Cost-effectiveness of a systematic e-assessed follow-up of postoperative recovery after day surgery: a multicentre randomized trial.

BACKGROUND: Most surgeries are done on a day-stay basis. Recovery assessment by phone points (RAPP) is a smartphone-based application (app) to evaluate patients after day surgery. The aim of this study was to estimate the cost-effectiveness of using RAPP for follow-up on postoperative recovery compared with standard care. METHODS: This study was a prospective parallel single-blind multicentre randomized controlled trial. Participants were randomly allocated to the intervention group using RAPP or the control group receiving standard care. A cost-effectiveness analysis was performed based on individual data and included costs for the intervention, health effect [quality-adjusted life-years (QALYs)], and costs or savings in health-care use. RESULTS: The mean cost for health-care consumption during 2 weeks after surgery was estimated at €37.29 for the intervention group and €60.96 for the control group. The mean difference was €23.66 (99% confidence interval -46.57 to - 0.76; P=0.008). When including the costs of the intervention, the cost-effectiveness analysis showed net savings of €4.77 per patient in favour of the intervention. No difference in QALYs gained was seen between the groups (P=0.75). The probability of the intervention being cost-effective was 71%. CONCLUSIONS: This study shows that RAPP can be cost-effective but had no effect on QALY. RAPP can be a cost-effective tool in providing low-cost health-care contacts and in systematically assessing the quality of postoperative recovery. CLINICAL TRIAL REGISTRATION: NCT02492191.

Factors associated with time to clinical stability in complicated skin and skin structure infections.

OBJECTIVES: Factors associated with the time to clinical stability in patients with complicated skin and skin structure infection (cSSSI) were analysed in a retrospective population-based study. METHODS: All hospitalized patients (n=402) with cSSSI in two Nordic cities during a 4-year period were included. Patient, disease, and treatment related factors were analysed in relation to early (0-3 days) or late (≥4 days) clinical stability. Clinical stability was assessed as improvement of infection related local and systemic signs. Furthermore, the effect of antimicrobial and other treatment on achievement of clinical stability was studied. RESULTS: Clinical stability was reached within 0-3 days by 59% (239/402) of patients. In multivariable analysis later clinical stability was associated with admission to ICU (OR 10.1, 95% CI 4.01-25.3), posttraumatic wound infection (OR 3.17, 95% CI 1.31-7.69), bacteraemia (OR 3.09, 95% CI 1.36-7.02), surgical intervention after diagnosis (OR 2.64, 95% CI 1.36-5.11), diabetes (OR 2.33, 95% CI 1.28-4.25), and initial broad-spectrum antibiotic therapy (OR 3.03, 95% CI 1.43-6.40). Early stabilization within 3 days was associated with previous hospitalization (OR 0.47, 95% CI 0.22-0.99) and empirical antimicrobial therapy covering the initial pathogens (OR 0.38, 95% CI 0.18-0.80). Patients with clinical stability within 3 days were less likely to have treatment modifications and antimicrobial changes and had shorter hospital stay and antimicrobial treatment than those who stabilized later. CONCLUSIONS: This study suggests that late treatment response depends on several baseline characteristics of patients and disease related factors other than treatment related factors.

Costs and resource use following defunctioning stoma in low anterior resection for cancer - A long-term analysis of a randomized multicenter trial.

BACKGROUND: Defunctioning stoma in low anterior resection (LAR) for rectal cancer can prevent major complications, but overall cost-effectiveness for the healthcare provider is unknown. This study compared inpatient healthcare resources and costs within 5 years of LAR between two randomized groups of patients undergoing LAR with and without defunctioning stoma. METHOD: Five-year follow-up of a randomized, multicenter trial on LAR (NCT 00636948) with (stoma; n = 116) or without (no stoma; n = 118) defunctioning stoma comparing inpatient healthcare resources and costs. Unplanned stoma formation, days with stoma, length of hospital stay, reoperations, and total associated inpatient costs were analyzed. RESULTS: Average costs were € 21.663 per patient with defunctioning stoma and € 15.922 per patient without defunctioning stoma within 5 years of LAR, resulting in an average cost-saving of € 5.741. There was no difference between groups regarding the total number of days with any stoma (stoma = 33 398 vs. no stoma = 34 068). The total number of unplanned reoperations were 70 (no stoma) and 32 (stoma); p < 0.001. In the group randomized to no stoma at LAR, 30.5% (36/118) required an unplanned stoma later. CONCLUSION: Randomization to defunctioning stoma in LAR was more expensive than no stoma, despite the cost-savings associated with a reduced frequency of anastomotic leakage. Both groups required the same total number of days with a stoma within five years of LAR.

