Clinical characterization of breakthrough bacteraemia: a survey of 392 episodes

BACKGROUND: Few data are available on the clinical features of patients who develop breakthrough bacteraemia, understood as positive blood cultures despite appropriate antibiotic therapy. OBJECTIVES: To determine the clinical significance and outcome of a large series of breakthrough bacteraemia. DESIGN: Retrospective analysis of a prospectively collected database. SETTING: Two university-affiliated hospitals in Catalonia, Spain. SUBJECTS: A total of 392 individuals who suffered an episode of breakthrough bacteraemia recorded between 1997 and 2002. INTERVENTIONS: Demographic characteristics, underlying diseases, origin of infection, sources of infection, microorganisms isolated, McCabe and Jackson prognostic criteria, and mortality were analysed. RESULTS: Breakthrough bacteraemia was detected in 392 of 6324 (6.1%) episodes of bacteraemia. Eighty per cent of episodes were nosocomial. The most frequent source of infection in breakthrough bacteraemia was endovascular (70%). Coagulase-negative staphylococci, Staphylococcus aureus, and Pseudomonas aeruginosa were the most significant microorganisms involved. Nosocomial acquisition together with selected sources (central venous catheter, endocarditis and other endovascular foci), underlying conditions (neutropenia, polytraumatism, allogenic bone marrow and kidney transplantation), and particular microbial aetiologies (S. aureus, P. aeruginosa and polymicrobial) were independently associated with increased risk for developing breakthrough bacteraemia. Crude mortality rate was greater in patients with breakthrough bacteraemia (16% vs. 12.3%; P<0.05), and this condition was an independent predictor of death (OR 1.4, 95% CI, 1-1.9; P=0.04). CONCLUSIONS: In view of a case of breakthrough bacteraemia it is mandatory to search for an endovascular focus. Empiric treatment should be directed to cover S. aureus, coagulase-negative staphylococci and nonfermentative Gram-negative bacilli. Breakthrough bacteraemia is an independent predictor of death.     

Cannula-associated Staphylococcus aureus bacteraemia: outcome in relation to treatment

BACKGROUND: Despite the frequency of cannula-associated Staphylococcus aureus bacteraemia (CASAB) there is uncertainty regarding the duration of treatment required. AIM: To determine the relationship between the duration and type of treatment for CASAB and subsequent relapse with deep-seated S. aureus infection. METHODS: We prospectively studied 276 patients with CASAB. Patients were followed for at least 8 weeks after completion of antibiotic treatment. Initial and subsequent isolates of S. aureus were compared using molecular methods to determine strain similarity. Results: Initial mortality was 9% (26 of 276) and a complicating focus of infection presented during initial treatment in 6% (15 of 250) of the survivors. There were nine relapses of deep-seated infection from the strain causing the original infection. Relapses were equally common following peripheral CASAB and central CASAB. There was no relationship between the duration of treatment and the rate of relapse of deep-seated infection (P = 0.24). This observation held true regardless of whether the duration of treatment was analysed as < or = 7 versus > or = 8, < or =10 versus > or =11, or < or=14 versus > or =15 days (P = 0.62, 0.87 and 0.16, respectively). Conclusion: Episodes of peripheral CASAB pose an equal risk of relapse to central cannula-related episodes. Although further studies are needed to determine the optimal treatment of CASAB, our study strongly suggests that more than 14 days treatment is excessive for most patients who respond promptly to cannula removal and antibiotic treatment.     

The efficacy of levofloxacin based triple therapy for Helicobacter pylori eradication]

