Urinary tract infections caused by multi-drug resistant Proteus mirabilis: Risk factors and clinical outcomes.

BACKGROUND: Proteus mirabilis (PM) as well as other members of the Enterobacteriaceae family are a leading cause of infectious diseases in both the community and acute care settings. The prevalence of multi-drug resistant (MDR) bacterial isolates have increased in the last few years, affecting the prognosis and survival of hospitalized patients. The aim of our study was to determine the risk factors and clinical outcomes of urinary tract infections (UTIs) caused by MDR PM in patients hospitalized in our institution. METHODS: This was a retrospective matched case-control study. Records of patients with PM-positive urine culture were reviewed, and data were included for analysis. RESULTS: Univariate analysis revealed that the variables significantly associated with acquisition of MDR PM vs non-MDR PM UTI were younger age ([in years] median 77.5, range 20-94 vs median 78, range 40-94, p = 0.04), other concomitant infectious diseases (57.1 vs 35.7%, p = 0.037),number of prior infectious diseases (mean 0.95 +/- 0.99 vs 0.57 +/- 0.85, p = 0.035), diagnosis of infection at hospital admission (67.9 vs 42.9%, p = 0.008), and prior therapy with antipseudomonal penicillin (17.9 vs 1.8%, p = 0.004),respectively. Mean length of hospitalization was 29.95 days for the MDR group and 30.04 days for the non-MDR group(p = non-significant [NS]). The crude mortality rate following hospital admission was 19/56 (33.9%) vs 14 (25%)in the MDR PM and non-MDR PM groups, respectively(p = 0.300, odds ratio [OR] 1.54, 95% confidence interval[CI] 0.63-3.82). The production of extended-spectrum beta lactamases(ESBL) was found in 100% of MDR-PM vs 31.5%of non-MDR-PM urine isolates (p < 0.001). All variables found to be significantly associated with MDR-PM UTI were included in a logistic regression model. Independent risk factors for MDR-PM UTI were empiric cephalosporin therapy(OR 4.694, 95% CI 1.76-12.516, p = 0.002) and prior antipseudomonal penicillin (piperacillin/tazobactam) therapy during the last year (OR 11.175, 95% CI 1.09-114.2,p = 0.04). CONCLUSIONS: Prior piperacillin/tazobactam and empiric cephalosporin use were the independent risk factors of MDR-PM strains. All MDR-PM urinary isolates at our institution were ESBL producers. Therefore, carbapenem use remains the only available treatment option for MDR-PM isolates in our institution.

Impact of 4% chlorhexidine whole-body washing on multidrug-resistant Acinetobacter baumannii skin colonisation among patients in a medical intensive care unit.

The prevalence of skin colonisation with Acinetobacter baumannii (ACBA) on admission to the medical intensive care unit (MICU) was studied in an institution endemic for ACBA bloodstream infections (BSIs). The impact of 4% chlorhexidine gluconate (4% CG) whole-body washing on the patients' ACBA skin colonisation was also determined. A prospective cohort trial in a MICU during March 2002 to December 2003 was performed, with a comparison between the prevalence and incidence of ACBA-BSIs obtained after intervention and retrospectively. During the intervention period, ACBA skin-screening swabs were taken from all patients on admission and periodically until discharge. Patients underwent whole-body disinfection with 4% CG immediately after obtaining the initial cultures. Disinfection was carried out on a daily basis until discharge, regardless of colonisation status. Of the 320 patients at ward admission, 55 (17%) yielded ACBA. The prevalence of ACBA colonisation among the remaining MICU patients was 5.5% at 24h and 1% at 48h following the disinfection regimen (P=0.002, OR: 2.4). Following a second screen, 80% of colonised patients were decolonised. Prevalence of ACBA-BSIs decreased from 4.6 to 0.6 per 100 patients (P < or = 0.001; OR: 7.6) and incidence decreased from 7.8 to 1.25 (85% reduction). We conclude that daily whole-body disinfection with 4% CG significantly reduced ACBA skin colonisation. This regimen may be considered in addition to well-known infection control measures, particularly in institutions with endemic rates of multidrug-resistant ACBA-BSIs.

