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      Tratamento de pneumonia em pacientes hospitalizados 3/4 resultado de um estudo clínico multicêntrico utilizando uma cefalosporina de quarta geração (cefepima) Translated title: Treatment of nosocomial pneumonia: a prospective and multicenter study used cefepime

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          Abstract

          OBJETIVO: Avaliar a eficácia e a segurança da cefepima no tratamento de pneumonia grave em pacientes hospitalizados. CASUÍSTICA E MÉTODOS: Realizamos um estudo perspectivo, multicêntrico, não comparativo envolvendo 148 pacientes (62 com pneumonia hospitalar, 34 com pneumonia comunitária e 52 formas indefinidas). A cefepima foi administrada por via intravenosa (1.000 a 2.000mg cada 12 horas), sendo que as doses também foram ajustadas para a função renal. A resposta clínica foi avaliada 48 horas após o término da terapêutica com cefepima. RESULTADOS: A média de idade foi de 56,4 ± 20,31 anos. As bactérias mais comuns isoladas nos pacientes com pneumonia hospitalar foram: 5 Pseudomonas aeruginosa (8,06%); 7 Pseudomonas sp. (11,29%); 6 Klebsiella sp. (9,68%); 3 E. coli (4,84%); 2 Acinetobacter baumannii (3,23%); 3 Staphylococcus aureus (4,84%); 3 Streptococcus pneumoniae (4,84%); 5 outras (8,06%). Os mais comuns isolados nos pacientes com pneumonia adquirida na comunidade foram: 2 Streptococcus pneumoniae (5,88%); 1 S. aureus (2,94%); 2 P. aeruginosa (5,88%) e 2 K. pneumoniae (5,88%). A eficácia clínica foi observada em 137/148 dos casos (92,56%) sendo que a resolução parcial foi obtida em 20,27% e cura em 72,29%. Falha de tratamento foi encontrado em 10 pacientes (6,75%) e um caso não foi avaliado. Eventos adversos foram observados em 5/148 pacientes (3,38%). CONCLUSÃO: Nosso estudo sugere que a cefepima é seguro e efetivo no tratamento de pneumonia grave em pacientes hospitalizados.

          Translated abstract

          OBJECTIVE: To evaluate efficacy and safety of cefepime in severe pneumonia of hospitalized patients. DESIGN AND PATIENTS: A prospective, multicenter, open trial was performed with 148 patients (62 patients with nosocomial pneumonia; 34 with community-acquired pneumonia and 52 undefined forms). Cefepime was intravenously administered (1,000 to 2,000mg every 12 hours), and doses were adjusted for renal function. The efficacy endpoint was clinical response at 48 hours after completion of therapy. RESULTS: The mean age was 56.4 ± 20,31 years. The most common bacterias isolated from patients with nosocomial pneumonia were: 5 (8.06%) Pseudomonas aeruginosa; 7 (11.29%) Pseudomonas sp.; 6 (9.68%) Klebsiella sp.; 3 (4.84%) E.coli; 2 (3.23%) Acinetobacter baumannii; 3 (4.84%) Staphylococcus aureus; 3 (4.84%) Streptococcus pneumoniae; 5 (8.06%) others. The most common isolates from patients with community-acquired pneumonia were: 2 (5.88%) Streptococcus pneumoniae; 1 (2.94%) S. aureus; 2 (5.88%) P. aeruginosa and 2 (5.88%) K. pneumoniae. Clinical efficacy was demonstrated in 137/148 (92.56%) of the cases since improvement was obtained in 20.27% and healing in 72.29%. Failure of the treatment was observed in 10 patients (6.75%) and one patient the evaluation was not possible. Adverse events were reported for 5/148 patients (3.38%). CONCLUSION: Our data suggest that cefepime was safe and effective for treatment of severe pneumonia in hospitalized patients.

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          Severe community-acquired pneumonia. Epidemiology and prognostic factors.

          Over a period of 4 consecutive yr, 92 nonimmunosuppressed patients (21 women and 71 men aged 53 +/- 16 yr, means = SD) with critical acute respiratory failure (PaO2/FiO2, 209 +/- 9 mm Hg) caused by severe community-acquired pneumonia were admitted to the respiratory intensive care unit (RICU) of a general hospital. The most frequent underlying clinical condition was chronic obstructive pulmonary disease (44 patients, 48%). A total of 56 patients (61%) required mechanical ventilation for a mean period of 10.7 +/- 12.5 days, 29 of them (52%) needing PEEP (9.9 +/- 3.8 cm H2O). A group of 23 (25%) patients had criteria of adult respiratory distress syndrome (ARDS). A causal microorganism was identified in 48 patients (52%), the two most frequent etiologies being Streptococcus pneumoniae (14, 15%) and Legionella pneumophila (13, 14%). Pseudomonas aeruginosa (5, 5%) was always associated with bronchiectasis. Mortality due to severe community-acquired pneumonia was 22% (20 patients). According to univariate analysis, mortality was associated with anticipated death within 4 to 5 yr, inadequate antibiotic treatment before RICU admission, mechanical ventilation requirements, use of PEEP, FIO2 greater than 0.6, coexistence of ARDS, radiographic spread of the pneumonia during RICU admission, septic shock, bacteremia, and P. aeruginosa as the cause of the pneumonia. Further, recursive partitioning analysis selected two factors significantly related to the prognosis: the radiographic spread of the pneumonia during RICU admission and the presence of septic shock.(ABSTRACT TRUNCATED AT 250 WORDS)
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            In vivo selection of porin-deficient mutants of Klebsiella pneumoniae with increased resistance to cefoxitin and expanded-spectrum-cephalosporins.