BACKGROUND/AIMS: The failure rates of first and second line therapies of Helicobacter pylori (H. pylori) eradication range from 15 to 20%. This study was aimed to evaluate the efficacy and safety of levofloxacin based triple therapy compared with standard triple or quadruple therapy for H. pylori eradication in Korea. METHODS: We enrolled two hundred and sixty seven patients with presence of H. pylori infection. One hundred and forty-one patients were treated with levofloxacin based triple therapy (LAP; levofloxacin, amoxicillin, proton pump inhibitor; PPI), and 126 patients were treated with standard triple therapy (CAP; clarithromycin, amoxicillin, PPI). We retreated the patients who had failed in H. pylori eradication with standard quadruple second-line therapy (MTPB; metronidazole, tetracycline, PPI, bismuth subcitrate) or levofloxacin based therapy (LAP or LCP; levofloxacin, clarithromycin, PPI). RESULTS: In first line therapy of H. pylori eradication, the eradication rates of levofloxacin based triple therapy and standard triple therapy were 69.8% and 74.0% respectively (p=0.52). In second-line therapy, the eradication rate of levofloxacin based triple therapy and standard quadruple therapy were 62.5% and 40.0% respectively (p=0.34). CONCLUSIONS: Levofloxacin based triple therapy is effective as standard regimen to eradicate H. pylori infection and is useful for an alternative rescue therapy as well.     

Clinical management of Staphylococcus aureus bacteraemia

Staphylococcus aureus bacteraemia is one of the most common serious bacterial infections worldwide. In the UK alone, around 12,500 cases each year are reported, with an associated mortality of about 30%, yet the evidence guiding optimum management is poor. To date, fewer than 1500 patients with S aureus bacteraemia have been recruited to 16 controlled trials of antimicrobial therapy. Consequently, clinical practice is driven by the results of observational studies and anecdote. Here, we propose and review ten unanswered clinical questions commonly posed by those managing S aureus bacteraemia. Our findings define the major areas of uncertainty in the management of S aureus bacteraemia and highlight just two key principles. First, all infective foci must be identified and removed as soon as possible. Second, long-term antimicrobial therapy is required for those with persistent bacteraemia or a deep, irremovable focus. Beyond this, the best drugs, dose, mode of delivery, and duration of therapy are uncertain, a situation compounded by emerging S aureus strains that are resistant to old and new antibiotics. We discuss the consequences on clinical practice, and how these findings define the agenda for future clinical research.     

Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus non-carriers

Staphylococcus aureus is the second most frequent cause of nosocomial blood infections. We screened 14008 non-bacteraemic, non-surgical patients for S aureus nasal carriage at admission, and monitored them for development of bacteraemia. Nosocomial S aureus bacteraemia was three times more frequent in S aureus carriers (40/3420, 1.2%) than in non-carriers (41/10588, 0.4%; relative risk 3.0, 95% CI 2.0-4.7). However, in bacteraemic patients, all-cause mortality was significantly higher in non-carriers (19/41, 46%) than in carriers (seven/40, 18%, p=0.005). Additionally, S aureus bacteraemia-related death was significantly higher in non-carriers than in carriers (13/41 [32%] vs three/40 [8%], p=0.006). S aureus nasal carriers and non-carriers differ significantly in risk and outcome of nosocomial S aureus bacteraemia. Genotyping revealed that 80% of strains causing bacteraemia in carriers were endogenous.     

Epidemiological and clinical characteristics of bacteraemia caused by Aeromonas spp. as compared with Escherichia coli and Pseudomonas aeruginosa

We reviewed 75 episodes of Aeromonas spp. bacteraemia observed at our institution in 1979-2002, with special reference to episodes occurring in elderly patients (> or = 65 y) and to nosocomial episodes. In addition, we compared monomicrobial bacteraemic episodes caused by Aeromonas spp. (n = 54) with those caused by Escherichia coli (n = 108) and Pseudomonas aeruginosa (n = 108), to assess differences in clinical presentation and outcome. The 75 episodes of Aeromonas spp. bacteraemia occurred mainly in males (72%), suffering from chronic liver disease (36%) or neoplasm (33%). They had an abdominal origin in 52% of cases, were recorded as primary bacteraemia in 40%, and showed a 30-d case fatality rate of 36%. 22 episodes (29%) were nosocomial, 36 (48%) occurred in elderly patients and 21 (28%) were polymicrobial infections. In comparison with Aeromonas spp., E. coli bacteraemia was more often associated with less severe underlying conditions, a community-acquired infection (74%), and a urinary tract (52%) or abdominal (27%) origin and had a 30-d case fatality rate of 24%. P. aeruginosa bacteraemia occurred mainly in patients with severe underlying conditions, was associated with nosocomial infection (69%), and had a 30-d case fatality rate of 43%. In conclusion, Aeromonas spp. bacteraemia is a serious infection that should be considered in patients with chronic liver disease or neoplasm. It may occur in the elderly and as a nosocomial infection, and differs in clinical findings from bacteraemia due to other common pathogens.     

