Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada,…

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Surgical treatment of drug-resistant tuberculosis.
Lancet Infect Dis. 2012 Feb;12…

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Diagnostic accuracy of a low-cost, urine antigen, point-of-care screening assay for HIV-associated pulmonary tuberculosis before antiretroviral therapy: a descriptive study.
Lancet Infect Dis. 2011 Oct 17;
Authors: Lawn SD, Ke…

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Predictive value of interferon-? release assays for incident active tuberculosis: a systematic review and meta-analysis.
Lancet Infect Dis. 2011 Aug 14;
Authors: Rangaka MX, Wilkinson KA, Glynn JR, Ling D, Menzies D, Mwansa-K…

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Prevention of ventilator-associated pneumonia with oral antiseptics: a systematic review and meta-analysis.
Lancet Infect Dis. 2011 Jul 26;
Authors: Labeau SO, Van de Vyver K, Brusselaers N, Vogelaers D, Blot SI
BACKGR…

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Clinical management of Staphylococcus aureus bacteraemia.

Lancet Infect Dis. 2011 Mar;11(3):208-222

Authors: Thwaites GE, Edgeworth JD, Gkrania-Klotsas E, Kirby A, Tilley R, Török ME, Walker S, Wertheim HF, Wilson P, Llewelyn MJ,

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.

PMID: 21371655 [PubMed - as supplied by publisher]

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Guidelines for hospital-acquired pneumonia and health-care-associated pneumonia: a vulnerability, a pitfall, and a fatal flaw.

Lancet Infect Dis. 2011 Mar;11(3):248-52

Authors: Yu VL

The 2005 American Thoracic Society and Infectious Disease Society of America’s guidelines for pneumonia introduced the new category of health-care-associated pneumonia, which increased the number of people to whom the guidelines for multidrug-resistant pathogens applied. Three fundamental issues inherent in the definition of hospital-acquired pneumonia and health-care-associated pneumonia undermined the credibility of these guidelines and the applicability of their recommendations: a vulnerability, a pitfall, and a fatal flaw. The vulnerability is the extreme heterogeneity of the population of patients. The fatal flaw is the failure to accurately diagnose hospital-acquired pneumonia and ventilator-associated pneumonia; inability to distinguish colonisation from infection in respiratory-tract cultures renders the guidelines inherently unstable. The pitfall is spiralling empiricism of antibiotic use for severely ill patients in whom infection might not be present. A vicious circle of antibiotic overuse leading to emergence of resistant microflora can become established, leading to unnecessary use of empirical broad-spectrum combination antibiotics and increased mortality. Controlled studies now show that administration of broad-spectrum combination antibiotic therapy can lead to increased mortality in uninfected patients. Proposed solutions include the use of individualised assessment of patients. Health-care-associated pneumonia should be broken down into several distinct subgroups so narrow-spectrum antibiotic therapy can be used. Emphasis should be placed on defining the microbial cause of the pneumonia rather than reflex administration of empirical combination therapy.

PMID: 21371658 [PubMed - in process]

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Implementation of guidelines for management of possible multidrug-resistant pneumonia in intensive care: an observational, multicentre cohort study.

Lancet Infect Dis. 2011 Jan 19;

Authors: Kett DH, Cano E, Quartin AA, Mangino JE, Zervos MJ, Peyrani P, Cely CM, Ford KD, Scerpella EG, Ramirez JA,

