Posts filed under ‘Bacteriemias’

Treatment of infections caused by multidrug-resistant Gram-negative bacteria: report of the British Society for Antimicrobial Chemotherapy/Healthcare Infection Society/British Infection Association Joint Working Party

Journal of Antimicrobial Chemotherapy March 2018 V.73 Suppl 3

Peter M Hawkey; Roderic E Warren; David M Livermore; Cliodna A M McNulty; David A Enoch …

The Working Party makes more than 100 tabulated recommendations in antimicrobial prescribing for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) and suggest further research, and algorithms for hospital and community antimicrobial usage in urinary infection.

The international definition of MDR is complex, unsatisfactory and hinders the setting and monitoring of improvement programmes. We give a new definition of multiresistance.

The background information on the mechanisms, global spread and UK prevalence of antibiotic prescribing and resistance has been systematically reviewed.

The treatment options available in hospitals using intravenous antibiotics and in primary care using oral agents have been reviewed, ending with a consideration of antibiotic stewardship and recommendations.

The guidance has been derived from current peer-reviewed publications and expert opinion with open consultation. Methods for systematic review were NICE compliant and in accordance with the SIGN 50 Handbook; critical appraisal was applied using AGREE II.

Published guidelines were used as part of the evidence base and to support expert consensus. The guidance includes recommendations for stakeholders (including prescribers) and antibiotic-specific recommendations.

The clinical efficacy of different agents is critically reviewed. We found there are very few good-quality comparative randomized clinical trials to support treatment regimens, particularly for licensed older agents. Susceptibility testing of MDR GNB causing infection to guide treatment needs critical enhancements.

Meropenem- or imipenem-resistant Enterobacteriaceae should have their carbapenem MICs tested urgently, and any carbapenemase class should be identified: mandatory reporting of these isolates from all anatomical sites and specimens would improve risk assessments. Broth microdilution methods should be adopted for colistin susceptibility testing.

Antimicrobial stewardship programmes should be instituted in all care settings, based on resistance rates and audit of compliance with guidelines, but should be augmented by improved surveillance of outcome in Gram-negative bacteraemia, and feedback to prescribers.

Local and national surveillance of antibiotic use, resistance and outcomes should be supported and antibiotic prescribing guidelines should be informed by these data.

The diagnosis and treatment of both presumptive and confirmed cases of infection by GNB should be improved.

This guidance, with infection control to arrest increases in MDR, should be used to improve the outcome of infections with such strains.

Anticipated users include medical, scientific, nursing, antimicrobial pharmacy and paramedical staff where they can be adapted for local use.




March 24, 2018 at 11:05 am

Recommendations From the 2016 Guidelines for the Management of Adults With Hospital-Acquired or Ventilator-Associated Pneumonia.

P T. 2017 Dec;42(12):767-772.

Kumar ST, Yassin A, Bhowmick T, Dixit D.


Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) continue to represent the most common nosocomial-associated infections, resulting in significant attributable mortality, increased length of hospital stay, and financial burden.1 The updated Infectious Diseases Society of America (IDSA) guidelines provide guidance on the diagnosis and management of nonimmunocompromised hosts with HAP and VAP.


March 24, 2018 at 11:02 am

Treatment guidelines and outcomes of hospital-acquired and ventilator-associated pneumonia.

Clin Infect Dis. 2010 Aug 1;51 Suppl 1:S48-53.

Torres A1, Ferrer M, Badia JR.

Author information

1 Pneumology Department, Clinic Institute of Thorax, Hospital Clinic of Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Ciber de Enfermedades Respiratorias, Barcelona, Spain.

Erratum in

Clin Infect Dis. 2010 Nov 1;51(9):1114.


