Review – Role of cephalosporins in the era of Clostridium difficile infection

Journal of Antimicrobial & Chemotherapy January 1, 2017 V.72 N.1 P.1-18

Mark H. Wilcox, James D. Chalmers, Carl E. Nord, Jane Freeman, and Emilio Bouza

1Leeds Institute of Biomedical and Clinical Sciences, Faculty of Medicine and Health, University of Leeds, and Microbiology, Leeds Teaching Hospitals, Leeds, UK

2Tayside Respiratory Research Group, University of Dundee, Dundee, UK

3Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden

4Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain

The incidence of Clostridium difficile infection (CDI) in Europe has increased markedly since 2000. Previous meta-analyses have suggested a strong association between cephalosporin use and CDI, and many national programmes on CDI control have focused on reducing cephalosporin usage. Despite reductions in cephalosporin use, however, rates of CDI have continued to rise.

This review examines the potential association of CDI with cephalosporins, and considers other factors that influence CDI risk. EUCLID (the EUropean, multicentre, prospective biannual point prevalence study of CLostridium difficile Infection in hospitalized patients with Diarrhoea) reported an increase in the annual incidence of CDI from 6.6 to 7.3 cases per 10 000 patient bed-days from 2011–12 to 2012–13, respectively.

While CDI incidence and cephalosporin usage varied widely across countries studied, there was no clear association between overall cephalosporin prescribing (or the use of any particular cephalosporin) and CDI incidence.

Moreover, variations in the pharmacokinetic and pharmacodynamic properties of cephalosporins of the same generation make categorization by generation insufficient for predicting impact on gut microbiota. A multitude of additional factors can affect the risk of CDI.

Antibiotic choice is an important consideration; however, CDI risk is associated with a range of antibiotic classes. Prescription of multiple antibiotics and a long duration of treatment are key risk factors for CDI, and risk also differs across patient populations.

We propose that all of these are factors that should be taken into account when selecting an antibiotic, rather than focusing on the exclusion of individual drug classes.

PDF

http://jac.oxfordjournals.org/content/72/1/1.full.pdf+html

Distribution of Fatal Vibrio Vulnificus Necrotizing Skin and Soft-Tissue Infections: A Systematic Review and Meta-Analysis.

Medicine (Baltimore). 2016 Feb;95(5):e2627.

Huang KC1, Weng HH, Yang TY, Chang TS, Huang TW, Lee MS.

Author information

1 From the College of Medicine, Chang Gung University, Taoyuan (K-CH, H-HW, T-SC, T-WH, MSL); Department of Orthopaedic Surgery (K-CH, T-YY, T-WH); Department of Diagnostic Radiology (H-HW); Department of Gastroenterology, Chang Gung Memorial Hospital, Chaiyi (T-SC); and Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Kaohsiung, Taiwan (MSL).

Abstract

Vibrio vulnificus necrotizing skin and soft tissue infections (VNSSTIs), which have increased significantly over the past few decades, are still highly lethal and disabling diseases despite advancing antibiotic and infection control practices. We, therefore, examined the spatiotemporal distribution of worldwide reported episodes and associated mortality rates of VNSSTIs between 1966 and 2014. The PubMed and Cochrane Library databases were systematically searched for observational studies on patients with VNSSTIs. The primary outcome was all-cause mortality. We did random-effects meta-analysis to obtain estimates for primary outcomes; the estimates are presented as means plus a 95% confidence interval (CI). Data from the selected studies were also extracted and pooled for correlation analyses.Nineteen studies of 2227 total patients with VNSSTIs were analyzed. More than 95% of the episodes occurred in the subtropical western Pacific and Atlantic coastal regions of the northern hemisphere. While the number of cases and the number of deaths were not correlated with the study period (rs = 0.476 and 0.310, P = 0.233 and 0.456, respectively), the 5-year mortality rate was significantly negatively correlated with them (rs = -0.905, P = 0.002). Even so, the pooled estimate of total mortality rates from the random-effects meta-analysis was as high as 37.2% (95% CI: 0.265-0.479).These data suggest that VNSSTIs are always an important public health problem and will become more critical and urgent because of global warming. Knowing the current distribution of VNSSTIs will help focus education, policy measures, early clinical diagnosis, and appropriate medical and surgical treatment for them.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748892/pdf/medi-95-e2627.pdf

Clinical features and treatment of patients with Vibrio vulnificus infection

Int J Infect Dis. 2017 Jun;59:1-6.

Yu W1, Shen X1, Pan H2, Xiao T1, Shen P1, Xiao Y3.

Author information

1 State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

2 Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Hangzhou, China.

3 State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Electronic address: xiao-yonghong@163.com

Abstract

OBJECTIVES:

Infections with Vibrio vulnificus are commonly fatal, and the speed and accuracy of diagnosis and treatment is directly linked to mortality. The main aims of this study were to investigate the clinical characteristics of six patients with V. vulnificus infections retrospectively and to determine the effect of treatment with tigecycline (TGC) alone compared with doxycycline plus ceftazidime (DOX/CAZ).