Regional community-acquired urinary tract infections in Israel: diagnosis, pathogens, and antibiotic guidelines adherence: a prospective study.

INTRODUCTION: The identification and treatment of hospitalized patients with community-acquired urinary tract infections (CAUTI) may be a challenge. The pathogens causing the infection and their relative proportions vary geographically and with time. This observational prospective study had three primary goals: (1) to estimate the likelihood of diagnosis of CAUTI upon admission; (2) to evaluate adherence to the institutional recommendations; (3) to assess the compatibility of the current local antibiotic recommendations with a pathogen's distribution and with its drug sensitivities. METHODS AND RESULTS: Two hundred and twenty-three patients with positive urinary cultures fulfilling criteria for CAUTI were studied. Only 54 (24.2%) were diagnosed as having a urinary tract infection upon admission. Approximately 90% of the patients, who were correctly diagnosed, received the institutional recommended antibiotic therapy (ofloxacin or cefuroxime). Gram-negative intestinal flora comprised 86.1% (192 patients) of the causative microorganisms. Of these, 20.3% of the pathogens demonstrated resistance to ofloxacin and 19.8% to cefuroxime. The prevalence of Escherichia coli, the most common pathogen of UTI, significantly declined in the current study, from 70.5% in 1991 to 56% in 2000. CONCLUSIONS: We observed a low sensitivity in diagnosing community-acquired urinary tract infections upon admission. In patients correctly diagnosed, the use of recommended antibiotics was high. A substantial percentage of the pathogens were resistant to the recommended antibiotics. This study stresses the need for frequent re-evaluation of the prevalence of pathogens involved in regional community-acquired urinary tract infections and the adjustment of the empirical first-line treatment accordingly.

Characteristics of low-risk patients hospitalized with community-acquired pneumonia.

BACKGROUND: Despite the wide distribution of different severity scoring systems for community-acquired pneumonia (CAP) patients, low-risk patients are frequently hospitalized, contrary to current recommendations. The aim of our study was to determine the rate, clinical characteristics, and outcome of low-risk patients with CAP admitted to our institution. METHODS: During an 18-month period, we prospectively screened all patients admitted to the Division of Internal Medicine with a presumptive diagnosis of CAP. Pneumonia Outcome Research Team (PORT) score and pneumonia severity index (PSI) were calculated for all patients during the first 24 h. RESULTS: A total of 591 patients had a diagnosis of CAP. Some 196 patients (33.1%) were low-risk (PSI class I, II), 98 (16.6%) intermediate (PSI III), and 297 (50.3%) high-risk patients (PSI IV, V). Patients in low-risk classes were younger (45.5+/-15.8 vs. 65.0+/-12.5 and 74.9+/-11.8 years, respectively, p<0.001) and had fewer background diseases. They had shorter hospitalizations than intermediate- and high-risk groups (4.4+/-3.2, 5.3+/-3.4, and 6.8+/-6.4 days, respectively, p<0.001). There was a significant difference in 30-day mortality between the different risk groups: 0% in the low-risk, 2.0% in the intermediate-risk, and 9.4% in the high-risk group (p<0.001). CONCLUSION: The considerable proportion of low-risk patients hospitalized due to CAP was found to be comparable to the stable 30% rate reported in the literature. We conclude that physicians tend to opt for a wide safety range when considering a CAP patient hospitalization, rather than make a decision based only on severity score calculation.

Reduction of blood culture contamination rate by an educational intervention.