Case management at an outpatient unit for severe and enduring eating disorder patients at Stockholm Centre for Eating Disorders- a study protocol.

BACKGROUND: Patients with severe and enduring eating disorders (SEED) are seriously ill and have a low quality of life. Case management (CM), originally developed for adult patients with severe mental disabilities, has been shown to enhance social functioning and improve quality of life, while reducing the number and length of hospitalizations. In 2014, a special unit based on CM, for patients with SEED (the Eira unit) was started at Stockholm Centre for Eating Disorders, Sweden. METHOD/DESIGN: This study aims to investigate if CM can improve SEED patients' quality of life, and reduce their eating disorder symptoms as well as their health care consumption. Methods for data collection are a semi-structured diagnostic interview, self-report questionnaires, and a qualitative interview. The diagnostic interview and the self-report assessments will be done at start of treatment and at follow-ups after 1, 2, and 3years. The qualitative interview will be conducted 1 year after start of treatment. The study is approved by the ethical review board in Stockholm in compliance with the Helsinki Declaration. DISCUSSION: CM is a possible new contribution to the treatment methods for SEED. It does not aim at remission, but rather to accept life as it is, and to enhance quality of life in the presence of the ED. This study will investigate the potential benefits of this novel intervention in a special unit for SEED patients. TRIAL REGISTRATION: Clinicaltrials.gov Id: NCT02897622.

RAPP, a systematic e-assessment of postoperative recovery in patients undergoing day surgery: study protocol for a mixed-methods study design including a multicentre, two-group, parallel, single-blind randomised controlled trial and qualitative interview studies.

INTRODUCTION: Day surgery is a well-established practice in many European countries, but only limited information is available regarding postoperative recovery at home though there is a current lack of a standard procedure regarding postoperative follow-up. Furthermore, there is also a need for improvement of modern technology in assessing patient-related outcomes such as mobile applications. This article describes the Recovery Assessment by Phone Points (RAPP) study protocol, a mixed-methods study to evaluate if a systematic e-assessment follow-up in patients undergoing day surgery is cost-effective and improves postoperative recovery, health and quality of life. METHODS AND ANALYSIS: This study has a mixed-methods study design that includes a multicentre, two-group, parallel, single-blind randomised controlled trial and qualitative interview studies. 1000 patients >17 years of age who are undergoing day surgery will be randomly assigned to either e-assessed postoperative recovery follow-up daily in 14 days measured via smartphone app including the Swedish web-version of Quality of Recovery (SwQoR) or to standard care (ie, no follow-up). The primary aim is cost-effectiveness. Secondary aims are (A) to explore whether a systematic e-assessment follow-up after day surgery has a positive effect on postoperative recovery, health-related quality of life (QoL) and overall health; (B) to determine whether differences in postoperative recovery have an association with patient characteristic, type of surgery and anaesthesia; (C) to determine whether differences in health literacy have a substantial and distinct effect on postoperative recovery, health and QoL; and (D) to describe day surgery patient and staff experiences with a systematic e-assessment follow-up after day surgery.The primary aim will be measured at 2 weeks postoperatively and secondary outcomes (A-C) at 1 and 2 weeks and (D) at 1 and 4 months. TRIAL REGISTRATION NUMBER: NCT02492191; Pre-results.

Treatment of complicated skin and skin structure infections in areas with low incidence of antibiotic resistance-a retrospective population based study from Finland and Sweden.