Levofloxacin based triple therapy as a second-line treatment after failure of Helicobacter pylori eradication with standard triple therapy

BACKGROUND: Successful eradication of Helicobacter pylori infection after failure of standard triple therapy is difficult. The efficacy and safety of levofloxacin based triple therapy as a first-line therapy has-been studied. AIMS: The aim was to evaluate the efficacy and tolerability of levofloxacin based therapy after a failed standard triple therapy. PATIENTS: We conducted a prospective, uncontrolled study of a consecutive series of 33 patients who failed eradication with 1 week of lansoprazole-amoxicillin-clarithromycin triple therapy. METHODS: The subjects were retreated with 1 week of LA-LVFX triple therapy (lansoprazole, 30 mg twice daily; amoxicillin, 1000 mg twice daily: levofloxacin, 200 mg twice daily). Cure of infection was defined as negative results from culture, histology and a urea breath test 4 to 8 weeks after the second-line therapy. RESULTS: The eradication rate was 69.7% (23/33) by both intention-to-treat and per-protocol analyses (95% confidence interval=61-79%). Seven (21.2%) patients experienced mild side-effects, such as soft stools and taste disturbance. No patient stopped the medication on account of adverse effects. CONCLUSIONS: Levofloxacin based triple therapy is an effective second-line treatment after a failed standard triple therapy.     

Early predictors of mortality in pneumococcal bacteraemia

OBJECTIVES: Pneumococcal bacteraemia carries a mortality of about 20%. Approximately 50% of deaths from pneumococcal bacteraemia occur within the first 48 h of admission. In order to influence outcome, critically ill patients should be identified at the time of presentation. This study enables the clinician to rapidly make an evidence-based assessment of a patient's prognosis, allowing the identification of patients who should be placed in a high-risk category at an early stage, when appropriate management is most likely to be effective. METHODS: Data were collected from the medical record of history, physical examination, radiological examination and laboratory investigations done on initial presentation using a standardized proforma. The data were first examined by Pearson's Chi-squared test, with Yates' correction if needed. Variables found to be significantly associated with case fatality ( P < 0.05) by these methods were examined by stepwise logistic regression analysis in order to identify those factors which were independent predictors of case fatality. RESULTS: The overall case fatality was 21%. Older age, apyrexia, tachypnoea, bilateral consolidation, hypoalbuminaemia, elevated aminotransferases, renal impairment, acidosis and leucopaenia were significantly associated with higher case fatality. Older age, acidosis and elevated serum alanine aminotransferase (ALT) were independent predictors of case fatality. Fifty-five percent of isolates belonged to serotypes 4, 6B, 9V, 14, 19F and 23F, to which good antibody levels have been documented in both young and elderly patients post-vaccination. Serotype 14 was most common, and was significantly associated with higher case fatality. Colder weather was associated with a higher incidence of both infection and case fatality. The case fatality amongst patients receiving ITU management was 44%. Less than 50% of patients who died received ITU management. CONCLUSIONS: Despite the increased availability of new antibiotics and vaccines, the mortality of patients with pneumococcal bacteraemia remains unchanged. The parameters above allow early identification of patients with a higher case fatality; these patients may benefit from being placed in a "high-risk" category early on in their management. Vaccination of the elderly may reduce the incidence and/or mortality from pneumococcal bacteraemia. Further studies are required to understand the reasons for referral for intensive therapy in acute pneumococcal bacteraemia and whether ITU management affects outcome.     