The efficacy of an educational intervention to prevent blood culture contamination (BCC) in internal medicine was studied in two medical wards in a busy tertiary-care hospital in which blood cultures were obtained by physicians rather than dedicated phlebotomists. Baseline BCC rates were 5.7% and 7.1% in intervention and control wards, respectively (p 0.6), compared with 1.95% and 6.7%, respectively, post-intervention (p < 0.001). Following multivariate analysis, only an absence of intervention was an independent variable associated with BCC. Thus simple educational intervention reduced BCC in internal medicine and was considered to be cost-effective.

Elevated NADPH-oxidase activity in neutrophils from bile-duct-ligated rats: changes in the kinetic parameters and in the oxidase cytosolic factor p47.

Stimulated superoxide generation was 2-fold higher in neutrophils from 20 rats with common bile-duct ligation (CBDL) compared to that of 20 sham-operated control rats. In order to study the mechanism of the higher NADPH oxidase activity in CBDL rats, the kinetic parameters of NADPH oxidase were analyzed. The Vmax of the NADPH oxidase in CBDL rat neutrophils was significantly higher than that of control rat neutrophils (10.2 and 5.3 nmol/min, respectively). The membrane and cytosol fractions of the oxidase were studied in a cell-free system. Neutrophil cytosol from CBDL rats added to neutrophil membranes from either CBDL or control rats produced 22.4 +/- 1.6 and 21.0 +/- 1.4 nmol/10(6) cells per 10 min, respectively. When neutrophil cytosol from control rats was mixed with neutrophil membranes from control or CBDL rats the generation of superoxide was 10.6 +/- 1.4 and 10.0 +/- 1.5 nmol/10(6) cells per 10 min, respectively. These results suggest that the cytosol components of the oxidase regulate its activity. By immunoblot analysis it was shown that the amount of the cytosolic factor p47 in neutrophils of CBDL rats is higher than that present in an equal number of neutrophils from control rats.

Drug-resistant HIV infection among drug-naive patients in Israel.

BACKGROUND: In Israel, <0.06% of the general population is infected with human immunodeficiency virus (HIV), with a much higher prevalence among specific groups. These groups are distinguished demographically by risk behavior category and by virus subtype. We investigated transmission of drug resistance within groups to assess the impact of these factors. METHODS: Plasma samples from >15% of all patients with new diagnoses of HIV infection were randomly collected between June 1999 and June 2003. Sequences from 176 drug-naive patients included 20 of subtype A, 20 of subtype AE, 2 of subtype AC, 29 of subtype B, 100 of subtype C, and 5 of subtype F. RESULTS: Major drug resistance mutations (protease: L90M; reverse transcriptase: M41L, K103N, V106M, M184V, Y181S, G190A, L210W, T215Y/F, and K219R) were detected in 1 subject with A subtype, 3 with subtype B, and 9 with subtype C. In addition, 1 subject with A subtypes, 2 with subtype B, and 10 with subtype C had secondary mutations (protease: M46I; reverse transcriptase: A98G, K101Q, and V108I). Only 1 patient had mutations associated with >1 class of drugs. Among subjects who contracted HIV infection in Israel, 16 of 56 (1 of 7 with subtypes A or AE, 4 of 17 with subtype B, and 11 of 32 with subtype C; P=.7-1.0) carried resistant virus--a significantly higher proportion (P<.001) than in subjects infected in other countries (10 of 120 infected). CONCLUSIONS: Drug-resistant virus was detected in 14.8% of patients with new diagnoses of HIV infection but in 28.6% of patients known to have been infected in Israel. The implications include a need for pretreatment resistance testing and for better programs aimed at prevention of transmission, directed particularly at patients. We did not find significant differences in transmission of resistant virus between those infected with subtypes B and C, despite the different demographic background. A conclusive analysis and interpretation should await a more extensive study.

The HIV protease inhibitor nelfinavir induces insulin resistance and increases basal lipolysis in 3T3-L1 adipocytes.