Complicated skin and skin-structure infections (cSSSI) are a common reason for hospitalization and practically all new antimicrobial agents against Gram-positive bacteria are studied in cSSSI. The aim of this population-based observational study was to assess the treatment of patients with cSSSI in areas with a low incidence of antibiotic resistance. The study population consisted of adult residents who were treated because of cSSSI during 2008-2011 from two Nordic cities, Helsinki and Gothenburg. In the final analysis population (460 patients; mean age 60.8 years; 60.9% male) 13.3% of patients had bacteraemia, 15.9% were admitted to an Intensive Care Unit and 51.5% underwent at least one surgical intervention. Treatment failure occurred in 28.2%, initial antibiotic treatment modification to another intravenous drug in 38.5% and streamlining in 5.0% of the cases. Gram-positive bacteria were predominantly isolated, with staphylococci (24.5%) and streptococci (16.0%) being the most common aetiologies. Median overall durations of hospital stay and antimicrobial treatment were 13 and 17 days, respectively, and on average 3.5 (SD 2.1) different antibiotics were used per patient. Oral antimicrobial treatment was continued in 64.3% of patients after discharge. The overall mortality rates in 30 days and in 12 months were 4.1% and 11.8%, respectively, and 16.4% of patients had a recurrence of SSSI within 12 months. In conclusion, in this population-based study antimicrobial treatment modifications were frequent and the treatment time was longer than recommended. However, bacteraemia, clinical failure and recurrences were more common than in previous non-population-based studies.

A series of severe necrotising soft-tissue infections in a regional centre in Sweden.

BACKGROUND: Necrotising soft-tissue infections (NSTIs) are rare conditions with high morbidity and mortality. Patients with NSTIs are often transferred to tertiary hospitals, but the question of whether the potential benefits of highly specialised care outweigh the risks associated with inter-hospital transfers has been raised. METHODS: Prospective study including all patients with NSTIs treated at the intensive care unit at Sahlgrenska University Hospital/East between January 2008 and December 2011. RESULTS: Twenty-nine patients with NSTIs were identified. Their median age was 54 years and 69% were men. Major co-morbidities were present in 45%. Seventeen patients (59%) were referred from other hospitals. Only 33% of the patients were correctly diagnosed or suspected of having NSTIs in the emergency department. Group A Streptococcus was the most common microbiological finding (41%), followed by Enterobacteriaceae (17%). The median time from hospitalisation to the first dose of antibiotics was 6 h and the median time to primary surgery was 16 h. Hyperbaric oxygen therapy was given to 86%, and intravenous immunoglobulin was given in 52% of the cases. The 30-day mortality was 14% (4/29). The times to the first dose of antibiotics, intensive care unit admission and primary surgery did not differ between transferred and directly admitted patients, and there was no difference in outcome between the groups. CONCLUSIONS: Patients with NSTIs develop severe local and systemic symptoms and require extremely resource-demanding hospitalisation. Inter-hospital transfer was not associated with a delay in key interventions and could not be identified as a risk factor for adverse outcome.

Respiratory support during the influenza A (H1N1) pandemic flu in Sweden.

BACKGROUND: Acute respiratory insufficiency characterised critically ill patients during the influenza A (H1N1) pandemic 2009-2010. Detailed understanding of disease progression and outcome in relation to different respiratory support strategies is important. METHODS: Data collected between August 2009 and February 2010 for a national intensive care unit influenza registry were combined with cases identified by the Swedish Institute for Infectious Disease Control. RESULTS: Clinical data was available for 95% (126/136) of the critically ill cases of influenza. Median age was 44 years, and major co-morbidities were present in 41%. Respiratory support strategies were studied among the 110 adult patients. Supplementary oxygen was sufficient in 15% (16), non-invasive ventilation (NIV) only was used in 20% (22), while transition from NIV to invasive ventilation (IV) was seen in 41% (45). IV was initiated directly in 24% (26). Patients initially treated with NIV had a higher arterial partial pressure of oxygen/fraction of oxygen in inspired gas ratio compared with those primarily treated with IV. Major baseline characteristics and 28-day mortality were similar, but 90-day mortality was higher in patients initially treated with NIV 17/67 (25%) as compared with patients primarily treated with IV 3/26 (12%), relative risk 1.2 (95% confidence interval 0.3-4.0). CONCLUSIONS: Critical illness because of 2009 influenza A (H1N1) in Sweden was dominated by hypoxic respiratory failure. The majority of patients in need of respiratory support were initially treated with NIV. In spite of less severe initial hypoxemia, initiation of ventilatory support with NIV was not associated with improved outcome.