Hospital-acquired pneumonia is the second most frequent nosocomial infection and the first in terms of morbidity, mortality, and cost. In recent years, international societies and, most recently, the American Thoracic Society jointly with the Infectious Disease Society of America, have developed guidelines for the management of hospital-acquired pneumonia, health care-associated pneumonia, and ventilator-associated pneumonia. These guidelines include recommendations for risk stratification, initial and definitive antibiotic treatment, and prevention. The validation of these guidelines is important because it confirms that they can be used in clinical practice, as quality indicators, and as a standard of care. Several processes can be validated and are included in the guidelines, such as the accuracy of the prediction of microorganisms according to stratification criteria and the impact of guidelines on outcomes, including length of hospital and intensive care unit stay, duration of mechanical ventilation, complications, and in-hospital and 30-day mortality. Clinical studies have shown that the accuracy of predicting microorganisms according to risk stratification is reliable ( approximately 80% and approximately 90%). Three studies suggest that the implementation of guidelines, with a special emphasis on antibiotic treatment, improves several parameters of outcome. Only one study, using a before-and-after design, showed a decrease in 14-day mortality after guidelines implementation. A key issue for these studies is to modify recommendations according to local patterns of microbiology and drug resistance. In summary, implementation of guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia decreases the rate of initial inappropriate antibiotic treatment and decreased 14-day mortality in a study. More clinical studies to validate the influence of guidelines on outcome are warranted.


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March 24, 2018 at 11:00 am

Is linezolid superior to vancomycin for complicated skin and soft tissue infections due to methicillin-resistant Staphylococcus aureus?

Antimicrob Agents Chemother. 2006 May;50(5):1910; author reply 1910-1.

Kalil AC, Puumala S, Stoner J.


March 24, 2018 at 10:59 am

Is cytomegalovirus reactivation increasing the mortality of patients with severe sepsis?

Crit Care. 2011;15(2):138.

Kalil AC1, Florescu DF.

Author information

1 Department of Internal Medicine, University of Nebraska Medical Center, 985400 Nebraska Medical Center, Omaha, NE 68198, USA.


Cytomegalovirus (CMV) is a ubiquitous virus present in approximately two-thirds of the healthy population.

This virus rarely causes an active disease in healthy individuals, but it is among the most common opportunistic infections in immunocompromised patients such as solid organ transplant recipients, patients receiving chemotherapy for cancer or patients with human immunodeficiency virus.

Critically ill patients who are immunocompetent before intensive care unit admission may also become more prone to develop active CMV infection if they have prolonged hospitalizations, high disease severity, and severe sepsis.

The development of active CMV infection in these critically ill patients has been associated with a significantly higher risk of death in several previous studies.

The present issue of Critical Care brings a new study by Heininger and colleagues in which the authors found that patients with severe sepsis who developed active CMV infection had significantly longer intensive care unit and hospital stays, prolonged mechanical ventilation, but no changes in mortality compared to patients without CMV infection.

We discuss the possible reasons for their findings (for example, selection bias and low (20%) statistical power to detect mortality endpoints), and also perform an update of our previous meta-analysis with the addition of Heininger and colleagues’ study to verify whether the higher mortality rate with CMV holds.

Our updated meta-analysis with approximately 1,000 patients shows that active CMV infection continues to be associated with a significant 81% higher mortality rate than that in critically ill patients without active CMV infection.


March 24, 2018 at 10:58 am

Linezolid versus vancomycin or teicoplanin for nosocomial pneumonia: a systematic review and meta-analysis.

Crit Care Med. 2010 Sep;38(9):1802-8.

Kalil AC1, Murthy MH, Hermsen ED, Neto FK, Sun J, Rupp ME.

Author information

1 University of Nebraska Medical Center, Omaha, NE, USA.



Compared with glycopeptides, linezolid achieves higher lung epithelial lining fluid concentrations, which may correlate with improved efficacy in the treatment of nosocomial pneumonia. However, clinical superiority has not been demonstrated.


To test the hypothesis that linezolid may be superior to glycopeptides.


Prospective randomized trials that tested linezolid vs. vancomycin or teicoplanin for treatment of nosocomial pneumonia were included. Heterogeneity was analyzed by I(2) and Q statistics. Meta-analysis relative risks were based on fixed and random-effects models. Outcomes evaluated consisted of clinical cure, microbiological eradication, and side effects.


