Febrile Episodes In Patients Research Articles

Ceftriaxone for the Treatment of Febrile Episodes in Nonneutropenic Patients with Hematooncological Disease or HIV Infection: Comparison of Outpatient and Inpatient Care

Background: Patients with hematooncological disease or HIV infection and febrile episodes are usually treated in hospital with broad-spectrum antibiotics. The aim of this observational study was to assess the feasibility of ambulatory parenteral antibiotic therapy in hematooncological or HIV-infected patients with confirmed or suspected infection. Methods: The results in an outpatient treatment group were compared with those obtained in a group initially treated in hospital. Data were gathered on 90 outpatients and 72 inpatients. The inclusion criteria were fever ≧37.5°C with an identified focus of infection, fever ≧38.0°C of suspected bacterial origin with no identified focus of infection, leukocytosis ≧9,000/µl or C-reactive protein elevation ≧10 mg/l. Results: Eighty outpatients and 69 inpatients were evaluable. Treatment in the outpatient group was begun with ceftriaxone. This led to defervescence in 87.5% of cases. The mean treatment duration was 7.1 days. Comparison of results in the outpatients with those initially hospitalized for treatment showed similar success rates. The mean hospital stay in the latter group was 12.9 days. Conclusions: Ceftriaxone represents an effective treatment for outpatient management of febrile episodes in patients with hematooncological disease or HIV infection. Outpatient treatment is more cost-effective than inpatient care.

Piperacillin/tazobactam: a pharmacoeconomic review of its use in moderate to severe bacterial infections.

Piperacillin/tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity against most Gram-positive and Gram-negative aerobic bacteria and anaerobic bacteria. Piperacillin/tazobactam is effective and well-tolerated in patients with lower respiratory tract infections (LRTI), intra-abdominal infections, skin and soft tissue infections, and febrile neutropenia. In comparative clinical trials against various other antibacterial regimens, piperacillin/tazobactam has shown higher clinical success rates, particularly in the treatment of patients with intra-abdominal infections and febrile neutropenia. Cost analyses of piperacillin/tazobactam have been variable, in part, because of differences in specific costs included. Three US cost analyses found that piperacillin/tazobactam had lower total medical costs than clindamycin plus gentamicin or imipenem/cilastatin in intra-abdominal infections, and ticarcillin/ clavulanic acid in community-acquired pneumonia. Piperacillin/tazobactam plus amikacin had lower total costs than ceftazidime plus amikacin in another cost analysis of patients with febrile neutropenic episodes modelled in nine European countries. However, piperacillin/tazobactam plus tobramycin was more costly than ceftazidime plus tobramycin in hospital-acquired pneumonia in a US cost analysis. In cost-effectiveness analyses, all studies of intra-abdominal infections, pneumonia and febrile neutropenic episodes consistently reported lower costs per unit of effectiveness versus comparators. Piperacillin/tazobactam was dominant (greater efficacy and lower costs) versus imipenem/cilastatin in intra-abdominal infections and ceftriaxone, ciprofloxacin or meropenem in pneumonia. Piperacillin/tazobactam plus amikacin was dominant over ceftazidime plus amikacin in the treatment of febrile neutropenic episodes. In a cost-effectiveness analysis of skin and soft tissue infection, piperacillin/tazobactam had lower costs per successfully treated patient than ceftriaxone or cefotaxime, but a slightly higher cost-effectiveness ratio than amoxicillin/clavulanic acid. All cost-effectiveness analyses were based on decision-analytical models. Piperacillin/tazobactam is likely to reduce overall treatment costs of moderate to severe bacterial infections by increasing initial treatment success, thereby reducing the length of hospital stay and the use of additional antibacterials. Piperacillin/tazobactam has shown clinical and economic advantages over standard antibacterial regimens in the treatment of intra-abdominal infections, LRTIs, febrile episodes in patients with neutropenia, and skin and soft tissue infections, although more complete published data are needed to confirm these results. Present data regarding clinical efficacy, bacterial resistance and costs would support the use of piperacillin/tazobactam as an empirical first-line option in moderate to severe bacterial infections.