HIV protease inhibitors (HPIs) are potent antiretroviral agents clinically used in the management of HIV infection. Recently, HPI therapy has been linked to the development of a metabolic syndrome in which adipocyte insulin resistance appears to play a major role. In this study, we assessed the effect of nelfinavir on glucose uptake and lipolysis in differentiated 3T3-L1 adipocytes. An 18-h exposure to nelfinavir resulted in an impaired insulin-stimulated glucose uptake and activation of basal lipolysis. Impaired insulin stimulation of glucose up take occurred at nelfinavir concentrations >10 micromol/l (EC(50) = 20 micromol/l) and could be attributed to impaired GLUT4 translocation. Basal glycerol and free fatty acid (FFA) release were significantly enhanced with as low as 5 micromol/l nelfinavir, displaying fivefold stimulation of FFA release at 10 micromol/l. Yet, the antilipolytic action of insulin was preserved at this concentration. Potential underlying mechanisms for these metabolic effects included both impaired insulin stimulation of protein kinase B Ser 473 phosphorylation with preserved insulin receptor substrate tyrosine phosphorylation and decreased expression of the lipolysis regulator perilipin. Troglitazone pre- and cotreatment with nelfinavir partly protected the cells from the increase in basal lipolysis, but it had no effect on the impairment in insulin-stimulated glucose uptake induced by this HPI. This study demonstrates that nelfinavir induces insulin resistance and activates basal lipolysis in differentiated 3T3-L1 adipocytes, providing potential cellular mechanisms that may contribute to altered adipocyte metabolism in treated HIV patients.

Surveillance of chronic haemodialysis-associated infections in southern Israel.

During a 12-month surveillance period, haemodialysis (HD) patients in southern Israel were categorised according to the type of vascular access site (VAS), i.e., arteriovenous (AV) fistula, synthetic AV graft, and cuffed or non-cuffed vascular catheters. Endpoints, expressed as cases/100 patient-months, were: incidence of hospital admission; antibiotic therapy; bloodstream infection (BSI); and VAS infection. These were compared to Centers for Disease Control (CDC) surveillance data, overall and by VAS type. In total, 2568 patient-months were analysed. The VAS distribution differed significantly from CDC data for fistulas (72% vs. 31%), grafts (12% vs. 41%), cuffed catheters (11% vs. 25%) and non-cuffed catheters (5% vs. 3%) (p < 0.0001 in all cases). Of 151 admissions, 32% resulted from infection, for which 112 antibiotic courses (22% vancomycin) were given. There were 16 BSIs, three involving resistant strains. The incidences of admission, antibiotic therapy, BSI and VAS infection were significantly lower overall, compared to CDC rates, as were most VAS-specific endpoints. These differences may be explained by VAS type distribution, although other factors may also be involved. Reporting regional or national surveillance data may allow a standardised comparison of the incidence of HD-associated infections.

Cytosolic phospholipase A2 is responsible for prostaglandin E2 and leukotriene B4 formation in phagocyte-like PLB-985 cells: studies of differentiated cPLA2-deficient PLB-985 cells.

Our previously established model of cytosolic phospholipase A(2) (cPLA(2))-deficient, differentiated PLB-985 cells (PLB-D cells) was used to determine the physiological role of cPLA(2) in eicosanoid production. Parent PLB-985 (PLB) cells and PLB-D cells were differentiated toward the monocyte or granulocyte lineages using 5 x 10(-)(8) M 1,25 dihydroxyvitamin D(3) or 1.25% dimethyl sulfoxide, respectively. Parent monocyte- or granulocyte-like PLB cells released prostaglandin E(2) (PGE(2)) when stimulated by ionomycin, A23187, opsonized zymosan, phorbol 12-myristate 13-acetate, or formyl-Met-Leu-Phe (fMLP), and monocyte- or granulocyte-like PLB-D cells did not release PGE(2) with any of the agonists. The kinetics of cPLA(2) translocation to nuclear fractions in monocyte-like PLB cells stimulated with fMLP or ionomycin was in correlation with the kinetics of PGE(2) production. Granulocyte-like PLB cells, but not granulocyte-like PLB-D cells, secreted leukotriene B(4) (LTB(4)) after stimulation with ionomycin or A23187. Preincubation of monocyte-like parent PLB cells with 100 ng/ml lipopolysaccharide (LPS) for 16 h enhanced stimulated PGE(2) production, which is in correlation with the increased levels of cPLA(2) detected in these cells. LPS preincubation was less potent in increasing PGE(2) and LTB(4) secretion and did not affect cPLA(2) expression in granulocyte-like PLB cells, which may be a result of their lower levels of surface LPS receptor expression. LPS had no effect on monocyte- or granulocyte-like PLB-D cells. The lack of eicosanoid formation in stimulated, differentiated cPLA(2)-deficient PLB cells indicates that cPLA(2) contributes to stimulated eicosanoid formation in monocyte- and granulocyte-like PLB cells.