Ten years follow-up of health and disability in people with acute traumatic hand injury: pain and cold sensitivity are long-standing problems.

The aim of this study was to investigate health and disability in people with acute traumatic hand injury 10 years after the accident. A consecutive sample of patients from the Department of Hand Surgery was followed up by means of a postal questionnaire containing the instruments EQ-5D for assessment of health and DASH for assessment of disability. Questions were added about cold sensitivity, numbness and aesthetic problems. The 97 people with various acute hand injuries had greater problems with impairments of hand function than with limitations of activities and participation in daily life. Pain was more common than among the general Swedish population. Cold sensitivity was reported by 78% and was associated with both worse impairments and greater limitations on activity and participation. Despite problems with pain and cold sensitivity, they reported good health and a low degree of disability.

Difference in drug resistance patterns between minor HIV-1 populations in cerebrospinal fluid and plasma.

OBJECTIVE: The aim of the study was to determine to what extent unique drug resistance patterns appear in minor and major HIV-1 quasispecies in cerebrospinal fluid (CSF) as compared with blood. METHODS: Forty-four plasma and CSF samples from 13 multi-treatment-experienced patients, seven of whom provided longitudinal samples, were included in the study. The subjects had failed antiretroviral therapy including lamivudine. The reverse transcriptase (RT) gene was examined by selective real-time polymerase chain reaction (SPCR), which can detect M184I/V mutants down to 0.2% of the viral population. RESULTS: SPCR revealed differences at amino acid position 184 in the plasma/CSF populations in 12 paired samples from eight patients. One plasma sample was positive by SPCR where direct sequencing showed wild-type M184. The other 11 paired samples showed quantitative differences in the mixed populations of the mutant or wild-type M184 quasispecies. Differences in other resistance-associated mutations between plasma and CSF viruses were also found by direct sequencing. CONCLUSIONS: In multi-treatment-experienced patients with therapy failure, differences in drug resistance patterns were found frequently between plasma and CSF in both minor and major viral populations. To what extent this was a true biological phenomenon remains to be established, and the clinical relevance of these findings is yet to be determined.

Importance of enjoyment when promoting physical exercise.

The purpose of this study was to investigate the importance of enjoyment of exercise in a health care-based intervention aimed at promoting physical exercise in primary health care patients. In a controlled study design, the intervention group was offered a wide range of group exercises over 3 months, followed by support in designing their own exercise program. The control group received usual care. Enjoyment of exercise and exercise level were measured. Associations between enjoyment and exercise level were analyzed using Spearman's rank correlation coefficients. Changes in enjoyment between and within study groups were analyzed by the independent and paired t-test. Associations were found between enjoyment and exercise level (r=0.36, P<0.01), as well as between changes in enjoyment and changes in exercise level (r=0.34, P<0.01). At the 12-month follow-up, enjoyment of exercise was 25% higher in the intervention group than in the control group (P<0.01). In this group of primary health care patients, enjoyment of exercise was associated with exercise level. Enjoyment of exercise seems to be a mediator of exercise level. Furthermore, health care-based interventions seem to be able to affect enjoyment of exercise. Enjoyment of exercise may be important for the long-term effectiveness, of health care-based interventions.

Comparison of HIV-1 pol and env sequences of blood, CSF, brain and spleen isolates collected ante-mortem and post-mortem.