METHODS:

The medical records of patients were reviewed. The species-specific and pathogenic gene markers were detected by PCR, and multilocus sequence typing (MLST) was performed. Furthermore, the effects of TGC and of DOX/CAZ were determined using time-kill assays.

RESULTS:

MLST revealed six different sequence types and five of them were novel. The complete clinical pattern (vcg type C, CPS operon allele 1, 16S-rRNA type B) was found in one strain and the others had a mixed pattern. The lesion was mainly located at the distal end of the extremities and the most common clinical symptoms were fever, pain, erythema, and local swelling. The in vitro time-kill assay indicated that TGC monotherapy at a concentration of 0.1mg/l had a rapid bactericidal effect against the six tested V. vulnificus strains at 24h.

CONCLUSIONS:

TGC alone might be a better potential therapeutic option than the traditional combination of DOX/CAZ against V. vulnificus.

PDF

http://www.ijidonline.com/article/S1201-9712(17)30101-7/pdf

Moraxella osloensis peritonitis : Case report and review.

Rev Esp Quimioter. 2016 Jun;29(3):161-3.

[Article in Spanish]

Hernández-Egido S1, Puerta-Mateo A, Cores-Calvo O, Ruiz-Ferraras E.

Author information

1 Sara Hernández Egido, Complejo Asistencial Universitario de Salamanca Paseo de San Vicente nº 58-182 C.P. 37007 Salamanca, Spain. sathassa@hotmail.com.

PDF

http://seq.es/seq/0214-3429/29/3/hernandez26mar2016.pdf

Systematic Review and Meta-Analysis of the Efficacy and Safety of Telavancin for Treatment of Infectious Disease: Are We Clearer?

Front Pharmacol. 2016 Sep 23;7:330. eCollection 2016.

Chuan J1, Zhang Y1, He X1, Zhu Y1, Zhong L1, Yu D1, Xiao H1.

Author information

1 Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China Chengdu, China.

Abstract

Objective: Telavancin is approved to treat complicated skin and skin structure infections, hospital-acquired, and ventilator-associated bacterial pneumonia caused by Staphylococcus aureus. A previous meta-analysis of randomized controlled trials suggested that it might be an alternative to vancomycin in cases of difficult-to-treat meticillin-resistant S. aureus infections. We did a meta-analysis including one new trial to access the efficacy and safety of telavancin.

Methods: We searched PubMed, Cochrane Central Register of Controlled Trials, EMBASE and ClinicalTrials.gov up to December 30, 2015 to identify randomized controlled trials that assessed the clinical efficacy, eradication efficiency, adverse events and laboratory abnormalities of telavancin vs. other antibiotic agents for bacterial infection. Meta-analysis was performed using Review Manager 5.3.0.

Results: Five studies (3790 participants) were included in the meta-analysis. There was no significant difference in treatment success with telavancin than with control antibiotic agents. The pooled pathogen eradication for the telavancin group was numerically higher than that for the control groups, but there was no significant difference. While all-cause mortalities and serious adverse events were comparable between telavancin and control antibiotic agents, adverse event-related withdrawals (OR 1.47, 95% CI 1.13-1.91) were higher in telavancin group. The total number adverse events were more in the telavancin group than in the control groups, especially in the digestive system (OR 1.57, 95% CI 1.37-1.79), nervous system (OR 2.14, 95% CI 1.86-2.47) and urogenital system (OR 2.54, 95% CI 1.99-3.25). Serum creatinine increase (OR 2.25, 95% Cl 1.78-2.85) and hypokalemia (OR 1.74, 95% CI 1.19-2.53) occurred more frequently in telavancin group compared to control groups.

Conclusion: Telavancin may be as effective as but no better than the comparison therapy for S. aureus infection. However, because of the high risk of adverse event-related withdrawals and potential nephrotoxicity, prudence with the clinical use of telavancin in infections is required.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033967/pdf/fphar-07-00330.pdf

Current and Future Considerations for the Treatment of Hospital-Acquired Pneumonia.

Adv Ther. 2016 Feb;33(2):151-66.

Montravers P1,2, Harpan A3, Guivarch E3,4.

Author information

1 Département d’Anesthésie-Réanimation, CHU Bichat Claude-Bernard-HUPNVS, Assistance Publique-Hôpitaux de Paris, University Denis Diderot, PRESS Sorbonne Cité, 46 Rue Henri-Huchard, 75018, Paris, France. philippe.montravers@aphp.fr

2 University Denis Diderot, PRESS Sorbonne Cité, Paris, France. philippe.montravers@aphp.fr

3 Département d’Anesthésie-Réanimation, CHU Bichat Claude-Bernard-HUPNVS, Assistance Publique-Hôpitaux de Paris, University Denis Diderot, PRESS Sorbonne Cité, 46 Rue Henri-Huchard, 75018, Paris, France.

