determining the outcome of bacteremia; severely and/or persistently neutropenic patients are the true tests of antibiotic efficacy and they benefit from antimicrobial synergism; (3) mortality from GNBB in GCP is not related directly to a given empiric antimicrobial regimen which may 'buy time' and allow appropriate therapeutic alterations; (4) only microbiologically documented infections and especially bacteremias are useful to compare responses to antimicrobial regimens; (5) the response rate of GNBB is clearly influenced by the susceptibility of the causative pathogen to the beta-lactam component of the empiric regimen and emergence of resistance to some antibiotics (cephalothin, carbenicillin, ticarcillin, azlocillin) has rendered some combinations less effective. The combination of an anti-Pseudomonas beta-lactam plus an aminoglycoside is recommended as the 'standard' for empiric therapy in febrile GCP; (6) gram-positive pathogens have become a common cause of bacteremia in GCP and although the response rate to empiric regimens may be marginal, the associated mortality is low. A general conclusion from these trials is that studies of the management of infection in GCP should include sufficient numbers of eligible patients to allow for evaluation of bacteremic patients at highest risk of death. The need for large collaborative studies stems directly from these considerations.

Agranulocytosis↗
PubMed1986

Immunocompromised animal models for the study of antibiotic combinations.

Studies of various models of Pseudomonas aeruginosa infections in neutropenic animals have demonstrated the superiority of the combination of beta-lactam and aminoglycoside antibiotics when compared with a single drug alone. A limited number of studies carried out in models of Klebsiella pneumoniae infections in neutropenic animals have shown similar results. The efficacy of double beta-lactam combinations for the treatment of gram-negative bacillary infections has not been studied as extensively; the few available reports did not show any benefit over a single beta-lactam treatment. Most studies of combined therapy in gram-positive infections have been performed in the experimental endocarditis model. Experiments in Staphylococcus aureus, Streptococcus viridans, and Streptococcus faecalis endocarditis have shown a clear-cut advantage for combined beta-lactam/aminoglycoside treatment over single beta-lactam therapy, as predicted by in vitro tests. The enhanced efficacy of combined beta-lactam/aminoglycoside treatment in both gram-negative bacillary and gram-positive coccal infections appears to result in most studies in increased and faster killing of the bacteria. With P. aeruginosa infections, however, experiments in neutropenic mice suggest that in addition to increased killing, the beta-lactam arm of the combined treatment prevents the emergence of the small colony variants that lead to treatment failures during therapy with aminoglycoside alone. For both gram-negative bacillary and gram-positive coccal infections, in vitro tests that demonstrated synergism for the combined antibiotics generally predicted enhanced therapeutic efficacy in vivo. Conversely, when no synergism was demonstrated in vitro, there was generally no increased efficacy of combined treatment in vivo. Animal models add a dimension to our understanding of the efficacy of antibiotics, both singly and in combination, that is not always apparent from the results of in vitro tests alone. These in vivo tests can be of value when planning clinical trials.

Agranulocytosis↗
PubMed1986

Clinical experience with Timentin in severe hospital infections.

Sixty-four severe infections in hospitalized patients were treated with intravenous Timentin. Most patients (mean age: 50.5 years, range 18-85) had serious underlying conditions such as agranulocytosis, heart failure, cancer, diabetes mellitus, chronic alcoholism or other functional or anatomical abnormalities. Forty-three episodes were bacteriologically proved, and bacteraemia was diagnosed in 18. The sites of infection were: lower respiratory tract (10), upper respiratory tract (10), soft tissues (9), urinary tract (7), bones (6), peritoneal cavity (3), meninges (1) and pelvis (1). In addition, 13 episodes of fever and four of septicaemia in patients with agranulocytosis were treated with Timentin plus amikacin. Overall, 59% of the episodes were cured, 14% improved and 17% failed to respond. In 9% of cases the efficacy of the Timentin was unassessable mainly because of concurrent administration of other antimicrobials. Failure appeared to be more frequent in soft tissue and intra-abdominal infections, in patients infected with bacteria susceptible to Timentin but resistant to ticarcillin and in patients superinfected with Timentin-resistant strains. Major side effects were haemorrhagic diathesis with platelet dysfunction (1), severe water sodium overload (1), and possibly pancreatitis (1). Other side effects were mild: catheter-related phlebitis, and abnormal but clinically insignificant laboratory test results. Timentin appears to be an effective and safe broad-spectrum combination which compares favourably with third-generation cephalosporins in the treatment of severe hospital infections. More experience is needed to decide whether the somewhat lower response rate in patients infected with ticarcillin-resistant strains is significant.

Acute Disease↗
PubMed1985

Disseminated candidiasis with extensive folliculitis in abusers of brown Iranian heroin.

Two cases of heroin abusers who developed disseminated candidiasis are reported. Cultures of skin lesions revealed Candida albicans, which on histology were shown to be located in and around hair shafts. Both patients recovered after treatment with amphotericin B combined with 5-fluorocytosine and either ketoconazole or dexamethasone. This unusual cutaneous syndrome of candidal infection associated with extensive folliculitis seems to be related to the use of a particular type of heroin, the so-called brown Iranian heroin.

Adult↗
PubMedDate not supplied

A role for the endocrine and pro-inflammatory mediator MIF in the control of insulin secretion during stress.

The systemic response to injury or infection is often accompanied by significant alterations in host metabolism and glucose homeostasis. Within the liver, these changes include a decrease in glycogenesis and an increase in gluconeogenesis, and in peripheral tissues, the development of insulin resistance and the increased utilization of glucose by non-insulin-dependent pathways. Depending on the severity and the duration of the response, both hyper- and hypoglycemia can ensue and each can become a clinically important manifestation of the systemic inflammatory response. The protein known as macrophage migration inhibitory factor (MIF) has been identified recently to play a central role in host immunity and to regulate glucocorticoid effects on the immune and inflammatory systems. MIF is released in vivo from activated immune cells as well as by the anterior pituitary gland upon stimulation of the hypothalamic-pituitary-adrenal axis. MIF also has been found to be secreted together with insulin from the pancreatic beta-cells and to act as an autocrine factor to stimulate insulin release. Since circulating MIF levels are elevated during stress or systemic inflammatory processes, this protein may play a central role in the control of insulin secretion during various disease states.

Humans↗