OBJECTIVES: HIV-1 infects the central nervous system (CNS) early in the course of infection. However, it is not known to what extent the virus evolves independently within the CNS and whether the HIV-RNA in cerebrospinal fluid (CSF) reflects the viral population replicating within the brain parenchyma or the systemic infection. The aim of this study was to investigate HIV-1 evolution in the CNS and the origin of HIV-1 in CSF. MATERIALS AND METHODS: Longitudinally derived paired blood and CSF samples and post-mortem samples from CSF, brain and spleen were collected over a period of up to 63 months from three HIV-1 infected men receiving antiretroviral treatment and presenting with symptoms of AIDS dementia complex (ADC). RESULTS: Phylogenetic analyses of HIV-1 V3, reverse transcriptase (RT) and protease sequences from patient isolates suggest compartmentalization with distinct viral strains in blood, CSF and brain. We found a different pattern of RT and accessory protease mutations in the systemic infection compared to the CNS. CONCLUSIONS: We conclude that HIV-1 may to some extent evolve independently in the CNS and the viral population in CSF mainly reflects the infection in the brain parenchyma in patients with ADC. This is of importance in understanding HIV pathogenesis and can have implications on treatment of HIV-1 patients.

Antiretroviral treatment reduces increased CSF neurofilament protein (NFL) in HIV-1 infection.

OBJECTIVE: Increased levels of the light-chain neurofilament protein (NFL) in CSF provide a marker of CNS injury in several neurodegenerative disorders and have been reported in the AIDS dementia complex (ADC). We examined the effects of highly active antiretroviral treatment (HAART) on CSF NFL in HIV-1-infected subjects with and without ADC who underwent repeated lumbar punctures (LPs). METHOD: NFL was measured by ELISA (normal reference value < 250 ng/L) in archived CSF samples from 53 patients who had undergone LPs before and after initiation of HAART. RESULTS: Twenty-one of the subjects had increased CSF NFL at baseline, with a median level of 780 ng/L and an intraquartile range (IQR) of 480 to 7300. After 3 months of treatment, NFL concentrations had fallen to normal in 48% (10/21), and the median decreased to 340 ng/L (IQR < 250 to 4070) (p < 0.001), whereas at 1 year, only 4 of 16 of the 21 subjects observed for this length still had elevated NFL levels. Thirty-two subjects had normal NFL at baseline, and all but one remained normal at follow-up. These effects on CSF NFL were seen in association with clinical improvement in ADC patients, decreases in plasma and CSF HIV-1 RNA and CSF neopterin, and increases in blood CD4 T cell counts. CONCLUSION: HAART seems to halt the neurodegenerative process(es) caused by HIV-1, as shown by the significant decrease in CSF NFL after treatment initiation. CSF NFL may serve as a useful marker in monitoring CNS injury in HIV-1 infection and in evaluating CNS efficacy of antiretroviral therapy.

Imaging of four-corner fusion (SLAC arthrodesis) of the wrist with 64-slice computed tomography.

PURPOSE: To find out whether it is possible to evaluate the healing of wrist arthrodesis, carried out with a metallic spider plate, by means of 64-slice computed tomography (CT). MATERIAL AND METHODS: 18 CT examinations were performed in 12 patients 2 weeks to 37 months following scapholunate advanced collapse (SLAC) arthrodesis fixed with a metallic plate. Ten patients also had plain films of the wrist. Radiation doses were estimated. RESULTS: Plain films were difficult to evaluate due to overprojection of the spider plate. With 64-slice CT, however, it was possible to evaluate the healing process in all patients in spite of metallic artifacts. Radiation doses were low. CONCLUSION: The healing of SLAC arthrodesis of the wrist is difficult to evaluate with conventional radiography due to the metallic plate. By means of 64-slice CT, however, it was possible to "see under" the plate in all 12 patients.

Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults.