BACKGROUND: The American Thoracic Society and Infectious Diseases Society of America provide guidelines for management of hospital-acquired, ventilator-associated, and health-care-associated pneumonias, consisting of empirical antibiotic regimens for patients at risk for multidrug-resistant pathogens. We aimed to improve compliance with these guidelines and assess outcomes. METHODS: We implemented a performance-improvement initiative in four academic medical centres in the USA with protocol-based education and prospective observation of outcomes. Patients were assessed for severity of illness and followed up until death, hospital discharge, or day 28. We included patients in intensive-care units who were at risk for multidrug-resistant pneumonia and were treated empirically. FINDINGS: 303 patients at risk for multidrug-resistant pneumonia were treated empirically, and prescribed treatment was guideline compliant in 129 patients and non-compliant in 174 patients. 44 (34%) patients died before 28 days in the compliance group and 35 (20%) died in the non-compliance group. Five patients in the compliance group and seven in the non-compliance group were lost to follow-up after day 14. Kaplan-Meier estimated survival to 28 days was 65% in the compliance group and 79% in the non-compliance group (p=0·0042). This difference persisted after adjustment for severity of illness. Median length of stay and duration of mechanical ventilation did not differ between groups. Compliance failures included non-use of dual treatment for Gram-negative pathogens in 154 patients and absence of meticillin-resistant Staphylococcus aureus coverage in 24 patients. For patients in whom pathogens were subsequently identified, empirical treatment was active in 79 (81%) of 97 of patients receiving compliant therapy compared with 109 (85%) of 128 of patients receiving non-compliant therapy. INTERPRETATION: Because adherence with empirical treatment was associated with increased mortality, we recommend a randomised trial be done before further implementation of these guidelines. FUNDING: Pfizer, US Medical.

PMID: 21256086 [PubMed - as supplied by publisher]

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Increased risk of invasive bacterial infections in African people with sickle-cell disease: a systematic review and meta-analysis.

Lancet Infect Dis. 2010 May;10(5):329-37

Authors: Ramakrishnan M, Moïsi JC, Klugman KP, Iglesias JM, Grant LR, Mpoudi-Etame M, Levine OS

Children with sickle-cell disease are at great risk of serious infections and early mortality. Our Review investigates the association between sickle-cell disease and invasive bacterial disease among populations in Africa. We systematically searched published work extracted data on pneumonia, meningitis, and bacteraemia by sickle-cell disease status. Most studies identified lacked a control group and did not use best laboratory methods for culturing fastidious bacteria. Only seven case-control or case-cohort studies provided data on the association between invasive bacterial disease and sickle-cell disease status. For all-cause laboratory-confirmed invasive bacterial disease, the pooled odds of sickle-cell disease was 19-times greater among cases than controls. For disease caused by Streptococcus pneumoniae, the pooled odds of sickle-cell disease was 36-times greater; and for Haemophilus influenzae type b disease it was 13-times greater.

PMID: 20417415 [PubMed - indexed for MEDLINE]

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Global and regional risk of disabling sequelae from bacterial meningitis: a systematic review and meta-analysis.

Lancet Infect Dis. 2010 May;10(5):317-28

Authors: Edmond K, Clark A, Korczak VS, Sanderson C, Griffiths UK, Rudan I

Few data sources are available to assess the global and regional risk of sequelae from bacterial meningitis. We aimed to estimate the risks of major and minor sequelae caused by bacterial meningitis, estimate the distribution of the different types of sequelae, and compare risk by region and income. We systematically reviewed published papers from 1980 to 2008. Standard global burden of disease categories (cognitive deficit, bilateral hearing loss, motor deficit, seizures, visual impairment, hydrocephalus) were labelled as major sequelae. Less severe, minor sequelae (behavioural problems, learning difficulties, unilateral hearing loss, hypotonia, diplopia), and multiple impairments were also included. 132 papers were selected for inclusion. The median (IQR) risk of at least one major or minor sequela after hospital discharge was 19.9% (12.3-35.3%). The risk of at least one major sequela was 12.8% (7.2-21.1%) and of at least one minor sequela was 8.6% (4.4-15.3%). The median (IQR) risk of at least one major sequela was 24.7% (16.2-35.3%) in pneumococcal meningitis; 9.5% (7.1-15.3%) in Haemophilus influenzae type b (Hib), and 7.2% (4.3-11.2%) in meningococcal meningitis. The most common major sequela was hearing loss (33.9%), and 19.7% had multiple impairments. In the random-effects meta-analysis, all-cause risk of a major sequela was twice as high in the African (pooled risk estimate 25.1% [95% CI 18.9-32.0%]) and southeast Asian regions (21.6% [95% CI 13.1-31.5%]) as in the European region (9.4% [95% CI 7.0-12.3%]; overall I(2)=89.5%, p<0.0001). Risks of long-term disabling sequelae were highest in low-income countries, where the burden of bacterial meningitis is greatest. Most reported sequelae could have been averted by vaccination with Hib, pneumococcal, and meningococcal vaccines.