Clinical impact of rapid oxacillin susceptibility testing using a PCR assay in Staphylococcus aureus bactaeremia

OBJECTIVES: The aim of this work was to establish the clinical impact of rapid oxacillin susceptibility testing in nosocomial Staphylococcus aureus bacteraemia. METHODS: This study was performed in 145 critically ill patients infected by S. aureus. Patients were randomly assigned to one of two groups: patients for whom susceptibility testing was performed using a rapid same day multiplex PCR assay for detection of the staphylococcal mecA (mean delay of response: 6 h) and those for whom testing was accomplished using traditional overnight techniques (21 h). RESULTS: The results of this study showed no significant difference between the two groups in terms of age, Simplified Acute Physiologic Score, severity of infection, severity of underlying disease and clinical outcome (control vs. PCR): unfavourable outcome of infection, 12.32 vs. 12.5%; 95% CI for the difference = -11.49 to 11.09 (P = 0.975); unfavourable general outcome, 16.43 vs. 20.83%; 95% CI for the difference = -17.35 to 8.50 (P = 0.497). For the oxacillin-susceptible S. aureus bactaeraemia, results were: unfavourable outcome of infection = 13.04 vs. 11.11%; 95% CI for the difference = -11.38 to 16.18 (P = 0.767); unfavourable general outcome = 13.04 vs. 20.37%; 95% CI for the difference = -22.12 to 8.07 (P = 0.331). CONCLUSION: This study seemed to demonstrate that rapid oxacillin susceptibility testing using a PCR assay did not have a major impact on the care and outcome of patients with S. aureus bactaeremia.     

Rapid control of an outbreak of Staphylococcus aureus on a neonatal intensive care department using standard infection control practices and nasal mupirocin

BACKGROUND: Staphylococcus aureus is a common pathogen in neonatal intensive care departments, causing significant morbidity, mortality, and cost. Frequently, S aureus outbreaks may last for months or years. After a cluster of 4 clinically significant S aureus infections in a 7-day period in our 35-bed neonatal intensive care department, we immediately introduced standard outbreak control measures. Unique to our approach was the addition of immediate nasal mupirocin treatment of all staff members and selected patients. METHODS: Patients were screened for S aureus colonization and were cohorted with separate caregivers. S aureus isolates were submitted to a reference laboratory for pulse-field gel electrophoretic typing. Infection control practices were emphasized and education was provided for staff, physicians, and parents of patients. All caregivers and selected patients were treated immediately with nasal mupirocin. Cohorting was maintained until all patients who were colonized or infected were discharged. RESULTS: A total of 5 patients were found to be infected and 4 of 19 patients tested were found to be colonized during the study period. Patients who were infected were successfully treated. Secondary colonization and infection did not occur after implementation of controls. CONCLUSIONS: Rapid and comprehensive implementation of standard outbreak controls along with immediate treatment of direct care staff and patients with nasal mupirocin successfully controlled this outbreak within 4 weeks and no further cases have been noted.     

Impact of the use of aminoglycosides in combination antibiotic therapy on septic shock and mortality due to Staphylococcus aureus bacteremia

BACKGROUND: The purpose of this study was to evaluate the possible impact of antimicrobial combination regimens containing an aminoglycoside (AG) on morbidity and mortality associated with S. aureus bacteremia. METHODS: All inpatients over 18 years of age with S. aureus bacteremia were prospectively enrolled in three tertiary care hospitals in France and Ireland. Patients were included in the group "treated with AG" if they received at least 24 h of aminoglycoside therapy within 7 days after a positive blood culture in combination with an effective antimicrobial against the S. aureus. A Cox's proportional hazard model was used in univariate and multivariate survival analysis, the covariate "treatment with AG" being introduced as a time-dependent covariate. RESULTS: Nine percent of the 90 patients who received AG died because of infection versus 13% in the group that did not receive a combination including an AG (p>0.05). In the multivariate Cox model, stratified by septic shock and controlling for age and Charlson-weighted index of comorbidity, the adjusted odds ratio for death due to S. aureus infection associated with the use of AG was 0.6 [95% CI: (0.2-1.9); p=0.4]. However, AG was found to have a protective effect on septic shock occurrence [OR=0.3; 95% CI: (0.1-0.7), p=0.004], controlling for age, portal of entry not related to catheter infection, and diabetes. CONCLUSION: Although there was no decrease in mortality due to S. aureus infection in patients treated with AG therapy, we found a significant benefit of AG in preventing septic shock. This data argues for the early use of AG in patients with S. aureus bacteremia.     

