REVIEW – New agents for the treatment of infections with Gram-negative bacteria: restoring the miracle or false dawn?

Clin Microbiol Infect. October 2017 V.23 N.10 P.704-712.

Wright H1, Bonomo RA2, Paterson DL3.

Abstract

BACKGROUND:

Antibiotic resistance in Gram-negative resistance has developed without a commensurate response in the successful development of antibiotic agents, though recent progress has been made.

AIMS:

This review aims to provide a summary of the existing evidence on efficacy, spectrum of activity and the development of resistance of new agents that have been licensed or have completed advanced clinical trials and that possess activity against resistant Gram-negative organisms.

SOURCES:

A review of the published literature via MEDLINE database was performed. Relevant clinical trials were identified with the aid of the clinicaltrials.gov registry. Further data were ascertained from review of abstracts from recent international meetings and pharmaceutical companies.

CONTENT:

Data on the mechanism of action, microbiological spectrum, clinical efficacy and development of resistance are reported for new agents that have activity against Gram-negative organisms. This includes the β-lactam/β-lactamase inhibitor combinations ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/cilastatin/relebactam, meropenem/vaborbactam and aztreonam/avibactam; cefiderocol, a siderophore cephalosporin; plazomicin and eravacycline.

IMPLICATIONS:

The development of new agents with activity against multidrug-resistant Gram-negative pathogens has provided important therapeutic options for clinicians. Polymyxins appear to have been supplanted by new agents as first-line therapy for Klebsiella pneumoniae carbapenemase producers. Cefiderocol and ceftazidime/avibactam/aztreonam are promising options for metallo-β-lactamase producers, and cefiderocol and ceftolozane/tazobactam for multiply resistant Pseudomonas aeruginosa, but definitive data showing clinical efficacy is as yet lacking. Reports of the development of resistance early after the release and use of new agents is of concern. Orally administered options and agents active effective against Acinetobacter baumannii are under-represented in clinical development.

FULL TEXT

https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(17)30495-0/fulltext

PDF

https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(17)30495-0/pdf

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Antibiotic penetration into bone and joints: An updated review

International Journal of Infectious Diseases April 2019 V.81 N.4 P.128-136

Abrar K. Thabit, Dania F. Fatani, Maryam S. Bamakhrama, Ola A. Barnawi, Lana O. Basudan, Shahad F. Alhejaili

Highlights

• Despite the rigid structure of bone, many antibiotics demonstrated a good penetration profile.
• Diffusion into synovial fluid was exhibited by many antibiotics despite their variation in pharmacokinetic properties.
• Only penicillin, flucloxacillin, and metronidazole showed lower than optimum penetration profiles.
• Antibiotics with good penetration profiles in bone and joints represent potential options for the treatment of osteomyelitis and septic arthritis.

Treatment of bone and joint infections can be challenging as antibiotics should penetrate through the rigid bone structure and into the synovial space. Several pharmacokinetic studies measured the extent of penetration of different antibiotics into bone and joint tissues. This review discusses the results of these studies and compares them with minimum inhibitory concentrations (MIC) of common pathogens implicated in bone and joint infections in order to determine which antibiotics may have a greater potential in the treatment of such infections. Clinical outcomes were also evaluated as data were available. More than 30 antibiotics were evaluated. Overall, most antibiotics, including amoxicillin, piperacillin/tazobactam, cloxacillin, cephalosporins, carbapenems, aztreonam, aminoglycosides, fluoroquinolones, doxycycline, vancomycin, linezolid, daptomycin, clindamycin, trimethoprim/sulfamethoxazole, fosfomycin, rifampin, dalbavancin, and oritavancin, showed good penetration into bone and joint tissues reaching concentrations exceeding the MIC90 and/or MIC breakpoints of common bone and joint infections pathogens. Few exceptions include penicillin and metronidazole which showed a lower than optimum penetration into bones, and the latter as well as flucloxacillin had poor profiles in terms of joint space penetration. Of note, studies on joint space penetration were fewer than studies on bone tissue penetration. Although clinical studies in osteomyelitis and septic arthritis are not available for all of the evaluated antibiotics, these pharmacokinetic results indicate that agents with good penetration profiles would have a potential utilization in such infections.