            Four Klebsiella pneumoniae isolates (LB1, LB2, LB3, and LB4) with increased antimicrobial resistance were obtained from the same patient. The four isolates were indistinguishable in biotype, plasmid content, lipopolysaccharide, and DNA analysis by pulse-field gel electrophoresis. Isolate LB1 made TEM-1 and SHV-1 beta-lactamases. Isolates LB2, LB3, and LB4 produced SHV-5 in addition to TEM-1 and SHV-1. MICs of cefoxitin, ceftazidime, and cefotaxime against LB1 were 4, 1, and 0.06 micrograms/ml, respectively. MICs of ceftazidime against K. pneumoniae LB2, LB3, and LB4 were > 256 micrograms/ml, and those of cefotaxime were 2, 4, and 64 micrograms/ml, respectively. MICs of cefoxitin against K. pneumoniae LB2 and LB3 were 4 micrograms/ml, but that against K. pneumoniae LB4 was 128 micrgrams/ml. K. pneumoniae LB4 could transfer resistance to ceftazidime and cefotaxime, but not that to cefoxitin, to Escherichia coli. Isolate LB4 and cefoxitin-resistant laboratory mutants lacked an outer membrane protein of about 35 kDa whose molecular mass, mode of isolation, resistance to proteases, and reaction with a porin-specific antiserum suggested that it was a porin. MICs of cefoxitin and cefotaxime reverted to 4 and 2 micrograms/ml, respectively, when isolate LB4 was transformed with a gene coding for the K. pneumoniae porin OmpK36. We conclude that the increased resistance to cefoxitin and expanded-spectrum cephalosporins of isolate LB4 was due to loss of a porin channel for antibiotic uptake.
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              Cefepime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

              Cefepime is a 'fourth' generation cephalosporin that has a broader spectrum of antibacterial activity than the third generation cephalosporins and is more active in vitro against Gram-positive aerobic bacteria. The fact that cefepime is stable to hydrolysis by many of the common plasmid- and chromosomally-mediated beta-lactamases, and that it is a poor inducer of type I beta-lactamases, indicates that cefepime may be useful for treatment of infections resistant to earlier cephalosporins. In comparative trials, cefepime 1 to 2 g, usually administered intravenously twice daily, was as effective as ceftazidime 1 to 2 g, usually administered 3 times daily, for treatment of bacteraemia and infections of the lower respiratory tract, urinary tract, pelvis and skin and skin structures. Furthermore, cefepime was as effective as ceftazidime and piperacillin or mezlocillin in combination with gentamicin when administered as empirical treatment for fever in patients with neutropenia. A limited number of trials have found cefepime to be as effective as cefotaxime for the treatment of gynaecological and lower respiratory tract infections. Similarly, cefepime 2 g twice daily intravenously (alone or in combination with metronidazole) was as effective as gentamicin in combination with mezlocillin or clindamycin, respectively, for the treatment of intra-abdominal infection. Cefepime has a linear pharmacokinetic profile, an elimination half-life of approximately 2 hours and is primarily excreted by renal mechanisms as unchanged drug. Cefepime has a tolerability profile similar to that of other parenteral cephalosporins; adverse events are primarily gastrointestinal in nature. A total of 1.4 and 2.9% of patients receiving cefepime 2 g/day, respectively, required treatment withdrawal as a result of any adverse event. Thus, cefepime has the advantage of an improved spectrum of antibacterial activity, and is less susceptible to hydrolysis by some beta-lactamases, compared with third generation cephalosporins. Despite these advantages, cefepime has not been found to be more effective than ceftazidime and cefotaxime in clinical trials, although most trials selected patients with organisms sensitive in vitro to both comparator agents. Further trials, particularly in areas of widespread bacterial resistance, are required to confirm the positioning of cefepime for treatment of serious infection, and in particular to further explore whether its potential advantages result in clinical benefits.
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                Author and article information

                Journal
                ramb
                Revista da Associação Médica Brasileira
                Rev. Assoc. Med. Bras.
                Associação Médica Brasileira (São Paulo, SP, Brazil )
                0104-4230
                1806-9282
                March 1999
                : 45
                : 1
                : 02-08
                Affiliations
                [01] orgnameUniversidade Federal de São Paulo orgdiv1Hospital das Clínicas orgdiv2Divisão de Moléstias Infecciosas
                [02] São Paulo SP orgnameUniversidade de São Paulo orgdiv1Faculdade de Medicina
                Article
                S0104-42301999000100002 S0104-4230(99)04500102
                957aa2ae-d262-407b-9372-f9d5d1256845

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

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                SciELO Brazil

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                Categories
                Artigos Originais

                Community acquired pneumonia,Nosocomial pneumonia,Cephalosporin,Cefepime,Pneumonia adquirida na comunidade,Pneumonia nosocomial,Cefalosporina,Cefepima

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