PMID: 20417414 [PubMed - indexed for MEDLINE]

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Progressive multifocal leukoencephalopathy in HIV-1 infection.

Lancet Infect Dis. 2009 Oct;9(10):625-36

Authors: Cinque P, Koralnik IJ, Gerevini S, Miro JM, Price RW

Progressive multifocal leukoencephalopathy is caused by the JC polyomavirus (JCV) and is one of the most feared complications of HIV-1 infection. Unlike other opportunistic infections, this disease can present when CD4 counts are higher than those associated with AIDS and when patients are receiving combined antiretroviral therapy, either shortly after starting or, more rarely, during long term successful treatment. Clinical suspicion of the disease is typically when MRI shows focal neurological deficits and associated demyelinating lesions; however, the identification of JCV in cerebrospinal fluid or brain tissue is needed for a definitive diagnosis. Although no specific treatment exists, the reversal of immunosuppression by combined antiretroviral therapy leads to clinical and MRI stabilisation in 50-60% of patients with the disease, and JCV clearance from cerebrospinal fluid. A substantial proportion of patients treated with combined antiretroviral therapy develop inflammatory lesions, which can be associated with either a favourable outcome or clinical worsening. The reasons for variability in the natural history of progressive multifocal leukoencephalopathy and treatment responses are largely undefined, and more specific and rational approaches to management are needed.

PMID: 19778765 [PubMed - indexed for MEDLINE]

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Rapid screening tests for meticillin-resistant Staphylococcus aureus at hospital admission: systematic review and meta-analysis.

Lancet Infect Dis. 2009 Sep;9(9):546-54

Authors: Tacconelli E, De Angelis G, de Waure C, Cataldo MA, La Torre G, Cauda R

Detection and eradication of meticillin-resistant Staphylococcus aureus (MRSA) represents a public health priority worldwide. Our aim was to do a systematic review and meta-analysis of randomised, non-randomised, and observational studies to summarise the available evidence on the effect of MRSA detection by rapid screening tests on hospital-acquired MRSA infections and acquisition rate. Eligible studies were retrieved from Medline, EmBase, Science Citation Index, and the Cochrane database. We judged as eligible those studies that compared hospitals and wards in which active screening for the detection of MRSA carriers was done at hospital admission by use of a rapid molecular test to those in which active screening was done with culture alone or not at all. To account for statistical heterogeneity between studies, random-effects models were used. Ten studies (nine interventional studies and one unblinded, cluster-randomised, crossover trial) were reviewed. Meta-analysis was done for studies reporting data on the same outcome. Primary outcomes included MRSA acquisition rate per 1000 patient-days (four studies); incidence of MRSA bloodstream infections per 1000 patient-days (three studies); and incidence of MRSA surgical-site infections per 100 surgical procedures (five studies). Compared with culture screening, use of rapid screening tests was not associated with a significant decrease in MRSA acquisition rate (risk ratio 0.87, 95% CI 0.61-1.24). Between wards applying rapid screening tests and those not applying screening, we noted a significantly decreased risk for MRSA bloodstream infections (0.54, 95% CI 0.41-0.71), but not for MRSA surgical-site infections (0.69, 95% CI 0.46-1.01). We conclude that active screening for MRSA is more important than the type of test used. Since important and costly decisions, such as mandatory legislation for MRSA universal screening, are under consideration in many countries worldwide, policy makers should be aware of the limits and the heterogeneity of the available evidence.

PMID: 19695491 [PubMed - indexed for MEDLINE]

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Emergence of community-acquired meticillin-resistant Staphylococcus aureus strain USA300 as a cause of necrotising community-onset pneumonia.