FULL TEXT

https://www.ijidonline.com/article/S1201-9712(19)30069-4/fulltext

PDF

https://www.ijidonline.com/article/S1201-9712(19)30069-4/pdf

Group B Streptococcus in surgical site and non-invasive bacterial infections worldwide: A systematic review and meta-analysis

International Journal of Infectious Diseases June 2019 V.83 P.116-129

Simon M. Collin, Nandini Shetty, Rebecca Guy, Victoria N. Nyaga, Ann Bull, Michael J. Richards, Tjallie I.I. van der Kooi, Mayke B.G. Koek, Mary De Almeida, Sally A. Roberts, Theresa Lamagni

Highlights

• This review obtained data on group B Streptococcus infection from 67 countries.
• Group B Streptococcus is implicated in a small proportion of non-invasive infections.
• Group B Streptococcus causes 10% of caesarean section invasive surgical infections.

Objectives

The epidemiology of disease caused by group B Streptococcus (GBS; Streptococcus agalactiae) outside pregnancy and the neonatal period is poorly characterized. The aim of this study was to quantify the role of GBS as a cause of surgical site and non-invasive infections at all ages.

Methods

A systematic review (PROSPERO CRD42017068914) and meta-analysis of GBS as a proportion (%) of bacterial isolates from surgical site infection (SSI), skin/soft tissue infection (SSTI), urinary tract infection (UTI), and respiratory tract infection (RTI) was conducted.

Results

Seventy-four studies and data sources were included, covering 67 countries. In orthopaedic surgery, GBS accounted for 0.37% (95% confidence interval (CI) 0.08–1.68%), 0.87% (95% CI 0.33–2.28%), and 1.46% (95% CI 0.49–4.29%) of superficial, deep, and organ/space SSI, respectively. GBS played a more significant role as a cause of post-caesarean section SSI, detected in 2.92% (95% CI 1.51–5.55%), 1.93% (95% CI 0.97–3.81%), and 9.69% (95% CI 6.72–13.8%) of superficial, deep, and organ/space SSI. Of the SSTI isolates, 1.89% (95% CI 1.16–3.05%) were GBS. The prevalence of GBS in community and hospital UTI isolates was 1.61% (1.13–2.30%) and 0.73% (0.43–1.23%), respectively. GBS was uncommonly associated with RTI, accounting for 0.35% (95% CI 0.19–0.63%) of community and 0.27% (95% CI 0.15–0.48%) of hospital RTI isolates.

Conclusions

GBS is implicated in a small proportion of surgical site and non-invasive infections, but a substantial proportion of invasive SSI post-caesarean section.

FULL TEXT

https://www.ijidonline.com/article/S1201-9712(19)30187-0/fulltext

PDF

https://www.ijidonline.com/article/S1201-9712(19)30187-0/pdf

 

 

Review – Clostridium difficile infection.

European Journal of Clinical Microbiology & Infectious Diseases. June 2019 V.38 N.7

Clostridium difficile (C. difficile) is a Gram-positive, spore-forming, anaerobic bacillus, which is widely distributed in the intestinal tract of humans and animals and in the environment.

In the last decade, the frequency and severity of C. difficile infection has been increasing worldwide to become one of the most common hospital-acquired infections. Transmission of this pathogen occurs by the fecal-oral route and the most important risk factors include antibiotic therapy, old age, and hospital or nursing home stay.

The clinical picture is diverse and ranges from asymptomatic carrier status, through various degrees of diarrhea, to the most severe, life threatening colitis resulting with death. Diagnosis is based on direct detection of C. difficile toxins in feces, most commonly with the use of EIA assay, but no single test is suitable as a stand-alone test confirming CDI.

Antibiotics of choice are vancomycin, fidaxomicin, and metronidazole, though metronidazole is considered as inferior. The goal of this review is to update physicians on current scientific knowledge of C. difficile infection, focusing also on fecal microbiota transplantation which is a promising therapy.

FULL TEXT

https://link.springer.com/article/10.1007/s10096-019-03539-6?wt_mc=alerts.TOCjournals&utm_source=toc&utm_medium=email&utm_campaign=toc_10096_38_7

PDF

https://link.springer.com/content/pdf/10.1007%2Fs10096-019-03539-6.pdf

REVISION – Difusión de los antibióticos en el sistema nervioso central

Revista Española de Quimioterapia Febrero 2018 V.31 N.1 P.1–12.