Mediterranean spotted fever in an American woman.

Mediterranean spotted fever is common in southern Europe, the Middle East, and North Africa, but is unknown in the United States. It has a clinical picture resembling Rocky Mountain spotted fever, but it is a milder disease. We report a case of Mediterranean spotted fever in a young American woman returning from Morocco and review the clinical picture of this disease.

Technetium Tc 99m diphosphonate bone scan. False-normal findings in elderly patients with hematogenous vertebral osteomyelitis.

Hematogenous osteomyelitis is usually diagnosed by an abnormal technetium Tc 99m diphosphonate bone scan in symptomatic patients who have positive blood cultures. False-normal 99mTc bone scans have been described recently in neonates with biopsy-proved osteomyelitis. This phenomenon seems to be extremely rare in adults. Two elderly patients with hematogenous vertebral osteomyelitis had normal technetium Tc 99m diphosphonate bone scans when first evaluated. In both cases the bone scans became abnormal four to six weeks after onset of symptoms and two to four weeks after the initial normal results of the study. When suggested by the clinical picture, hematogenous osteomyelitis cannot be ruled out by a normal 99mTc bone scan at any age. Gallium scan, computed tomographic scan, or bone biopsy can be helpful in such cases.

Multiple autoimmune manifestations in a splenectomized subject with HLA-B8.

Idiopathic thrombocytopenic purpura developed in a 31-year-old man, and he underwent a splenectomy because of his failure to respond to steroid therapy. Subsequently, during a six-year follow-up, chronic active hepatitis, Coombs' positive hemolytic anemia, and pulmonary interstitial fibrosis developed. Since such a clustering of autoimmune manifestations in a single subject is unusual, possible contributing factors were sought. We suggest that both the splenectomy and the histocompatibility antigen HLA-B8, which the patient was found to carry, may have contributed to this rare clinical syndrome.

Serious bacterial infections after endoscopic procedures.

Transient bacteremia during and after endoscopic procedures is a well- documented phenomenon, but complicated bacteremia such as endocarditis in patients at risk is considered to be extremely rare. The recommendations for prophylaxis before endoscopy in patients with valvular heart disease were recently released. We discuss 16 cases of complicated bacteremia that developed after endoscopy (eight cases previously published in the literature and eight cases we encountered). The endoscopic procedures were gastroscopy (five cases), sclerotherapy (six cases), sigmoidoscopy (three cases), and esophageal dilation (two cases). Fourteen patients had underlying disease: valvular heart disease (six patients), cirrhosis of the liver (five patients, one of whom also had a prosthetic knee), valvular heart disease and cirrhosis of the liver (two patients), and gastric carcinoma (one patient). The organisms involved were Streptococcus viridans (six cases), streptococcus group D (three cases), Streptococcus pneumoniae (two cases), Streptococcus microaerophilicus (two cases), Staphylococcus aureus (two cases), and Cardiobacterium hominis (one case). The patients presented with the following infections: endocarditis (12 patients), spontaneous bacterial peritonitis (two patients), septic arthritis (one patient), and brain abscess (one patient). The outcome was good in 15 patients; one patient died. Patients with valvular heart disease, cirrhosis of the liver, ascites, malignancies, or prosthetic joints who undergo endoscopic procedures should be considered for antibiotic prophylaxis.

