Evolution and dissemination of the Klebsiella pneumoniae clonal group 258 throughout Israeli post-acute care hospitals, 2008–13

Journal of Antimicrobial Chemotherapy August 2017 V.72 N.8 P.2219–2224

EDITOR’S CHOICE

Amos Adler; Ziv Lifshitz; Michal Gordon; Debbie Ben-David; Efrat Khabra

Objectives

The KPC-producing Klebsiella pneumoniae (KPC-KP) clonal group (CG) 258 has disseminated throughout Israeli post-acute care hospitals (PACHs). The objectives of the study were (i) to describe the evolution and (ii) to understand the dissemination modes of CG 258 in the PACH system in Israel.

Methods

KPC-KP surveillance cultures isolates were collected in Israeli PACHs in three national point-prevalence surveys: 2008, 2011 and 2013. CG 258 was identified by pilv-l PCR. WGS was performed for CG 258 isolates from 9 of 14 PACHs and data extracted for core-genome MLST (cgMLST) and for capsule polysaccharide gene cluster analysis.

Results

The proportional representation of CG 258 among the KPC-KP isolates increased from 72 of 104 isolates (69.2%) in 2008 to 113 of 133 isolates (85%) in 2011 (P = 0.004 for 2008 versus 2011) and remained high in 2013 [56 of 67 isolates (83.6%)]. All isolates were related to CG 258 clade 2. cgMLST phylogenetic analysis showed relative convergence in the 2008 survey, with increasing diversification in the subsequent surveys. A predominantly institutional dissemination pattern was observed only in centre F from southern Israel. A predominantly regional dissemination pattern was observed in the two PACHs in Jerusalem. The other PACHs were characterized by a combined institutional and generalized pattern, with the majority of isolates clustering within the same PACH and survey.

Conclusions

CG 258 clade 2 has retained its predominance despite increased diversification. Although interchanging of CG 258 strains occurred between most PACHs, local spread is the leading cause of its dissemination.

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August 11, 2017 at 9:17 am

Global epidemiology of CTX-M β-lactamases: temporal and geographical shifts in genotype

Journal of Antimicrobial Chemotherapy August 2017 V.72 N.8 P.2145–2155

EDITOR’S CHOICE

Edward R. Bevan; Annie M. Jones; Peter M. Hawkey

Globally, rates of ESBL-producing Enterobacteriaceae are rising. We undertook a literature review, and present the temporal trends in blaCTX-M epidemiology, showing that blaCTX-M-15 and blaCTX-M-14 have displaced other genotypes in many parts of the world.

Explanations for these changes can be attributed to:

(i) horizontal gene transfer (HGT) of plasmids;

(ii) successful Escherichia coli clones;

(iii) ESBLs in food animals;

(iv) the natural environment; and

(v) human migration and access to basic sanitation.

We also provide explanations for the changing epidemiology of blaCTX-M-2 and blaCTX-M-27.

Modifiable anthropogenic factors, such as poor access to basic sanitary facilities, encourage the spread of blaCTX-M and other antimicrobial resistance (AMR) genes, such as blaNDM, blaKPC and mcr-1.

We provide further justification for novel preventative and interventional strategies to reduce transmission of these AMR genes.

PDF

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August 11, 2017 at 9:13 am

Efficacy of anidulafungin in 539 patients with invasive candidiasis: a patient-level pooled analysis of six clinical trials

Journal of Antimicrobial Chemotherapy August 2017 V.72 N.8 P.2368–2377

Bart Jan Kullberg; José Vasquez; Piroon Mootsikapun; Marcio Nucci; José-Artur Paiva …

Objectives

To evaluate the efficacy of anidulafungin for the treatment of candidaemia and invasive candidiasis in a large dataset, including patients with deep-seated tissue candidiasis, neutropenia and infection due to non-albicans Candida species.

Methods

Data were pooled from six prospective, multicentre, multinational studies: four open-label, non-comparative studies of anidulafungin and two double-blind, double-dummy, randomized studies of anidulafungin versus caspofungin (clinical trial registrations: NCT00496197, NCT00548262, NCT00537329, NCT00689338, NCT00806351 and NCT00805740; ClinicalTrials.gov). In all studies, patients with culture-confirmed invasive candidiasis received a single intravenous (iv) loading dose of anidulafungin 200 mg on day 1, followed by 100 mg once-daily. Switch to oral fluconazole or voriconazole was permitted after 5–10 days of iv treatment in all studies except one. Antifungal treatment (iv plus oral therapy if applicable) was maintained for ≥14 days after the last positive Candida culture. The primary endpoint was successful global response at end of iv therapy (EOivT) in the modified ITT (mITT) population.