Lancet Infect Dis. 2009 Jun;9(6):384-92

Authors: Hidron AI, Low CE, Honig EG, Blumberg HM

Meticillin-resistant Staphylococcus aureus (MRSA), usually known as a nosocomial pathogen, has emerged as the predominant cause of skin and soft-tissue infections in many communities. Concurrent with the emergence of community-acquired MRSA (CA-MRSA), there have been increasing numbers of reports of community-acquired necrotising pneumonia in young patients and others without the classic health-care-associated risk factors. Community-onset necrotising pneumonia due to CA-MRSA is now recognised as an emerging clinical entity with distinctive clinical features and substantial morbidity and mortality. A viral prodrome (eg, influenza or influenza-like illness) followed by acute onset of shortness of breath, sepsis, and haemoptysis is the most frequent clinical presentation. The best treatment of this partly toxin-mediated disease has not been clearly defined. Whereas cases of CA-MRSA pneumonia have now been reported from almost every continent, the overall burden of disease of this emerging syndrome remains incompletely described. We report two related cases of community-onset pneumonia due to the MRSA USA300 genotype and review the literature regarding the emergence of CA-MRSA pneumonia.

PMID: 19467478 [PubMed - indexed for MEDLINE]

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Management of meningitis due to antibiotic-resistant Acinetobacter species.

Lancet Infect Dis. 2009 Apr;9(4):245-55

Authors: Kim BN, Peleg AY, Lodise TP, Lipman J, Li J, Nation R, Paterson DL

Acinetobacter meningitis is becoming an increasingly common clinical entity, especially in the postneurosurgical setting, with mortality from this infection exceeding 15%. Infectious Diseases Society of America guidelines for therapy of postneurosurgical meningitis recommend either ceftazidime or cefepime as empirical coverage against Gram-negative pathogens. However, assessment of the pharmacodynamics of these cephalosporins in cerebrospinal fluid suggests that recommended doses will achieve pharmacodynamic targets against fewer than 10% of contemporary acinetobacter isolates. Thus, these antibiotics are poor options for suspected acinetobacter meningitis. From in vitro and pharmacodynamic perspectives, intravenous meropenem plus intraventricular administration of an aminoglycoside may represent a superior, albeit imperfect, regimen for suspected acinetobacter meningitis. For cases of meningitis due to carbapenem-resistant acinetobacter, use of tigecycline is not recommended on pharmacodynamic grounds. The greatest clinical experience rests with use of polymyxins, although an intravenous polymyxin alone is inadvisable. Combination with an intraventricularly administered antibiotic plus removal of infected neurosurgical hardware appears the therapeutic strategy most likely to succeed in this situation. Unfortunately, limited development of new antibiotics plus the growing threat of multidrug-resistant acinetobacter is likely to increase the problems posed by acinetobacter meningitis in the future.

PMID: 19324297 [PubMed - indexed for MEDLINE]

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Current control and treatment of multidrug-resistant Acinetobacter baumannii infections.

Lancet Infect Dis. 2008 Dec;8(12):751-62

Authors: Karageorgopoulos DE, Falagas ME

Institutional outbreaks caused by Acinetobacter baumannii strains that have acquired multiple mechanisms of antimicrobial drug resistance constitute a growing public-health problem. Because of complex epidemiology, infection control of these outbreaks is difficult to attain. Identification of potential common sources of an outbreak, through surveillance cultures and epidemiological typing studies, can aid in the implementation of specific control measures. Adherence to a series of infection control methods including strict environmental cleaning, effective sterilisation of reusable medical equipment, attention to proper hand hygiene practices, and use of contact precautions, together with appropriate administrative guidance and support, are required for the containment of an outbreak. Effective antibiotic treatment of A baumannii infections, such as ventilator-associated pneumonia and bloodstream infections, is also of paramount importance. Carbapenems have long been regarded as the agents of choice, but resistance rates have risen substantially in some areas. Sulbactam has been successfully used in the treatment of serious A baumannii infections; however, the activity of this agent against carbapenem-resistant isolates is decreasing. Polymyxins show reliable antimicrobial activity against A baumannii isolates. Available clinical reports, although consisting of small-sized studies, support their effectiveness and mitigate previous concerns for toxicity. Minocycline, and particularly its derivative, tigecycline, have shown high antimicrobial activity against A baumannii, though relevant clinical evidence is still scarce. Several issues regarding the optimum therapeutic choices for multidrug-resistant A baumannii infections need to be clarified by future research.

PMID: 19022191 [PubMed - indexed for MEDLINE]

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