Infección en pacientes neutropénicas sometidas a trasplante autólogo de progenitores hematopoyéticos por cáncer de mama

The extent and duration of neutropenia and the characteristics of the underlying disease are determinant factors for the prognosis of febrile syndromes. Despite the fact that traditionally the peripheral blood stem cell transplantation (PBSCT) were considered to cause high risk neutropenia, in all probability the neutropenia observed in the PBSCT in some solid tumours could be considered moderate risk. Febrile episodes in patients with these characteristics were evaluated. We prospectively analysed 132 autologus PBSCT in patients with breast cancer (1994-1999). Conditioning regime: STAMP V. Antibacterial prophylaxis: ofloxacin (400 mg/12 hrs PO). Classification of the febrile syndrome: bacteremia, microbiologically documented infection withut bacteremia, clinical infection and a fever of unknown origin. 122 patients had a fever (92%), mean age: 45 years (range: 27-61). There were 32 (26%) bacteremias, 13 (11%) microbiologically documented infections without bacteremia and 54 (44%) clinical infections. The mean number of days with a neutrophil count of <1x109/1 was 14 (range: 11-20). In the 74 patients (61%) that had a granulocyte colony stimulating factor (G-CSF), the mean number of days to reach a 0,5x109/I neutrophil count (7,6) and the average number of days in hospital (26) were significantly less. There was a main infectious point in 80 patients (65%): the most frequent being oropharynx in 33 cases (46%) and digestive in 29 cases (41%). 48 gram negative (GN) 29 gram positive (GP) bacteria were isolated (71% of the GN's were resistant to ofloxacin). Between 1997-1999 the GN/GP ratio was 2,3. There were no deaths related to the infection. Given the excellent evolution of our patients we can consider their neutropenia to be moderate or low risk, and they are a long way from the death rates caused by infections published by other types of hemopoietic transplants. The predominance of GN over the last few years and their limited sensitivity to quinolones means that their prophylactic use in these patients should be reconsidered.

Piperacillin/tazobactam: an updated review of its use in the treatment of bacterial infections.

Piperacillin/tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity encompassing most Gram-positive and Gram-negative aerobic bacteria and anaerobic bacteria, including many pathogens producing beta-lactamases. Evidence from clinical trials in adults has shown that piperacillin/tazobactam, administered in an 8:1 ratio, is an effective treatment for patients with lower respiratory tract, intra-abdominal, urinary tract, gynaecological and skin/soft tissue infections, and for fever in patients with neutropenia. Combination regimens of piperacillin/tazobactam plus an aminoglycoside are used to treat patients with severe nosocomial (hospital-acquired) infections. In clinical trials, piperacillin/tazobactam was significantly more effective than ticarcillin/clavulanic acid in terms of clinical and microbiological outcome in patients with community-acquired pneumonia. In patients with intra-abdominal infections, clinical and bacteriological response rates were significantly higher with piperacillin/tazobactam than with imipenem/cilastatin (administered at a dosage lower than is recommended in countries outside Scandinavia). Piperacillin/tazobactam in combination with amikacin was at least as effective as ceftazidime plus amikacin in the treatment of ventilator-associated pneumonia and was significantly more effective than ceftazidime plus amikacin in the empirical treatment of febrile episodes in patients with neutropenia or granulocytopenia. In other trials, the efficacy of piperacillin/tazobactam was similar to that of standard aminoglycoside-containing and other treatment regimens in patients with intra-abdominal, skin/soft tissue or gynaecological infections. Piperacillin/tazobactam is generally well tolerated. The most frequent adverse events are gastrointestinal symptoms (most commonly diarrhoea) and skin reactions. The incidence of adverse events with piperacillin/tazobactam is higher when the combination is given in combination with an aminoglycoside than when given as monotherapy. Because of the broad spectrum of antibacterial activity provided by piperacillin/tazobactam, it is useful for the treatment of patients with polymicrobial infections caused by aerobic or anaerobic beta-lactamase-producing bacteria. Piperacillin/tazobactam appears to have a particularly useful role in the treatment of patients with intra-abdominal infections and, in combination with amikacin, in the treatment of patients with febrile neutropenia, especially given the current prevalence of Gram-positive infections in this group.