Results

In total, 539 patients were included (mITT population). The most common baseline Candida species were Candida albicans (47.9%), Candida glabrata (21.0%), Candida tropicalis (13.7%), Candida parapsilosis (13.2%) and Candida krusei (3.5%). Median duration of anidulafungin iv treatment was 10.0 days. The global response success rate at EOivT was 76.4% (95% CI 72.9%–80.0%). All-cause mortality was 13.0% on day 14 and 19.1% on day 28. Adverse events (AEs) were consistent with the known AE profile for anidulafungin.

Conclusions

These data demonstrate that anidulafungin is effective for treatment of candidaemia and invasive candidiasis in a broad patient population.

PDF

https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/jac/72/8/10.1093_jac_dkx116/1/dkx116.pdf?Expires=1502546596&Signature=Mg2uM36lH-8nSWnYuT4WYbUGBOTc4ofTGhDEgaygmz475z1wnBF9V2Y1Wewe52fMW7QyxzzWNh5HoLiQ7fcxlToVF7RDaLUWhXq~wiA39hRQiZfZjLnkI9c~0pN~jOy34zNuSMfYUqbxqiqiRJxfY5TX0psBD4LPIX1Ol7ZFzW9LZfIcFftCGe0WlNtHD12hpVApZApaBuvbMRrevdlU-cc8sx66P9hsL99JQyxw34sHRNEEibg4OOpMENZ6fW-QVB~6WjxClzJcL9QBObYLKe11e2Pqxb~Mk9d1YQAqOZjz3~XCG2iTfR~Kz1pl3HfpQX5XLV9NW2p4iHnNf8zRnw__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q

August 11, 2017 at 9:11 am

Enhanced prophylaxis plus antiretroviral therapy for advanced HIV infection in Africa

N Engl J Med July 20, 2017 V.377 P.233-245.

James Hakim, F.R.C.P., Victor Musiime, Ph.D., Alex J. Szubert, M.Sc., Jane Mallewa, M.D., Abraham Siika, M.Med., Clara Agutu, M.B., Ch.B., M.P.H., Simon Walker, M.Sc., Sarah L. Pett, Ph.D., Mutsa Bwakura-Dangarembizi, M.Med., Abbas Lugemwa, M.D., Symon Kaunda, M.B., Ch.B., Mercy Karoney, M.Sc., Godfrey Musoro, M.Sc., Sheila Kabahenda, M.B., Ch.B., Kusum Nathoo, M.B., Ch.B., Kathryn Maitland, Ph.D., Anna Griffiths, Ph.D., Margaret J. Thomason, Ph.D., Cissy Kityo, M.Sc., Peter Mugyenyi, Ph.D., Andrew J. Prendergast, D.Phil., A. Sarah Walker, Ph.D., and Diana M. Gibb, M.D., for the REALITY Trial Team*

BACKGROUND

In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%.

METHODS

In this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi, and Kenya, we enrolled HIV-infected adults and children 5 years of age or older who had not received previous ART and were starting ART with a CD4+ count of fewer than 100 cells per cubic millimeter. They underwent simultaneous randomization to receive enhanced antimicrobial prophylaxis or standard prophylaxis, adjunctive raltegravir or no raltegravir, and supplementary food or no supplementary food. Here, we report on the effects of enhanced antimicrobial prophylaxis, which consisted of continuous trimethoprim–sulfamethoxazole plus at least 12 weeks of isoniazid–pyridoxine (coformulated with trimethoprim–sulfamethoxazole in a single fixed-dose combination tablet), 12 weeks of fluconazole, 5 days of azithromycin, and a single dose of albendazole, as compared with standard prophylaxis (trimethoprim–sulfamethoxazole alone). The primary end point was 24-week mortality.

RESULTS

A total of 1805 patients (1733 adults and 72 children or adolescents) underwent randomization to receive either enhanced prophylaxis (906 patients) or standard prophylaxis (899 patients) and were followed for 48 weeks (loss to follow-up, 3.1%). The median baseline CD4+ count was 37 cells per cubic millimeter, but 854 patients (47.3%) were asymptomatic or mildly symptomatic. In the Kaplan–Meier analysis at 24 weeks, the rate of death with enhanced prophylaxis was lower than that with standard prophylaxis (80 patients [8.9% vs. 108 [12.2%]; hazard ratio, 0.73; 95% confidence interval [CI], 0.55 to 0.98; P=0.03); 98 patients (11.0%) and 127 (14.4%), respectively, had died by 48 weeks (hazard ratio, 0.76; 95% CI, 0.58 to 0.99; P=0.04). Patients in the enhanced-prophylaxis group had significantly lower rates of tuberculosis (P=0.02), cryptococcal infection (P=0.01), oral or esophageal candidiasis (P=0.02), death of unknown cause (P=0.03), and new hospitalization (P=0.03). However, there was no significant between-group difference in the rate of severe bacterial infection (P=0.32). There were nonsignificantly lower rates of serious adverse events and grade 4 adverse events in the enhanced-prophylaxis group (P=0.08 and P=0.09, respectively). Rates of HIV viral suppression and adherence to ART were similar in the two groups.