Nine linezolid trials (vancomycin [7]; teicoplanin [2]) were included (n = 2329). The linezolid vs. glycopeptide analysis shows clinical cure relative risk of 1.01 (95% confidence interval, 0.93-1.10; p = .83; I(2) = 0%) and microbiological eradication relative risk of 1.10 (95% confidence interval, 0.98 -1.22; p = .10; I(2) = 0%). Methicillin-resistant Staphylococcus aureus subgroup analysis yielded a microbiological eradication relative risk of 1.10 (95% confidence interval, 0.87-1.38; p = .44; I(2) = 16%). If linezolid is compared with vancomycin only, then clinical cure relative risk is 1.00 (95% confidence interval, 0.90-1.12), microbiological eradication and methicillin-resistant Staphylococcus aureus relative risks are 1.07 (95% confidence interval, 0.90-1.26; p = .45) and 1.05 (95% confidence interval, 0.82-1.33; p = .71). The risks of thrombocytopenia (relative risk, 1.93; 95% confidence interval, 1.30-2.87; p = .001) and gastrointestinal events (relative risk, 2.02; 95% confidence interval, 1.10-3.70; p = .02) are higher with linezolid, but no differences are seen for renal dysfunction (relative risk, 0.89; 95% confidence interval, 0.56-1.43; p = .64) or all-cause mortality (relative risk, 0.95; 95% confidence interval, 0.76-1.18; p = .63).


Our study does not demonstrate clinical superiority of linezolid vs. glycopeptides for the treatment of nosocomial pneumonia despite a statistical power of 95%. Linezolid shows a significant two-fold increase in the risk of thrombocytopenia and gastrointestinal events. Vancomycin and teicoplanin are not associated with more renal dysfunction than linezolid.



March 24, 2018 at 10:56 am

Treatment of hospital-acquired pneumonia with linezolid or vancomycin: a systematic review and meta-analysis.

BMJ Open. 2013 Oct 14;3(10):e003912.

Kalil AC1, Klompas M, Haynatzki G, Rupp ME.

Author information

1 Infectious Diseases Division, Internal Medicine Department, University of Nebraska Medical Center, Omaha, Nebraska, USA.



Hospital-acquired pneumonia remains the most lethal and expensive nosocomial infection worldwide. Optimal therapy remains controversial. We aimed to compare mortality and clinical response outcomes in patients treated with either linezolid or vancomycin.


Systematic review and meta-analysis.


PubMed, EMBASE, Cochrane Library, American College of Physicians Journal Club, Evidence-based Medicine BMJ and abstracts from infectious diseases and critical care meetings were searched through April 2013.


All randomised clinical trials comparing linezolid to vancomycin for hospital-acquired pneumonia.


Preferred reporting items for systematic reviews and meta-analyses guidelines were followed. One author extracted the data and two authors rechecked and verified all data.


Nine randomised trials with a total of 4026 patients were included. The adjusted absolute mortality risk difference (RD) between linezolid and vancomycin was 0.01% (95% CI -2.1% to 2.1%; p=0.992; I(2)=13.5%. The adjusted absolute clinical response difference was 0.9% (95% CI -1.2% to 3.1%; p=0.409; I(2)=0%. The risk of both microbiological (RD=5.6%, 95% CI -2.2% to 13.3%; p=0.159; I(2)=0%) and methicillin-resistant Staphylococcus aureus (RD=6.4%, 95% CI -4.1% to 16.9%; p=0.230; I(2)=0%) eradication were not different between linezolid and vancomycin. Gastrointestinal side effects were more frequent with linezolid (RD=0.8% (95% CI 0% to 1.5%; p=0.05), but no differences were found with renal failure, thrombocytopenia and drug discontinuation due to adverse events. Our sample size provided 99.9% statistical power to detect differences between drugs regarding clinical response and mortality.


Linezolid and vancomycin have similar efficacy and safety profiles. The high statistical power and the near-zero efficacy difference between both antibiotics demonstrates that no drug is superior for the treatment of hospital-acquired pneumonia.


March 21, 2018 at 9:28 am

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