4 University Denis Diderot, PRESS Sorbonne Cité, Paris, France.

Abstract

Hospital-acquired pneumonia (HAP) and health-care-associated pneumonia (HCAP) are leading causes of death, morbidity, and resource utilization in hospitalized patients, and are associated with a broad range of Gram-positive and Gram-negative pathogens.

Here, we discuss the different definitions of HAP and HCAP, review current guidelines regarding the treatment of these conditions, highlight the shortcomings of current therapeutic options, and discuss new antibiotic treatments.

To optimize therapeutic outcomes in patients with HAP/HCAP, initial antimicrobial treatment must be appropriate and should be given as soon as possible; inappropriate or delayed therapy greatly increases morbidity and mortality.

Selection of the most appropriate antimicrobial agent depends on the causative pathogen(s); initial broad-spectrum therapy is commonly recommended and should cover all pathogens that may be present.

Treatment selection should also take into consideration the following factors: knowledge of underlying local risk factors for antimicrobial resistance, disease staging, and risk factors related to specific pathogens such as Pseudomonas aeruginosa, Acinetobacter spp., and methicillin-resistant Staphylococcus aureus (MRSA).

Guidelines consistently emphasize the importance of treating HAP and HCAP with early and appropriate broad-spectrum antibiotics, and recent developments in this field have resulted in the availability of several additional treatment options.

Telavancin shows potent activity against Gram-positive bacteria including MRSA and can be administered once daily; it was approved in the USA and European Union for the treatment of HAP after demonstrating non-inferiority to vancomycin.

Ceftobiprole medocaril exhibits rapid antimicrobial activity against a broad range of both Gram-positive and Gram-negative pathogens, including MRSA.

It was approved for the treatment of HAP (excluding ventilator-associated pneumonia) and community-acquired pneumonia in Europe in 2013.

These new treatments may offer effective alternative therapeutic options for the management of HAP.

FUNDING:

Basilea Pharmaceutica Ltd., Basel, Switzerland.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769724/pdf/12325_2016_Article_293.pdf

Guidelines for the prevention of intravascular catheter-related infections. Centers for Disease Control and Prevention.

MMWR Recomm Rep. 2002 Aug 9;51(RR-10):1-29.

O’Grady NP1, Alexander M, Dellinger EP, Gerberding JL, Heard SO, Maki DG, Masur H, McCormick RD, Mermel LA, Pearson ML, Raad II, Randolph A, Weinstein RA.

Author information

1 National Institutes of Health, Bethesda, Maryland, USA.

Abstract

These guidelines have been developed for practitioners who insert catheters and for persons responsible for surveillance and control of infections in hospital, outpatient, and home health-care settings.

This report was prepared by a working group comprising members from professional organizations representing the disciplines of critical care medicine, infectious diseases, health-care infection control, surgery anesthesiology interventional radiology pulmonary medicine, pediatric medicine, and nursing.

The working group was led by the Society of Critical Care Medicine (SCCM), in collaboration with the Infectious Disease Society of America (IDSA), Society for Healthcare Epidemiology ofAmerica (SHEA), Surgical Infection Society (SIS), American College of Chest Physicians (ACCP), American Thoracic Society (ATS), American Society of Critical Care Anesthesiologists (ASCCA), Association for Professionals in Infection Control and Epidemiology (APIC), Infusion Nurses Society (INS), Oncology Nursing Society (ONS), Society of Cardiovascular and Interventional Radiology (SCVIR), American Academy of Pediatrics (AAP), and the Healthcare Infection Control Practices Advisory Committee (HICPAC) of the Centers for Disease Control and Prevention (CDC) and is intended to replace the Guideline for Prevention of Intravascular Device-Related Infections published in 1996 These guidelines are intended to provide evidence-based recommendations for preventing catheter-related infections.

Major areas of emphasis include

1) educating and training health-care providers who insert and maintain catheters;

2) using maximal sterile barrier precautions during central venous catheter insertion;

3) using a 2% chlorhexidine preparation for skin antisepsis;

4) avoiding routine replacement of central venous catheters as a strategy to prevent infection; and

5) using antiseptic/antibiotic impregnated short-term central venous catheters if the rate of infection is high despite adherence to other strategies (i.e., education and training, maximal sterile barrier precautions, and 2% chlorhexidine for skin antisepsis).

These guidelines also identify performance indicators that can be used locally by health-care institutions or organizations to monitor their success in implementing these evidence-based recommendations.

PDF

https://www.cdc.gov/mmwr/PDF/rr/rr5110.pdf

ERRATUM

https://www.cdc.gov/mmwr/PDF/wk/mm5132.pdf