Abnormalities in bilirubin and liver enzyme levels in adult patients with bacteremia. A prospective study.

Eighty-four patients with bacteremia were surveyed prospectively for biochemical markers of liver damage. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin levels were elevated in 44 (53%), 39 (47%), 45 (54%), and 5 (6%) of the patients on the first determination (2.0 +/- 0.1 days after onset of fever) and in 11 (13%), 17 (20%), 26 (31%), and 1 (1%) on the second determination (5.4 +/- 0.2 days after onset of fever), respectively. The elevation rarely exceeded three times the upper limit of normal. One patient had severe jaundice. An abnormality of at least one of these values was found in 55 patients (65%). There were no differences in site of infection, bacteria isolated, and outcome between patients with and without biochemical abnormalities. We conclude that in adult patients with bacteremia, elevation of liver enzymes and bilirubin is common, usually mild, of short duration, and of no prognostic significance.

Clinical features and costs of care for hospitalized adults with primary Epstein-Barr virus infection.

PURPOSE: To study the clinical and laboratory features of primary infection with the Epstein-Barr virus in adults who required hospitalization and to assess the difficulty in its diagnosis, the use of diagnostic procedures, and the associated costs of care. PATIENTS AND METHODS: We retrospectively identified all adult patients who were diagnosed with primary Epstein-Barr virus infection in our region between 1988 and 1997 using strict serologic criteria. The added costs of unnecessary diagnostic tests and treatment were estimated. RESULTS: The analysis included 47 patients (60% men) with a mean (+/-SD) age of 30 +/- 14 years. The prime cause of admission was fever (83%). Compared with patients 35 years of age and older, those younger than 35 years were more likely to have pharyngitis (45% vs 10%) and lymphadenopathy (66% vs 17%). Younger patients also had a greater mean atypical lymphocyte count (17% +/- 14% vs 8% +/- 6%) and more abnormal hepatic enzyme levels. Inpatient work-ups resulted in 309 days of hospitalization, many diagnostic tests, and unnecessary empiric treatments (total 203 days of antibiotic therapy). Overall, unnecessary diagnostic procedures and medical treatments contributed an average of approximately $12,000 in health-care costs per patient. CONCLUSIONS: Testing for primary Epstein-Barr virus infection should be a routine step in the investigation of fever in adults of all ages. A higher index of suspicion might prevent unnecessary, sometimes hazardous inpatient work-ups from being performed, thereby reducing health-care expenses.

Incidence and clinical significance of bacteremia and sepsis among cardiac patients treated with intra-aortic balloon counterpulsation pump.

In this prospective study, a significant incidence of fever (47%), true bacteremia (15%), and sepsis (12%), were found in 60 cardiac patients treated with an intra-aortic balloon counterpulsation pump. The benefit of antibiotic prophylaxis in this setting should therefore be evaluated.

Legionella species community-acquired pneumonia. A review of 56 hospitalized adult patients.

BACKGROUND: In a prospective study, Legionella species (Lsp) was identified as the causative agent in 56 (16.2%) of 346 adult patients hospitalized over the course of 1 year with community-acquired pneumonia (CAP), in the Soroka Medical Center, Beer-Sheva, Israel. OBJECTIVE: To characterize patients with Lsp CAP in our study. METHODS: The diagnosis of infection with Lsp was based on serologic testing of antibodies using the indirect immunofluorescent method. RESULTS: In 35 (62.5%) of the patients, at least one other etiologic agent for CAP was identified in addition to Lsp. The patient population was relatively young, with relatively low rates of chronic comorbidity, and a broad spectrum of disease severity compared with previously published studies. No single epidemiologic, clinical, laboratory, or radiographic characteristic differentiated between Lsp CAP and other CAP patients in our study. Three patients (5.4%) who were not treated with erythromycin died. However, in contrast, nine patients who were treated with beta-lactam antibiotics recovered completely. CONCLUSIONS: Lsp is a common cause of CAP in our region, usually as a coinfection with another causative agent. Lsp CAP, which cannot be characterized on the basis of clinical, routine laboratory, or radiographic data, requires specific microbiologic or serologic diagnosis. Treatment with erythromycin appears to be important to reduce mortality from this disease, but in a significant number of patients, the disease may be self-limited.

