Posts filed under ‘Resistencia bacteriana’

Trends in antimicrobial resistance in bloodstream infection isolates at a large urban hospital in Malawi (1998–2016): a surveillance study

Lancet Infectious Diseases October 2017 V.17 N.10

Patrick Musicha, MSc, Jennifer E Cornick, PhD, Naor Bar-Zeev, PhD, Prof Neil French, Clemens Masesa, MSc, Brigitte Denis, MSc, Neil Kennedy, MMedSci, Jane Mallewa, MD, Prof Melita A Gordon, MD, Chisomo L Msefula, PhD, Prof Robert S Heyderman, PhD, Dean B Everett, PhD, Dr Nicholas A Feasey, PhD

Background

Bacterial bloodstream infection is a common cause of morbidity and mortality in sub-Saharan Africa, yet few facilities are able to maintain long-term surveillance. The Malawi-Liverpool-Wellcome Trust Clinical Research Programme has done sentinel surveillance of bacteraemia since 1998. We report long-term trends in bloodstream infection and antimicrobial resistance from this surveillance.

Methods

In this surveillance study, we analysed blood cultures that were routinely taken from adult and paediatric patients with fever or suspicion of sepsis admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi from 1998 to 2016. The hospital served an urban population of 920 000 in 2016, with 1000 beds, although occupancy often exceeds capacity. The hospital admits about 10 000 adults and 30 000 children each year. Antimicrobial susceptibility tests were done by the disc diffusion method according to British Society of Antimicrobial Chemotherapy guidelines. We used the Cochran-Armitage test for trend to examine trends in rates of antimicrobial resistance, and negative binomial regression to examine trends in icidence of bloodstream infection over time.

Findings

Between Jan 1, 1998, and Dec 31, 2016, we isolated 29 183 pathogens from 194 539 blood cultures. Pathogen detection decreased significantly from 327·1/100 000 in 1998 to 120·2/100 000 in 2016 (p<0·0001). 13 366 (51·1%) of 26 174 bacterial isolates were resistant to the Malawian first-line antibiotics amoxicillin or penicillin, chloramphenicol, and co-trimoxazole; 68·3% of Gram-negative and 6·6% of Gram-positive pathogens. The proportions of non-Salmonella Enterobacteriaceae with extended spectrum beta-lactamase (ESBL) or fluoroquinolone resistance rose significantly after 2003 to 61·9% in 2016 (p<0·0001). Between 2003 and 2016, ESBL resistance rose from 0·7% to 30·3% in Escherichia coli, from 11·8% to 90·5% in Klebsiella spp and from 30·4% to 71·9% in other Enterobacteriaceae. Similarly, resistance to ciprofloxacin rose from 2·5% to 31·1% in E coli, from 1·7% to 70·2% in Klebsiella spp and from 5·9% to 68·8% in other Enterobacteriaceae. By contrast, more than 92·0% of common Gram-positive pathogens remain susceptible to either penicillin or chloramphenicol. Meticillin-resistant Staphylococcus aureus (MRSA) was first reported in 1998 at 7·7% and represented 18·4% of S aureus isolates in 2016.

Interpretation

The rapid expansion of ESBL and fluoroquinolone resistance among common Gram-negative pathogens, and the emergence of MRSA, highlight the growing challenge of bloodstream infections that are effectively impossible to treat in this resource-limited setting.

Funding

Wellcome Trust, H3ABionet, Southern Africa Consortium for Research Excellence (SACORE).

PDF

http://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(17)30394-8.pdf

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September 24, 2017 at 11:00 am

Patterns of bacteraemia aetiology

Lancet Infectious Diseases October 2017 V.17 N.10

COMMENT

Alan Cross, Myron M Levine

Bloodstream infections are a leading cause of morbidity and mortality in both high-income and lower-income countries, but the causative organisms and risk factors differ. Human beings coexist with diverse bacterial flora on their skin and their nasal, pharyngeal, and gastrointestinal mucosae. Physical barriers and non-specific immune defences keep these bacteria in check.

