Novel Antibiotics for Multidrug-Resistant Gram-Positive Microorganisms

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Abstract

Increasing multidrug-resistance to Gram-positive pathogens, particularly to staphylococci, enterococci and streptococci, is a major problem, resulting in significant morbidity, mortality and healthcare costs. In recent years, only a small number of novel antibiotics effective against Gram-positive bacteria has been approved. This review will discuss the current evidence for novel branded antibiotics that are highly effective in the treatment of multidrug-resistant infections by Gram-positive pathogens, namely ceftobiprole, ceftaroline, telavancin, oritavancin, dalbavancin, tedizolid, besifloxacin, delafloxacin, ozenoxacin, and omadacycline. The mechanism of action, pharmacokinetics, microbiological spectrum, efficacy and safety profile will be concisely presented. As for any emerging antibiotic agent, resistance is likely to develop against these highly effective antibiotics. Only through appropriate dosing, utilization and careful resistance development monitoring will these novel antibiotics continue to treat Gram-positive pathogens in the future.

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Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic.

Michael David, Robert S Daum (2010)

Staphylococcus aureus is an important cause of skin and soft-tissue infections (SSTIs), endovascular infections, pneumonia, septic arthritis, endocarditis, osteomyelitis, foreign-body infections, and sepsis. Methicillin-resistant S. aureus (MRSA) isolates were once confined largely to hospitals, other health care environments, and patients frequenting these facilities. Since the mid-1990s, however, there has been an explosion in the number of MRSA infections reported in populations lacking risk factors for exposure to the health care system. This increase in the incidence of MRSA infection has been associated with the recognition of new MRSA clones known as community-associated MRSA (CA-MRSA). CA-MRSA strains differ from the older, health care-associated MRSA strains; they infect a different group of patients, they cause different clinical syndromes, they differ in antimicrobial susceptibility patterns, they spread rapidly among healthy people in the community, and they frequently cause infections in health care environments as well. This review details what is known about the epidemiology of CA-MRSA strains and the clinical spectrum of infectious syndromes associated with them that ranges from a commensal state to severe, overwhelming infection. It also addresses the therapy of these infections and strategies for their prevention.

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Bacteria antibiotic resistance: New challenges and opportunities for implant-associated orthopedic infections

Bingyun Li, Thomas Webster (2017)

There has been a dramatic increase in the emergence of antibiotic resistant bacterial strains, which has made antibiotic choices for infection control increasingly limited and more expensive. In the U.S. alone, antibiotic resistant bacteria cause at least 2 million infections and 23,000 deaths a year resulting in a $55–70 billion per year economic impact. Antibiotics are critical to the success of surgical procedures including orthopaedic prosthetic surgeries, and antibiotic resistance is occurring in nearly all bacteria that infect people, including the most common bacteria that cause orthopaedic infections, such as Staphylococcus aureus ( S. aureus ). Most clinical cases of orthopaedic surgeries have shown that patients infected with antibiotic resistant bacteria, such as methicillin resistant S. aureus (MRSA), are associated with increased morbidity and mortality. This paper reviews the severity of antibiotic resistance at the global scale, the consequences of antibiotic resistance, and the pathways bacteria used to develop antibiotic resistance. It highlights the opportunities and challenges in limiting antibiotic resistance through approaches like the development of novel, non-drug approaches to reduce bacteria functions related to orthopaedic implant-associated infections.

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Adverse clinical and economic outcomes attributable to methicillin resistance among patients with Staphylococcus aureus surgical site infection.

John J. Engemann, Steven P. Briggs, Keith S. Kaye … (2003)

Data for 479 patients were analyzed to assess the impact of methicillin resistance on the outcomes of patients with Staphylococcus aureus surgical site infections (SSIs). Patients infected with methicillin-resistant S. aureus (MRSA) had a greater 90-day mortality rate than did patients infected with methicillin-susceptible S. aureus (MSSA; adjusted odds ratio, 3.4; 95% confidence interval, 1.5-7.2). Patients infected with MRSA had a greater duration of hospitalization after infection (median additional days, 5; P<.001), although this was not significant on multivariate analysis (P=.11). Median hospital charges were 29,455 dollars for control subjects, 52,791 dollars for patients with MSSA SSI, and 92,363 dollars for patients with MRSA SSI (P<.001 for all group comparisons). Patients with MRSA SSI had a 1.19-fold increase in hospital charges (P=.03) and had mean attributable excess charges of 13,901 dollars per SSI compared with patients who had MSSA SSIs. Methicillin resistance is independently associated with increased mortality and hospital charges among patients with S. aureus SSI.

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Journal

Journal ID (nlm-ta): Microorganisms

Journal ID (iso-abbrev): Microorganisms

Journal ID (publisher-id): microorganisms

Title: Microorganisms

Publisher: MDPI

ISSN (Electronic): 2076-2607

Publication date (Electronic): 18 August 2019

Publication date Collection: August 2019

Volume: 7

Issue: 8

Electronic Location Identifier: 270

Affiliations

[1 ]UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia

[2 ]2nd Critical Care Department, Attikon University Hospital, 12462 Athens, Greece

[3 ]4th Department of Internal Medicine, Attikon University Hospital, 12462 Athens, Greece

[4 ]Department of Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Brisbane 4029, Australia

[5 ]Anesthesiology and Critical Care, Centre Hospitalier Universitaire De Nîmes (CHU), University of Montpellier, 30029 Nîmes, France

Author notes

[* ]Correspondence: d.koulenti@ 123456uq.edu.au

[†]

Equal contribution-both 3rd authors.

[‡]

They are joint senior authors.

Author information

Despoina Koulenti https://orcid.org/0000-0003-4364-2612

Drosos E. Karageorgopoulos https://orcid.org/0000-0002-9959-9978

Sotirios Tsiodras https://orcid.org/0000-0002-0463-4321

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Publisher ID: microorganisms-07-00270

DOI: 10.3390/microorganisms7080270

PMC ID: 6723731

PubMed ID: 31426596

SO-VID: 781ea72e-895e-4c14-b00e-4b165f348aee

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Novel Antibiotics for Multidrug-Resistant Gram-Positive Microorganisms

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Abstract

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Coronaviruses, COVID-19 and SARS-CoV-2

Most cited references 135

Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic.

Bacteria antibiotic resistance: New challenges and opportunities for implant-associated orthopedic infections

Adverse clinical and economic outcomes attributable to methicillin resistance among patients with Staphylococcus aureus surgical site infection.

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