Epidemiology and ethnic distribution of multidrug-resistant tuberculosis in southern Israel, 1992-1997: the impact of immigration.

STUDY OBJECTIVES: To assess the incidence of tuberculosis in the native and immigrant populations of southern Israel in the period between 1992 and 1997, and to study the prevalence of drug resistance overall and among these subpopulations in the region in order to create guidelines for empirical antituberculous treatment in this region. DESIGN: A retrospective population-based study. SETTING: The southern district of the country and its tertiary-care hospital. PATIENTS: All new culture-proven tuberculosis cases diagnosed in adults residing in the Negev region during the study period. Patients were classified into four groups according to ethnic origin and immigration date. RESULTS: During the study period, 249 new cases involving 249 patients were recorded. Immigrants from the former Soviet Union (IFSU) were significantly younger and of male gender, and the incidence among this group rose sharply. IFSU had higher rates of resistance to any drug or drug combination. Isoniazid resistance rates were 16% overall and 32% among IFSU. Resistance to any drug was observed in 29% overall and 50% of isolates among IFSU. Multidrug-resistant tuberculosis was observed in 8.5% and 17%, respectively. CONCLUSIONS: The population of southern Israel carries very high rates of drug-resistant tuberculosis, mandating quadruple empiric treatment. IFSU should be regarded as having multidrug-resistant tuberculosis until proven otherwise, and empiric therapy with at least five drugs should be considered. This report demonstrates the influence of immigration on the incidence of tuberculosis, and the great value of local surveillance of population-specific resistance rates in an immigrant society, in order to optimize drug treatment and prevent the dissemination of resistant strains.

Sequential therapy with cefuroxime followed by cefuroxime axetil in community-acquired pneumonia.

STUDY OBJECTIVES: To compare the efficacy of two sequential therapy regimens of IV cefuroxime followed by oral cefuroxime axetil for the treatment of community-acquired pneumonia (CAP). DESIGN: Prospective, multicenter, randomized, open-label, parallel-group study. SETTING: Sixty-six centers in 11 countries (Belgium, Canada, Czech Republic, Germany, Hungary, Ireland, Israel, Poland, Portugal, South Africa, and the United Kingdom). PATIENTS: Six hundred thirty-six adults with CAP requiring hospitalization and initial IV antibiotic treatment. INTERVENTIONS: Cefuroxime, 1.5 g IV tid or bid for 48 to 72 h followed by oral cefuroxime axetil, 500 mg bid for 7 days. MEASUREMENTS AND RESULTS: For clinically evaluable patients, the clinical response rates were equivalent for cefuroxime tid and bid groups posttreatment (cure/improvement, 79% and 84%, respectively) and at follow-up (maintained cure, 87% and 82%, respectively). All signs and symptoms of pneumonia showed improvement at the time of switch from IV to oral therapy. A total of 111 pathogens were isolated, the most common being Streptococcus pneumoniae (23%), Haemophilus influenzae (18%), and Enterobacteriaceae (15%). Bacteriologic clearance was obtained posttreatment in 47 of 49 and 36 of 42 of bacteriologically evaluable patients in the cefuroxime tid and bid groups, respectively. Both regimens were well tolerated with a low incidence of drug-related adverse events, the most common being GI. CONCLUSIONS: Twice daily IV cefuroxime followed by oral cefuroxime axetil is a simple and effective sequential therapy regimen for the treatment of CAP. It offers potential cost savings and can replace the current tid regimen in this indication.