However, various primary pathogens can invade via the respiratory mucosa (eg, some Streptococcus pneumoniae serotypes) or gastrointestinal (Salmonella Typhi) mucosa or integument (Staphylococcus aureus), then enter the bloodstream and provoke clinical syndromes such as sepsis, febrile bacteraemia, meningitis, or enteric fever…..

PDF

http://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(17)30491-7.pdf

September 24, 2017 at 10:58 am

Pitfalls of defining combination therapy for carbapenem-resistant Enterobacteriaceae in observational studies

European Journal of Clinical Microbiology & Infectious Diseases. V.36 N.10 P.1707–1709

Editorial         

R. Giacobbe A. E. MaraoloC. Viscoli

ISGRI-SITA (Italian Study Group on Resistant Infections of the Società Italiana Terapia Antinfettiva)

Carbapenem-resistant Enterobacteriaceae (CRE) are now endemic in several countries [1]. Infections caused by these organisms are associated with high mortality, with the frequently multidrug-resistant phenotype of CRE being deemed as one of the major culprits [2, 3]. Indeed, clinicians have usually little choice but to use antibiotics with reduced activity; sometimes they do not have any active choice at all. Many clinicians, including ourselves, have therefore started to administer combinations of antimicrobials, mainly with the aim of taking advantage of possible additive or synergistic effects …

PDF

https://link.springer.com/content/pdf/10.1007%2Fs10096-017-3010-z.pdf

 

September 23, 2017 at 9:59 pm

2017-09 Antibacterial agents in clinical development – An analysis of the antibacterial clinical development pipeline, including tuberculosis. OMS 45 pags

Contents:

Acknowledgements

Abbreviations and acronyms

Executive summary

  1. Introduction
  2. Methods and search results

2.1 Scope and inclusion criteria

2.2 Assessment of activity against priority pathogens and innovativeness

  1. Agents in clinical development

3.1 Antibiotics potentially active against pathogens on the WHO priority  pathogens list

3.2 Combinations without new chemical entities

3.3 Agents in development for treating tuberculosis

3.4 Agents in development for treating Clostridium difficile infections

3.5 Biological agents

3.6 Agents that are not under active development or for which there is no  recent information

  1. Analysis of the clinical pipeline
  2. Outlook and discussion

5.1 The current clinical pipeline is insufficient against pathogens on the  WHO priority pathogens list and TB.

5.2 More innovative approaches are required, but there are scientific  challenges.

5.3 Outlook: More work is required to fill the pipeline.

5.4 Methodological considerations

  1. References

Annex 1. Search strategy and results

Annex 2. Declarations of interests of advisory group members

PDF

http://apps.who.int/iris/bitstream/10665/258965/1/WHO-EMP-IAU-2017.11-eng.pdf

 

September 22, 2017 at 8:03 am

Comparison Between Carbapenems and β-Lactam/β-Lactamase Inhibitors in the Treatment for Bloodstream Infections Caused by Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae: A Systematic Review and Meta-Analysis

Open Forum Infectious Diseases April 2017 V.4 N.2

Maged Muhammed; Myrto Eleni Flokas; Marios Detsis; Michail Alevizakos; Eleftherios Mylonakis

Background.

Carbapenems are widely used for the management of bloodstream infections (BSIs) caused by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE). However, the wide use of carbapenems has been associated with carbapenem-resistant Enterobacteriaceae development.

Methods.

We searched the PubMed and Scopus databases (last search date was on June 1, 2016) looking for studies that reported mortality in adult patients with ESBL-PE BSIs that were treated with carbapenems or β-lactam/β-lactamase inhibitors (BL/BLIs).

Results.

Fourteen studies reported mortality data in adult patients with ESBL-PE BSI that were treated with carbapenems or BL/BLIs. Among them, 13 studies reported extractable data on empiric therapy, with no statistically significant difference in mortality of patients with ESBL-PE BSI that were treated empirically with carbapenems (22.1%; 121 of 547), compared with those that received empiric BL/BLIs (20.5%; 109 of 531; relative risk [RR], 1.05; 95% confidence interval [CI], 0.83–1.37; I2 = 20.7%; P = .241). In addition, 7 studies reported data on definitive therapy. In total, 767 patients (79.3%) received carbapenems and 199 patients (20.6%) received BL/BLIs as definitive therapy, and there was again no statistically significant difference (RR, 0.62; 95% CI, 0.25–1.52; I2 = 84.6%; P < .001). Regarding specific pathogens, the use of empiric BL/BLIs in patients with BSI due to ESBL-Escherichia coli was not associated with a statistically significant difference in mortality (RR, 1.014; 95% CI, 0.491–2.095; I2 = 62.5%; P = .046), compared with the use of empiric carbapenems.