OBJECTIVES: To study the occurrence of relapse of herpes simplex encephalitis (HSE) and to find out whether soluble activity markers in cerebrospinal fluid (CSF) indicate direct viral or immune- mediated events. METHODS: A consecutive series of 32 adult survivors of HSE were followed to determine the incidence of clinical relapse of HSE. Four patients had neurological deterioration interpreted as relapsing HSE. Four non-relapsing HSE cases were selected as matched controls. Fifty nine batched, paired CSF and serum samples from the eight HSE patients were analysed for soluble activity markers, predominantly cytokines and mediators (interferon-gamma, soluble CD8, tumour necrosis factor-alpha, and interleukin-10), amount of HSV-DNA and markers of glial and neuronal destruction (neurofilament protein, glial fibrillary acidic protein, S-100-beta, and neuron specific enolase). RESULTS: Relapse of HSE was diagnosed in 3 of 26 (12 %) acyclovir-treated patients (5 episodes during 6.1 years of followup) and in 1 of 6 vidarabine-recipients. All relapses occurred from 1 to 4 months after acute HSE, except for a second relapse after 3.3 years in one patient. Computer tomography at relapses revealed few abnormalities apart from those found during the primary disease. Intravenous acyclovir and corticosteroids were given for 7-21 days in all the relapse patients. All relapse patients seemed to recover to the pre-relapse condition. HSV-DNA was demonstrated in CSF in all patients during the acute stage but not in any of 13 CSF samples taken during relapse phases. The HSV viral load during the acute stage of HSE was not higher or of longer duration in the relapsing patients than in the non-relapsing HSE controls. The levels of sCD8 were increased in nearly all CSF samples tested with peaks of sCD8 at one month of acute HSE. In all episodes of relapse, sCD8 peaks were detected during the first week at high levels. CSF levels of neuron-specific enolase, S-100 and glial fibrillary acidic protein were markedly lower at relapse than at the acute stage of HSV-1 encephalitis. CONCLUSION: The lack of demonstrable HSV DNA in CSF, the lack of acute CSF signs and the lack of signs of neural and glia cells destruction indicate that a direct viral cytotoxicity is not the major pathogenic mechanism in relapse. Instead, the pronounced CSF proinflammatory immunological response and the relative lack of CSF anti-inflammatory cytokine IL-10 response suggest immunologically-mediated pathogenicity.

Clinical and bacteriologic efficacy of telithromycin in patients with bacteremic community-acquired pneumonia.

This retrospective analysis was performed to determine the clinical and bacteriologic efficacy of the ketolide antibacterial telithromycin in patients with community-acquired pneumonia (CAP) with pneumococcal bacteremia. Patients 13 years old with radiologically confirmed CAP and a positive blood culture for Streptococcus pneumoniae at screening were analyzed from eight multicenter Phase III/IV clinical trials. In four open-label, non-comparative studies, patients received telithromycin 800 mg once daily for 7-10 days. In four randomized, controlled, double-blind, comparative studies, patients received telithromycin 800 mg once daily for 5-10 days or a comparator antimicrobial (amoxicillin 1000 mg three times daily, clarithromycin 500 mg twice daily, or trovafloxacin 200 mg once daily) for 7-10 days. In total, 118 patients (telithromycin, 94/1061 [8.9%]; comparator, 24/244 [9.8%]) had documented pneumococcal bacteremia. Those who were treated with telithromycin achieved a clinical cure rate of 90.2% (74/82, per-protocol population); S. pneumoniae was eradicated in 77/82 (93.9%) bacteremic patients who received telithromycin and 15/19 (78.9%) comparator-treated patients. Clinical cure was also observed among telithromycin-treated bacteremic patients who were infected with penicillin- or erythromycin-resistant strains of S. pneumoniae (5/7 and 8/10, respectively). In conclusion, telithromycin achieves high clinical and bacteriologic cure rates in CAP patients with pneumococcal bacteremia.

CSF amyloid beta42 and tau levels correlate with AIDS dementia complex.

There is concern that AIDS dementia complex (ADC) may be complicated by Alzheimer disease (AD). Because AD presence and risk are related to CSF beta-amyloid(1-42) (Abeta42), total tau (t-tau), and phosphorylated tau (p-tau), the authors examined these in ADC, AD, and controls. ADC had significantly decreased CSF Abeta42 and increased t-tau and p-tau concentrations similar to AD, suggesting that ADC may be associated with AD or an AD-like process.

Effects of antiretroviral treatment on blood-brain barrier integrity and intrathecal immunoglobulin production in neuroasymptomatic HIV-1-infected patients.