Management of Gram-positive bacteraemia

PURPOSE OF REVIEW: Gram-positive bacteraemic infections are frequent and associated with high morbidity and mortality. This paper reviews publications focusing exclusively on new findings related to Gram-positive bacteraemia in the published literature from July 2006 to June 2007. RECENT FINDINGS: Ninety-eight articles have been reviewed. Of the 66 incorporated in this review, 21 focused on epidemiology or prevention. Thirty-two concerned staphylococcal bacteraemia, while 11 addressed other Gram-positive pathogens. There were seven articles on daptomycin, nine on endocarditis, seven on diagnostic issues, five on haemodialysis-related bacteraemia, and four on antibiotic lock techniques. SUMMARY: In contrast to the large amount of articles dealing with epidemiological issues, the past year did not reveal any new fundamental insights into the treatment of Gram-positive bacteraemia. The rise in the minimal inhibitory concentrations of Staphylococcus aureus to vancomycin may become a threat. Several publications underlined the in-vivo efficacy of daptomycin, the new kid on the block against Gram-positive bacteraemia and endocarditis. The antibiotic lock technique showed some promising potential for secondary prevention or treatment of catheter-related infection, while rapid molecular techniques for early species identification may become a valuable diagnostic tool. Most evidence was not based on large, randomized trials and needs future confirmation.     

Clinical significance of Staphylococcus aureus infection in patients with chronic liver diseases

Background: Staphylococcus aureus increasingly is recognized as an important pathogen in patients with chronic liver diseases. The purpose of this study was to evaluate clinical features and the outcome of S. aureus infections in patients with chronic liver diseases. Methods: From the database of a surveillance study for S. aureus infections, the data regarding S. aureus infections in patients with chronic liver diseases were analysed and compared with those in patients with other diseases. Results: We identified 298 patients who had chronic liver diseases; 151 (50.7%) patients had cirrhosis, 76 (25.5%) had chronic hepatitis and the remaining 71 (23.8%) had other diseases. The most common type of S. aureus infection in patients with chronic liver diseases was primary bacteraemia (n=68, 22.8%) and 92 (30.9%) patients had concomitant bacteraemia. When compared with other disease group, bacteraemia and bone infection were more frequent in the liver disease group (P<0.05). The 30‐day mortality rate of the liver disease group was significantly higher than that of the other disease group (29.4 vs. 16.7%, P<0.001). A multivariate analysis showed that chronic liver disease was a significant factor associated with mortality, along with old age, immunosuppressive treatment, intubated state, indwelling urinary catheter, pneumonia and concomitant bacteraemia. Conclusions: Bacteraemia was the most common type of S. aureus infection in patients with underlying liver diseases, predicting higher mortality rates. The mortality rate of patients with liver diseases was significantly higher than that of patients with other diseases when S. aureus infection developed.     

Brucella bacteraemia: clinical and laboratory observations in 160 patients

OBJECTIVES: To describe the clinical, serological, and prognostic features of bacteraemic brucellosis in an endemic region. METHODS: Retrospective case series of 160 patients admitted from 1983 to 1995 to a hospital providing secondary and tertiary level medical care in Saudi Arabia. All patients had positive blood cultures for Brucella species, predominantly Brucella melitensis. RESULTS: Bacteraemia was documented in 38% of 545 cases of brucellosis admitted to our institution during the study period. The main clinical syndromes were febrile illness alone (44%) or fever with arthritis (42%). Of 68 isolates that were speciated, 93% were Brucella melitensis. Initial agglutinating antibody titre was > or =1:320 in 96% of the patients. Antimicrobial resistance of B.melitensis isolates was: co-trimoxazole, 29%; rifampicin, 3.5%; streptomycin, 0.6%; and tetracycline, 0.6%. No increase in resistance was noted over the 13-year study period. Commonly used antimicrobial regimens consisted of streptomycin plus tetracycline or rifampicin plus doxycycline given for 6 weeks. Seven patients (5%) had relapse of their symptoms after antimicrobial therapy. Three of these had infective endocarditis with repeated bacteraemia. These patients required aortic valve replacement and recovered after surgery. The remaining four patients responded to a second course of therapy. CONCLUSIONS: Brucella bacteraemia is an acute febrile disease often associated with rheumatologic complaints. Most patients have an agglutinating antibody titre > or =1:320 and respond well to standard chemotherapy regimens with low mortality.     