CONCLUSIONS

Among HIV-infected patients with advanced immunosuppression, enhanced antimicrobial prophylaxis combined with ART resulted in reduced rates of death at both 24 weeks and 48 weeks without compromising viral suppression or increasing toxic effects. (Funded by the Medical Research Council and others; REALITY Current Controlled Trials number, ISRCTN43622374.)

abstract

http://www.nejm.org/doi/10.1056/NEJMoa1615822

PDF

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1615822

 

N Engl J Med  July 20, 2017 V.377 P.283-284

EDITORIAL – The enduring challenge of advanced HIV infection.

Nathan Ford, M.P.H., Ph.D., and Meg Doherty, M.D., Ph.D.

Until recently, progress in the fight against human immunodeficiency virus (HIV) infection was primarily measured in terms of the number of patients who were started on antiretroviral therapy (ART). Major efforts to increase access to ART in the low- and middle-income countries that are most affected by HIV infection began in 2000, and over the following 15 years, an estimated 8 million HIV-related deaths were averted. In countries with a high burden of disease, this decline translated into important increases in life expectancy.1

Notwithstanding these gains, the decrease in HIV-associated deaths appears to have plateaued in recent years. HIV still causes more than 1 million deaths per year worldwide and remains a leading cause of death and complications in sub-Saharan Africa.1 A key explanation for this enduring high mortality is that despite an evolution toward offering treatment earlier in the course of the disease,2 HIV continues to be identified in a substantial number of patients with advanced infection (which is defined by the World Health Organization [WHO] as a CD4+ count of fewer than 200 cells per cubic millimeter). A recent study of trends across 55 countries showed that more than a third (37%) of the patients who initiated ART in 2015 already had advanced HIV infection.3 Such patients are at high risk for death, even after starting ART (which can increase the inflammatory response), and the risk increases with a decreasing CD4+ count.3 A worrisome new trend that has been observed in countries with long-standing HIV treatment programs is an increase in the number of patients who present for care with advanced HIV infection after a period of treatment interruption…..

abstract

http://www.nejm.org/doi/10.1056/NEJMe1707598

PDF

http://www.nejm.org/doi/pdf/10.1056/NEJMe1707598

 

August 11, 2017 at 8:27 am

Finegoldia magna: a forgotten pathogen in prosthetic joint infection rediscovered by molecular biology.

Clin Infect Dis. 2009 Oct 15;49(8):1244-7.

Levy PY1, Fenollar F, Stein A, Borrione F, Raoult D.

Author information

1 Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes-Unité Mixte de Recherche, Centre National de la Recherche Scientifique 6236-Institut de Recherche et Developpement 198, Faculté de Médecine, Université de la Méditerranée, Marseille, France.

Abstract

In this study, we describe 13 patients with prosthetic infections due to Finegoldia magna (2% of our tested series).

Patients presented with either polymicrobial infection after an open fracture or nosocomial infection after recent prosthesis implantation.

Molecular techniques are critical for diagnosis, and recommended antibiotic prophylaxis has poor activity against F. magna.

PDF

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August 10, 2017 at 3:42 pm

A Case of Septic Arthritis of the Wrist due to Finegoldia magna.

Case Rep Infect Dis. 2014;2014:793053.

Arsene C1, Saste A2, Somiah M1, Mestrovich J1, Berger G1.

Author information

1 Department of Medicine, Sinai-Grace Hospital, Detroit Medical Center/Wayne State School of Medicine, 4th Floor, 6071 West Outer Drive, Detroit, MI 48235, USA.

2 Department of Emergency Medicine, Detroit Receiving Hospital/Detroit Medical Center, 4201 Street Antoine, Suite 3R, Detroit, MI 48201, USA.

Abstract

Finegoldia magna (F. magna) has been described as one of the most frequent pathogens in the etiology of postoperative and prosthetic implant associated septic arthritis.

In this report, we document our first experience with septic arthritis of the wrist caused by F. magna occurring in a joint with primary disease from prior trauma

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005078/pdf/CRIID2014-793053.pdf

August 10, 2017 at 3:41 pm

Risk of surgical site infection, acute kidney injury, and Clostridium difficile infection following antibiotic prophylaxis with vancomycin plus a beta-lactam versus either drug alone: A national propensity-score-adjusted retrospective cohort study.

PLoS Med. 2017 Jul 10;14(7):e1002340.

Branch-Elliman W1,2,3, Ripollone JE4, O’Brien WJ3, Itani KMF2,5,6, Schweizer ML7,8, Perencevich E7,8, Strymish J1,2, Gupta K1,3,5.