OBJECTIVES: To study the effect of antiretroviral combination therapy on blood-brain barrier (BBB) integrity and intrathecal immunoglobulin G (IgG) production. METHODS: Lumbar punctures were performed on 38 neurologically asymptomatic, treatment-naive HIV-1-infected patients prior to and during treatment at intervals of approximately 4 months, 1 year and 2 years. Albumin ratio and IgG index were analysed as markers of BBB integrity and intrathecal IgG synthesis. RESULTS: HIV-1 RNA decreased to < 50 HIV-1 RNA copies/mL in the cerebrospinal fluid (CSF) of all patients and in the plasma of all but one patient. Only 5% of patients had elevated albumin ratio values at baseline, while 56% had an elevated IgG index. There was no significant reduction of the albumin ratio or the IgG index. After 2 years of treatment all patients had normal albumin ratio values, while 41% still had increased IgG index levels. CONCLUSIONS: Up to 2 years after the initiation of treatment, the favourable impact of antiretroviral combination treatment on CSF viral load was not accompanied by a similar reduction of intrathecal IgG production. BBB function, measured as the albumin ratio, was not significantly changed in this cohort of neurologically asymptomatic HIV-1-infected patients.

Telithromycin in the treatment of community-acquired pneumonia: a pooled analysis.

The efficacy of telithromycin has been assessed in six Phase III studies involving adults with mild to moderate community-acquired pneumonia (CAP) with a degree of severity compatible with oral therapy. Patients received telithromycin 800 mg once daily for 7-10 days in three open-label studies (n=870) and three randomized, double-blind, comparator-controlled studies (n=503). Comparator antibacterials were amoxicillin 1000 mg three-times daily, clarithromycin 500 mg twice daily and trovafloxacin 200 mg once daily. Clinical and bacteriological outcomes were assessed 7-14 days post-therapy. Among telithromycin-treated patients, per-protocol clinical cure rates were 93.1 and 91.0% for the open-label and comparative studies, respectively. Telithromycin treatment was as effective as the comparator agents. High eradication and clinical cure rates were observed for infections caused by key pathogens: Streptococcus pneumoniae including isolates resistant to penicillin G and/or erythromycin A (95.4%), Haemophilus influenzae (89.5%) and Moraxella catarrhalis (90%). Telithromycin was also highly effective in patients with infections caused by atypical and/or intracellular pathogens and those at increased risk of morbidity. Telithromycin was generally well tolerated. Telithromycin 800 mg once daily for 7-10 days offers a convenient and well-tolerated first-line oral therapy for the empirical treatment of mild to moderate CAP.

Efficacy and tolerability of once-daily telithromycin compared with high-dose amoxicillin for treatment of community-acquired pneumonia.

BACKGROUND: This randomized, double-blind study compared the efficacy and tolerability of the new ketolide antimicrobial telithromycin with that of high-dose amoxicillin in the treatment of community-acquired pneumonia (CAP). PATIENTS AND METHODS: Adult patients (n = 404), with signs and symptoms of CAP and radiologic confirmation were randomized to receive telithromycin 800 mg once daily (n = 199) or amoxicillin 1,000 mg three times a day (n = 205) for 10 days. Clinical and bacteriologic outcomes were assessed at post-therapy test-of-cure (days 17-24) and late post therapy (days 31-36). RESULTS: The clinical cure rate for telithromycin-treated patients (per protocol) pst therapy (days 17-24) was 141/149 (94.6%) and compared well with that for amoxicillin (137/152 (90.1%)). Subset analysis of patients (per protocol) showed high clinical cure rates for patients aged >/= 65 years (telithromycin 21/24, 87.5%; amoxicillin 22/29, 75.9%); those with documented pneumococcal bacteremia (telithromycin 10/10, 100%; amoxicillin 7/9, 77.8%); and patients with a Fine score >/= III (telithromycin 31/34, 91.2%; amoxicillin 38/47, 80.9%). Bacterial eradication rates were comparable between treatments (telithromycin 42/48, 87.5%; amoxicillin 39/45, 86.7%), with 22/23 vs 18/21 Streptococcus pneumoniae strains 9/12 vs 11/13 Haemophilus influenzae strains and all Moraxella catarrhalis isolates (five and three patients, respectively) eradicated at the test-of-cure visit. Both treatments were generally well tolerated. CONCLUSION: Telithromycin 800 mg once daily is a convenient, optimal-spectrum, first-line treatment for CAP in adults, at least as effective and well tolerated as high-dose amoxicillin.