The bacteriology of pleural infection by genetic and standard methods and its mortality significance

BACKGROUND: Antibiotic choices for pleural infection are uncertain as its bacteriology is poorly described. METHODS: Pleural fluid from 434 pleural infections underwent standard culture and a screen for bacteria by amplification and sequencing of bacterial 16S ribosomal RNA gene. RESULTS: Approximately 50% of community-acquired infections were streptococcal, and 20% included anaerobic bacteria. Approximately 60% of hospital-acquired infections included bacteria frequently resistant to antibiotics (methicillin-resistant Staphylococcus aureus, 25%; Enterobacteriaceae, 18%; Pseudomonas spp., 5%, enterococci, 12%). Mortality was increased in hospital-acquired infection (hospital, 17/36 [47%]; community, 53/304 [17%]; relative risk, 4.24; 95% confidence interval, 2.07-8.69; p < 0.00001; chi(2), 1 df = 17.47) and in gram-negative (10/22 [45%]), S. aureus (15/34 [44%]), or mixed aerobic infections (13/28 [46%]), compared with streptococcal infection (23/137 [17%]) and infection including anaerobic bacteria (10/49 [20%]; p < 0.00001, chi(2), 4 df = 23.35). CONCLUSION: Pleural infection differs bacteriologically from pneumonia and requires different treatment. Antibiotics for community-acquired infection should treat aerobic and anaerobic bacteria. Hospital-acquired, gram-negative S. aureus and mixed aerobic infections have a high mortality rate.     

Severe malaria and concomitant bacteraemia in children admitted to a rural Mozambican hospital

Objectives  To describe the prevalence, aetiology and prognostic implications of coexisting invasive bacterial disease in children admitted with severe malaria in a rural Mozambican Hospital.
Methods  Retrospective study of data systematically collected from June 2003 to May 2007 in a rural Mozambican hospital, from all children younger than 5 years admitted with severe malaria.
Results  Seven thousand and forty-three children were admitted with a diagnosis of malaria. 25.2% fulfilled the criteria for severe malaria. 5.4% of the children with severe malaria and valid blood culture results had a concomitant bacteraemia. Case fatality rates of severe malaria cases rose steeply when bacteraemia was also present (from 4.0% to 22.0%, P  < 0.0001), and bacteraemia was an independent risk factor for death among severe malaria patients (adjusted OR 6.2, 95% CI 2.8–13.7, P  = 0.0001). Streptococcus pneumoniae , Gram-negative bacteria, Staphilococcus aureus and non-typhoid Salmonella (NTS) were the most frequently isolated microorganisms among severe malaria cases. Their frequency and associated case fatality rates (CFR) varied according to age and to syndromic presentation. Streptococcus pneumoniae had a relatively low CFR, but was consistently associated with severe malaria syndromes, or anaemia severity groups. No clear-cut relationship between malarial anaemia and NTS bacteraemia was found.
Conclusions  The coexistence of malaria and invasive bacterial infections is a frequent and life-threatening condition in many endemic African settings. In Mozambique, S. pneumoniae is the leading pathogen in this interaction, possibly as a consequence of the high HIV prevalence in the area. Measures directed at reducing the burden of both those infections are urgently needed to reduce child mortality in Africa.     

Successful salvage therapy with daptomycin after linezolid and vancomycin failure in a liver transplant recipient with methicillin-resistant Staphylococcus aureus endocarditis

Abstract: Infective endocarditis is a rare complication affecting solid organ transplant recipients. Staphylococcus aureus is a common cause of infective endocarditis accounting for about 30% of cases. We present a case of nosocomial methicillin-resistant S. aureus endocarditis with persistent bacteremia, in a patient following orthotopic liver transplantation. We were unable to eradicate this infection with primary linezolid therapy or with secondary treatment with combined vancomycin and rifampicin, but successfully treated it with daptomycin, in addition to tricuspid and aortic valve replacement.     