Author information

1 Department of Medicine, VA Boston Healthcare System, West Roxbury, Massachusetts, United States of America.

2 Harvard Medical School, Boston, Massachusetts, United States of America.

3 VA Center for Healthcare Organization and Implementation Research, VA Boston Healthcare System, West Roxbury, Massachusetts, United States of America.

4 Boston University School of Public Health, Boston, Massachusetts, United States of America.

5 Boston University School of Medicine, Boston, Massachusetts, United States of America.

6 Department of Surgery, VA Boston Healthcare System, West Roxbury, Massachusetts, United States of America.

7 VA Comprehensive Access & Delivery Research & Evaluation, Iowa City VA Health Care System, Iowa City, Iowa, United States of America.

8 Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.

Abstract

BACKGROUND:

The optimal regimen for perioperative antimicrobial prophylaxis is controversial. Use of combination prophylaxis with a beta-lactam plus vancomycin is increasing; however, the relative risks and benefits associated with this strategy are unknown. Thus, we sought to compare postoperative outcomes following administration of 2 antimicrobials versus a single agent for the prevention of surgical site infections (SSIs). Potential harms associated with combination regimens, including acute kidney injury (AKI) and Clostridium difficile infection (CDI), were also considered.

METHODS AND FINDINGS:

Using a multicenter, national Veterans Affairs (VA) cohort, all patients who underwent cardiac, orthopedic joint replacement, vascular, colorectal, and hysterectomy procedures during the period from 1 October 2008 to 30 September 2013 and who received planned manual review of perioperative antimicrobial prophylaxis regimen and manual review for the 30-day incidence of SSI were included. Using a propensity-adjusted log-binomial regression model stratified by type of surgical procedure, the association between receipt of 2 antimicrobials (vancomycin plus a beta-lactam) versus either single agent alone (vancomycin or a beta-lactam) and SSI was evaluated. Measures of association were adjusted for age, diabetes, smoking, American Society of Anesthesiologists score, preoperative methicillin-resistant Staphylococcus aureus (MRSA) status, and receipt of mupirocin. The 7-day incidence of postoperative AKI and 90-day incidence of CDI were also measured. In all, 70,101 procedures (52,504 beta-lactam only, 5,089 vancomycin only, and 12,508 combination) with 2,466 (3.5%) SSIs from 109 medical centers were included. Among cardiac surgery patients, combination prophylaxis was associated with a lower incidence of SSI (66/6,953, 0.95%) than single-agent prophylaxis (190/12,834, 1.48%; crude risk ratio [RR] 0.64, 95% CI 0.49, 0.85; adjusted RR 0.61, 95% CI 0.46, 0.83). After adjusting for SSI risk, no association between receipt of combination prophylaxis and SSI was found for the other types of surgeries evaluated, including orthopedic joint replacement procedures. In MRSA-colonized patients undergoing cardiac surgery, SSI occurred in 8/346 (2.3%) patients who received combination prophylaxis versus 4/100 (4.0%) patients who received vancomycin alone (crude RR 0.58, 95% CI 0.18, 1.88). Among MRSA-negative and -unknown cardiac surgery patients, SSIs occurred in 58/6,607 (0.9%) patients receiving combination prophylaxis versus 146/10,215 (1.4%) patients who received a beta-lactam alone (crude RR 0.61, 95% CI 0.45, 0.83). Based on these associations, the number needed to treat to prevent 1 SSI in MRSA-colonized patients is estimated to be 53, compared to 176 in non-MRSA patients. CDI incidence was similar in both exposure groups. Across all types of surgical procedures, risk of AKI was increased in the combination antimicrobial prophylaxis group (2,971/12,508 [23.8%] receiving combination versus 1,058/5,089 [20.8%] receiving vancomycin alone versus 7,314/52,504 [13.9%] receiving beta-lactam alone). We found a significant association between absolute risk of AKI and receipt of combination regimens across all types of procedures. If the observed association is causal, the number needed to harm for severe AKI following cardiac surgery would be 167. The major limitation of our investigation is that it is an observational study in a predominantly male population, which may limit generalizability and lead to unmeasured confounding.

CONCLUSIONS:

There are benefits but also unintended consequences of antimicrobial and infection prevention strategies aimed at “getting to zero” healthcare-associated infections. In our study, combination prophylaxis was associated with both benefits (reduction in SSIs following cardiac surgical procedures) and harms (increase in postoperative AKI). In cardiac surgery patients, the difference in risk-benefit profile by MRSA status suggests that MRSA-screening-directed prophylaxis may optimize benefits while minimizing harms in this selected population. More information about long-term outcomes and patient and societal preferences regarding risk of SSI versus risk of AKI is needed to improve clinical decision-making.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503171/pdf/pmed.1002340.pdf

August 10, 2017 at 8:40 am

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