Severe Tuberculous Meningoencephalitis in a 30-Year Old Woman with Active Systemic Lupus Erythematosus

Tuberculosis is a significant cause of morbidity and mortality in immunocompromising diseases such as systemic lupus erythematosus (SLE). It often is difficult to distinguish between central nervous system (CNS) involvement and infectious complications in SLE. We report the case of a 30-year-old woman with active SLE and severe tuberculous meningoencephalitis. The diagnosis of tuberculous meningoencephalitis was confirmed by cerebrospinal fluid culture examination, which revealed mycobacterium tuberculosis and typical findings for tuberculous meningoencephalitis on magnetic resonance imaging. Despite treatment with isoniazid, rifampicin, ethambutol, streptomycin, and prednisone, the patient developed significant neurological deficits. This case is a reminder that febrile episodes in patients with SLE should always lead to aggressive evaluation for infection. The early clinical symptoms of tuberculous meningitis often are nonspecific. Because of the unfavorable prognosis in latetreated and untreated cases, even a suspicion should lead to a trial of antituberculous treatment.

Antibiotic treatment of febrile episodes in neutropenic cancer patients. Clinical and economic considerations.

The increased frequency of infections caused by Gram-positive microorganisms, and the expansion of resistant pathogens resulting from institutional therapeutic practices, represent some of the emerging issues of empirical drug treatment of cancer patients with febrile neutropenia. However, the therapeutic strategies for the treatment of these patients have progressed remarkably over the last decade. Individual therapy in the light of the principal clinical features (in particular, the degree and estimated duration of neutropenia, as well the presence of other potential factors favouring infection such as long-standing intravascular catheters) and local microbial ecology have emerged as the leading concepts. Empirical drug monotherapy has been recognised as a feasible alternative to combination therapy, at least in selected low-risk patients. The indiscriminate use of empirical glycopeptides should be discouraged to prevent the emergence of resistant bacteria, especially in centres where methicillin-resistant staphylococci have not yet become a major issue. Empirical antifungal therapy with amphotericin B is still essential for a successful outcome in case of fever persistence or recurrence. Finally, selected febrile neutropenic patients who exhibit a better prognosis can be handled on an outpatient basis. The prophylactic use of haemopoietic growth factors has been shown to augment cost savings substantially in the management of neutropenic patients via a reduction in the duration and severity of the neutropenia, as well as infectious complications. Although data from economic analyses are not yet available, some cost-containment strategies such as outpatient treatment, monotherapy, and use of more convenient antibiotic combinations may lead to a reduction of therapy expenditures for febrile episodes in these patients.

Management of catheter-related bacteremia and fungemia in patients on total parenteral nutrition

To diminish the risk of serious complications from catheter-related bacteremias or fungemias, an optimized diagnosis andantimicrobial therapy is essential and early catheter removal should be considered. Prompt removal of the catheter and targeted antimicrobial treatment remains a common approach for febrile episodes in patients on total parenteral nutrition. However, novel tools allow diagnosis of catheter-related infections with the catheter in situ. Moreover, many of the established catheter-related infections caused by coagulase-negative staphylococci can successfully be treated with the catheter still in place. The use of these advanced management options depends widely on the resource of the microbiology laboratory as well as the type of catheter and severity of the patient's disease.