Successful treatment of right-sided native valve methicillin-resistant Staphylococcus aureus endocarditis and septicaemia with teicoplanin and rifampicin: a case report

Vancomycin is the drug of choice in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. However, the presence of certain clinical complications like renal failure alters vancomycin pharmacokinetics, leading to drug accumulation and toxicity. This highlights the need to identify an effective substitute for treating MRSA infections when vancomycin cannot be used. We report the case of a 57-y-old Indian male diagnosed with tricuspid valve endocarditis with septicaemia and a right upper lobe cavity caused by MRSA. The patient also presented with renal failure, which precluded the use of vancomycin for treatment. A 6-week regimen of teicoplanin and rifampicin was used instead, and the infection was successfully treated. This case report provides evidence of the effectiveness of teicoplanin and rifampicin in the treatment of MRSA bacteraemia in situations where the use of vancomycin is contraindicated.     

Influence of anti-tuberculosis drug resistance on the treatment outcome of pulmonary tuberculosis patients receiving DOTS in Riyadh, Saudi Arabia.

OBJECTIVE: To determine the influence of anti-tuberculosis drug resistance existing prior to treatment on the outcome of pulmonary tuberculosis patients receiving standard short-course chemotherapy (SCC) under direct observation under national programme guidelines. DESIGN: Treatment outcomes of sputum smear- and culture-positive pulmonary tuberculosis patients admitted consecutively from 1998 through 1999 in a referral hospital in Riyadh, Saudi Arabia, were reviewed retrospectively. RESULTS: A total of 515 patients were reviewed; 139 patients were deported or transferred out. Treatment outcomes and follow-up for about 2 years were analysed for the remaining 376 patients. Among 315 patients with sensitive isolates, 301 achieved favourable outcome, none relapsed or failed, 10 defaulted, one died and three were lost to follow-up at 6 months. Mono-resistance to isoniazid, streptomycin or ethambutol did not influence the treatment outcome. All the 18 patients with mono-resistance to rifampicin were cured, but two relapsed later. Among 39 patients with any rifampicin resistance, 37 patients had favourable outcome and two failed treatment; three later relapsed. Among eight patients with MDR-TB, six had favourable outcome and two failed treatment; one later relapsed. Sputum smear conversion rates at the end of 3 months of treatment in patients with any rifampicin resistance or with multidrug resistance were inferior to those of patients with sensitive strains (89.8% vs. 96.3%, P = 0.016 and 80% vs. 96.3%, P = 0.008, respectively). CONCLUSIONS: Anti-tuberculosis drug resistance existing prior to treatment, especially rifampicin and multidrug resistance, has an adverse effect on treatment outcome, even with directly observed standard SCC under national programme guidelines.     

Open-label, randomized comparison trial of long-term outcomes of levofloxacin versus standard antibiotic therapy in acute exacerbations of chronic obstructive pulmonary disease

BACKGROUND AND OBJECTIVE: This study investigated whether treating acute exacerbations of COPD (AE-COPD) with levofloxacin modifies the long-term outcome of COPD patients in comparison with standard antibiotic regimens. METHODS: A 6-month open-label clinical trial of AE-COPD patients compared the outcomes of treating with levofloxacin versus standard therapy (clarithromycin, cefuroxime, or amoxicillin/clavulanate) at recommended doses for 10 days. Several variables were analysed: pulse oximetry, FEV1, health-related quality of life, infection-free interval, number of exacerbations, hospitalizations due to an exacerbation and mortality. RESULTS: Of the 116 patients initially enrolled, completion or withdrawal information was available for 50 patients in the levofloxacin arm and 52 in the standard therapy arm. At the end of the study, there were no differences in mortality (17.8% vs. 22.9%, P = 0.53), number of exacerbations (33 vs. 41, P = 0.40), pulse oximetry (median 91.71% vs. 92.46%, P = 0.18), FEV1 (median 51.31% vs. 47.14%, P = 0.30), health-related quality of life (median 8.63 vs. 10.75, P = 0.94) and infection-free interval (median 112 vs. 101 days, P = 0.72), for the levofloxacin and standard therapy, respectively. However, 12 out of 33 (33.6%) exacerbations treated with levofloxacin required in-hospital management versus 27 out of 41 (65.8%) treated with standard therapy (P = 0.02). CONCLUSION: This preliminary study suggests that 10-day treatment of AE-COPD with levofloxacin is associated with a reduction in hospitalizations compared with standard antibiotics despite there being no significant benefit in other outcome variables.