José María Cabrera-Maqueda,corresponding author1 Luna Fuentes Rumí,1 Gabriel Valero López,1 Ana Esther Baidez Guerrero,1 Estefanía García Molina,1 José Díaz Pérez,1 and Elisa García-Vázquez2

RESUMEN

Las infecciones del SNC causadas por patógenos mutiresistentes suponen un reto terapéutico. El paso de fluidos y de solutos al SNC está estrechamente regulado a través de la BHE.La penetración de cualquier fármaco, inclusive los ATB, en el LCR depende del tamaño molecular, la lipofilicidad, la unión a proteínas plasmáticas y su afinidad por transportadores de la BHE. La relación entre el área bajo la curva en el LCR y el suero AUCCSF (Area Bajo la Curva en LCR)/AUCS (Area Bajo la Curva en suero) de una sustancia es el parámetro más preciso para determinar su capacidad de difusión.

Linezolid, algunas quinolonas y metronidazol consiguen altas concentraciones en LCR y son útiles para tratar microorganismos sensibles. Algunos ATB cuya permeabilidad a través de la BHE es baja pueden ser administrados directamente en el ventrículo a la vez que se realiza infusión IV. El ATB ideal para tratar una infección del SNC es pequeño, no tiene alta tasa de unión a proteínas plasmáticas, es moderadamente lipofílico y no es un ligando de alta afinidad a bombas de expulsión de la BHE.

Conocer la farmacocinética de los ATB y su interacción con la BHE permitirá mejorar el tratamiento de los pacientes con infecciones del SNC. En este artículo se exponen las propiedades físico-químicas de los principales grupos de ATB para evaluar cuáles son más prometedores en el tratamiento de las infecciones del SNC y cómo usarlos en la práctica clínica habitual.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159365/pdf/revespquimioter-31-1.pdf

Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America

Clinical Infectious Diseases May 15, 2019 V.68 N.10 P.1611-1615

IDSA GUIDELINES

Asymptomatic bacteriuria (ASB) is a common finding in many populations, including healthy women and persons with underlying urologic abnormalities. The 2005 guideline from the Infectious Diseases Society of America recommended that ASB should be screened for and treated only in pregnant women or in an individual prior to undergoing invasive urologic procedures. Treatment was not recommended for healthy women; older women or men; or persons with diabetes, indwelling catheters, or spinal cord injury. The guideline did not address children and some adult populations, including patients with neutropenia, solid organ transplants, and nonurologic surgery. In the years since the publication of the guideline, further information relevant to ASB has become available. In addition, antimicrobial treatment of ASB has been recognized as an important contributor to inappropriate antimicrobial use, which promotes emergence of antimicrobial resistance. The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB.

FULL TEXT

https://academic.oup.com/cid/article/68/10/1611/5481760

PDF (CLIC en PDF)

A review of the value of quadrivalent influenza vaccines and their potential contribution to influenza control.

Hum Vaccin Immunother. July 3, 2017 V.13 N.7 P.1640-1652.

Ray R1, Dos Santos G2, Buck PO3, Claeys C1, Matias G1, Innis BL3, Bekkat-Berkani R1.

Author information

1 a GSK , Wavre , Belgium.

2 b Business & Decision Life Sciences , Brussels , Belgium (on behalf of GSK).

3 c GSK , Philadelphia , PA , USA.

Abstract

The contribution of influenza B to the seasonal influenza burden varies from year-to-year. Although 2 antigenically distinct influenza B virus lineages have co-circulated since 2001, trivalent influenza vaccines (TIVs) contain antigens from only one influenza B virus. B-mismatch or co-circulation of both B lineages results in increased morbidity and mortality attributable to the B lineage absent from the vaccine. Quadrivalent vaccines (QIVs) contain both influenza B lineages. We reviewed currently licensed QIVs and their value by focusing on the preventable disease burden. Modeling studies support that QIVs are expected to prevent more influenza cases, hospitalisations and deaths than TIVs, although estimates of the case numbers prevented vary according to local specificities. The value of QIVs is demonstrated by their capacity to broaden the immune response and reduce the likelihood of a B-mismatched season. Some health authorities have preferentially recommended QIVs over TIVs in their influenza prevention programmes.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512791/pdf/khvi-13-07-1313375.pdf