Nature and outcome of febrile episodes in patients with pancreatic and hepatobiliary cancer

Fifty febrile episodes in patients with hepatobiliary and pancreatic cancer were reviewed. Biliary obstruction often resulting in cholangitis was an important predisposing factor, whereas neutropenia (< 500 PMN/mm3) was uncommon (10%). Microbiologically documented infections originating from the gastrointestinal tract were predominant, with Enterococcus faecalis and Escherichia coli being isolated most often. Non-infectious causes of fever occurred in 16% of patients. Only one patient developed a fungal infection. The overall response rate to therapy was 94%, with 32% being eligible for outpatient management. These data are quite different from those generated from patients with hematologic malignancies and indicate that disease-site specific management guidelines need to be developed for febrile episodes in patients with various underlying neoplasms.

Current Concepts in the Treatment of Genitourinary Tract Disorders in the Older Individual

Genitourinary problems, including neurogenic dysfunction, impotence, prostatism, urinary tract infections, and prostate cancer, are common in the elderly, and most of the symptoms can be alleviated through pharmacological management. Patients with neurogenic dysfunction who present with symptoms such as incontinence and urinary retention can be appropriately managed with bladder and sphincter relaxants or stimulants. Anticholinergic agents in the form of oxybutynin, flavoxate, and propantheline are effective bladder relaxants, and phenoxybenzamine, prazosin, and terazosin are commonly used as sphincter relaxants. Bethanechol chloride is the agent most commonly used to stimulate bladder contraction, but physicians should be careful when prescribing it for elderly patients with cardiovascular problems. Organic and psychogenic causes of impotence usually overlap, and oral agents have limited use in the treatment process. The use of yohimbine has increased recently, but its value and rate of success remains questionable. Testosterone is being used widely to treat impotence, but it is only helpful to patients with hypogonadism and should be used with discretion in the elderly, who have a high incidence of prostate cancer. Vasoactive intracavernous pharmacotherapy, on the other hand, is a recently discovered alternative to testosterone with promising results. Although the treatment of choice for benign prostatic hypertrophy is surgery, there have been important pharmacological advances in treating this disorder. alpha-Adrenergic antagonists and anti-androgenic agents have been found to relieve the symptoms of prostatic enlargement. The use of chemotherapeutic and antibiotic agents to treat and suppress acute and chronic urinary tract infections is reviewed; these are second only to pulmonary infections as the most frequent cause of febrile episodes in patients over the age of 65. Lower urinary tract infections can be treated with almost any antibacterial agent. Upper urinary tract infections require full genitourinary evaluation and appropriate antibiotics should be used according to the urine culture sensitivity studies. With the advent of new hormonal agents, more choices are now available for the management of prostate cancer, which is the second most common malignancy in men. Diethylstilbestrol (stilboestrol), an oral estrogen, remains a commonly used agent to achieve castrate levels of androgens in advanced prostatic carcinoma. Agonist analogues, such as goserelin and leuprorelin, of gonadotrophin-releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH); or gonadorelin] achieve the same results as diethylstilbestrol but without the cardiovascular side effects. Antiandrogens are also being used in combination with GnRH agonists to produce complete androgen blockage, with mixed results.

Acute Oral Candidiasis during Febrile Episodes in Immunocompromised Patients with Haematologic Malignancies

To estimate clinical, pathogenic and serological aspects of acute oral candidiasis (AOC) during febril episodes in patients with haematologic malignancies, 23 consecutive patients who developed AOC within 7 days from start of fever were compared with 23 consecutive patients who did not develop AOC. The duration of fever and severe granulocytopenia (less than 0.5 x 10(9)/l) was significantly longer in patients with AOC than in patients without AOC, the median differences between the patients with and without AOC being 4 and 3 days, respectively. Development of AOC could not be correlated to a change in the qualitative composition of the oral microflora. The thrombocyte count was lower in patients with AOC on day 4, whereas no differences were found in leukocyte counts. The prevalences of Candida albicans agglutinin titres greater than or equal to 5 were similar in patients with (24%) and without AOC (33%), and in controls (29%). Seroconversion or a significant increase in the agglutinin titre occurred in 4 patients with AOC and long-lasting fever, who became afebrile after systemic antifungal therapy. It is concluded that AOC is associated with long-lasting fever and decreased bone marrow function as judged by low thrombocyte counts, but not related to specific bacteria in the oral cavity or to an increased occurrence of C. albicans antibodies in the serum.