Conclusions.

These data do not support the wide use of carbapenems as empiric therapy, and BL/BLIs might be effective agents for initial/empiric therapy for patients with BSI caused by likely ESBL-PE, and especially ESBL-E coli.

PDF

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September 3, 2017 at 6:57 pm

Carbapenem-Resistant Enterobacteriaceae Infections: Results From a Retrospective Series and Implications for the Design of Prospective Clinical Trials

Open Forum Infectious Diseases April 2017 V.4 N.2

Elizabeth L. Alexander; Jeffery Loutit; Mario Tumbarello; Richard Wunderink; Tim Felton …

Background.

The increasing incidence of multidrug-resistant Gram negatives, such as carbapenem-resistant Enterobacteriaceae (CRE), has resulted in a critical need for new antimicrobials. Most studies of new antimicrobials have been performed in patients with nondrug-resistant pathogens. We performed a retrospective analysis of patients with CRE infections to inform the design of phase 3 clinical trials.

Methods.

This was a retrospective study at 22 centers in 4 countries. Baseline data, treatment, and outcomes were collected in patients with complicated urinary tract infection (cUTI)/acute pyelonephritis (AP), hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), and bacteremia due to CRE.

Results.

Two hundred fifty-six cases of CRE infection were identified: 75 cUTI/AP, 21 HABP, 20 VABP, and 140 bacteremia. The patient population had significant comorbidities: 32.8% had chronic renal insufficiency, and 26.2% were immunocompromised. Illness severity at presentation was high: 29.3% presented with septic shock. Treatment regimens varied widely; however, a majority of patients received combination therapy. Outcomes were universally poor (28-day mortality was 28.1%) across all sites of infection, particularly in dialysis patients and those with sepsis.

Conclusions.

The CRE infections occured in patients with substantial comorbidities and were associated with high mortality and low rates of clinical cure with available antibiotics. Patients with these comorbidities are often excluded from enrollment in clinical trials for registration of new drugs. These results led to changes in the inclusion/exclusion criteria of a phase 3 trial to better represent the patient population with CRE infections and enable enrollment. Observational studies may become increasingly important to guide clinical trial design, inform on the existing standard of care, and provide an external control for subsequent trials.

PDF

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September 3, 2017 at 6:51 pm

Ceftaroline for Severe Methicillin-Resistant Staphylococcus aureus Infections: A Systematic Review

Open Forum Infectious Diseases April  2017 V.4 N.2

Reese A. Cosimi; Nahal Beik; David W. Kubiak; Jennifer A. Johnson

This article reviews and evaluates the existing literature describing clinical outcomes and safety of ceftaroline in severe methicillin-resistant Staphylococcus aureus infections.

Ceftaroline is approved by the Food and Drug Administration for acute bacterial skin and skin-structure infections and community-acquired bacterial pneumonia, including cases with concurrent bacteremia. Use for serious methicillin-resistant Staphylococcus aureus (MRSA) infections has risen for a multitude of reasons.

The aim of this article is to review the literature evaluating clinical outcomes and safety of ceftaroline prescribed for serious MRSA infections. We conducted a literature search in Ovid (Medline) and PubMed for reputable case reports, clinical trials, and reviews focusing on the use of ceftaroline for treatment of MRSA infections.

Twenty-two manuscripts published between 2010 and 2016 met inclusion criteria. Mean clinical cure was 74% across 379 patients treated with ceftaroline for severe MRSA infections. Toxicities were infrequent. Ceftaroline treatment resulted in clinical and microbiologic cure for severe MRSA infections. Close monitoring of hematological parameters is necessary with prolonged courses of ceftaroline.

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September 3, 2017 at 6:40 pm

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