Combination Therapy With Ticarcillin and Sulfamethoxazole-Trimethoprim for Infections in Patients With Cancer

Intravenous (IV) antibiotic therapy with a combination of ticarcillin disodium and sulfamethoxazole-trimethoprim was administered as initial empiric treatment of 218 febrile episodes in patients with cancer. Seventy-nine (77%) of 102 episodes of infection were cured, and the temperature returned to normal in 88 (74%) of 199 febrile episodes without proved infection. The response rates for the major sites of infection were as follows: septicemia, 89%; pneumonia, 52%, soft-tissue infections, 85%; and urinary tract infections, 100%. The cure rate of Gram-negative aerobic bacillary infections was 87%. No significant influence of initial neutrophil count on response rate was noted, although patients in whom the neutrophil count increased during therapy had a higher response rate (84%) than patients in whom the neutrophil count decreased or remained stable (72%). The combination of ticarcillin and IV sulfamethoxazole-trimethoprim is satisfactory initial empiric antibiotic therapy for febrile episodes in neutropenic patients with cancer.

Granulocyte Transfusion Therapy

The effect of granulocyte transfusions on the course of infection in patients under treatment for acute leukemia was evaluated by comparing 19 febrile episodes in 15 patients receiving antibiotics alone with 18 febrile episodes in 13 patients receiving antibiotics in combination with granulocyte transfusions from ABO-matched donors. Both groups had a similar age, sex distribution and duration of disease prior to the febrile episode. About two-thirds of the patients in both groups had acute myeloblastic leukemia. 94% of the patients in the transfused group and 74% of the control group survived the febrile episode. In patients with positive blood cultures all transfused patients survived as compared to only 57% in the control group (p=0.05). In patients with persistent bone marrow failure 92% of the transfused patients survived as compared to 73% in the control group. Granulocyte transfusions had no effect on the outcome of febrile episodes in patients with negative blood cultures or early recovery of marrow function. These data appear to support the contention that granulocyte transfusions are beneficial in patients with blood culture-proved sepsis with persistent neutropenia.

Bacteriological Contamination of Dialyzers

Membranes from Gambro Lundia Nova dialyzers were investigated for presence of bacteria after hemodialysis with centrally and peripherally mixed dialysate. Centrally mixed dialysate was found contaminated with Pseudomonas aeruginosa, and bacterial cultures as well as electron scanning micrographs showed the presence of these bacteria on the dialysate side as well as on the blood side of membranes from dialyzers perfused with this dialysate during hemodialysis. No bacteria were found on membranes used with peripherally mixed dialysate, in which very few bacteria were found. Despite this the frequency of febrile episodes in patients submitted to hemodialysis with the two different dialysate mixing systems showed no significant difference in our material.

Neutropenia, Fever, and Infection in Children With Acute Lymphocytic Leukemia

In an attempt to determine the relationship between neutropenia (absolute granulocyte count less than 1,000/cu mm), infection, and disease status, 20 patients with acute lymphoblastic leukemia were observed for a total of 34 patient-years. Febrile episodes occurred with much greater frequency in patients during the course of treatment induction (0.9/mo), or while in relapse (2.46/mo) than while in remission (0.19/mo). A cause for fever was identified much more frequently in patients in remission, both when neutropenic and nonneutropenic. When absolute granulocyte counts fell below 200/cu mm, a cause for fever was generally identified regardless of disease status. We propose that the majority of febrile episodes in patients at the time of induction of treatment or in relapse with neutrophil counts of more than 200/cu mm are caused by the disease process rather than secondary to a diagnosable infection.