Current Perspectives on Treatment of Gram-Positive Infections in India: What Is the Way Forward?

The emerging antimicrobial resistance leading to gram-positive infections (GPIs) is one of the major public health threats worldwide. GPIs caused by multidrug resistant bacteria can result in increased morbidity and mortality rates along with escalated treatment cost and hospitalisation stay. In India, GPIs, particularly methicillin-resistant Staphylococcus aureus (MRSA) prevalence among invasive S. aureus isolates, have been reported to increase exponentially from 29% in 2009 to 47% in 2014. Apart from MRSA, rising prevalence of vancomycin-resistant enterococci (VRE), which ranges from 1 to 9% in India, has raised concerns. Moreover, the overall mortality rate among patients with multidrug resistant GPIs in India is reported to be 10.8% and in ICU settings, the mortality rate is as high as 16%. Another challenge is the spectrum of adverse effects related to the safety and tolerability profile of the currently available drugs used against GPIs which further makes the management and treatment of these multidrug resistant organisms a complex task. Judicious prescription of antimicrobial agents, implementation of antibiotic stewardship programmes, and antibiotic policies in hospitals are essential to reduce the problem of drug-resistant infections in India. The most important step is development of newer antimicrobial agents with novel mechanisms of action and favourable pharmacokinetic profile. This review provides a synopsis about the current burden, treatment options, and the challenges faced by the clinicians in the management of GPIs such as MRSA, Quinolone-resistant Staphylococcus, VRE, and drug-resistant pneumococcus in India.

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Resistance to nitrofurantoin is an indicator of extensive drug-resistant (XDR) Enterobacteriaceae

Journal of Medical Microbiology ◽

10.1099/jmm.0.001347 ◽

2021 ◽

Vol 70 (4) ◽

Author(s):

Balaram Khamari ◽

Prakash Kumar ◽

Bulagonda Eswarappa Pradeep

Keyword(s):

Antimicrobial Agents ◽

Efflux Pump ◽

Treatment Options ◽

Strong Association ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Resistant Bacteria ◽

Drug Resistant ◽

Content Type ◽

Link Type

Introduction. Nitrofurantoin is one of the preferred antibiotics in the treatment of uropathogenic multidrug-resistant (MDR) infections. However, resistance to nitrofurantoin in extensively drug-resistant (XDR) bacteria has severely limited the treatment options. Gap statement. Information related to co-resistance or collateral sensitivity (CS) with reference to nitrofurantoin resistant bacteria is limited. Aim. To study the potential of nitrofurantoin resistance as an indicator of the XDR phenotype in Enterobacteriaceae . Methods. One hundred (45 nitrofurantoin-resistant, 21 intermediately resistant and 34 nitrofurantoin-susceptible) Enterobacteriaceae were analysed in this study. Antibiotic susceptibility testing (AST) against nitrofurantoin and 17 other antimicrobial agents across eight different classes was performed by using the Vitek 2.0 system. The isolates were screened for the prevalence of acquired antimicrobial resistance (AMR) and efflux pump genes by PCR. Results. In total, 51 % of nitrofurantoin-resistant and 28 % of intermediately nitrofurantoin resistant isolates exhibited XDR characteristics, while only 3 % of nitrofurantoin-sensitive isolates were XDR (P=0.0001). Significant co-resistance was observed between nitrofurantoin and other tested antibiotics (β-lactam, cephalosporin, carbapenem, aminoglycoside and tetracycline). Further, the prevalence of AMR and efflux pump genes was higher in the nitrofurantoin-resistant strains compared to the susceptible isolates. A strong association was observed between nitrofurantoin resistance and the presence of bla PER-1, bla NDM-1, bla OXA-48, ant(2) and oqxA-oqxB genes. Tigecycline (84 %) and colistin (95 %) were the only antibiotics to which the majority of the isolates were susceptible. Conclusion. Nitrofurantoin resistance could be an indicator of the XDR phenotype among Enterobacteriaceae , harbouring multiple AMR and efflux pump genes. Tigecycline and colistin are the only antibiotics that could be used in the treatment of such XDR infections. A deeper understanding of the co-resistance mechanisms in XDR pathogens and prescription of AST-based appropriate combination therapy may help mitigate this problem.

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Emerging Treatment Options for Infections by Multidrug-Resistant Gram-Positive Microorganisms

Microorganisms ◽

10.3390/microorganisms8020191 ◽

2020 ◽

Vol 8 (2) ◽

pp. 191 ◽

Cited By ~ 4

Author(s):

Despoina Koulenti ◽

Elena Xu ◽

Andrew Song ◽

Isaac Yin Sum Mok ◽

Drosos E. Karageorgopoulos ◽

...

Keyword(s):

Safety Profile ◽

Bacterial Infections ◽

Antimicrobial Agents ◽

Treatment Options ◽

Multidrug Resistant ◽

Current Treatment ◽

Multi Drug Resistance ◽

Gram Positive ◽

Treatment Regimens ◽

Gram Positive Bacteria

Antimicrobial agents are currently the mainstay of treatment for bacterial infections worldwide. However, due to the increased use of antimicrobials in both human and animal medicine, pathogens have now evolved to possess high levels of multi-drug resistance, leading to the persistence and spread of difficult-to-treat infections. Several current antibacterial agents active against Gram-positive bacteria will be rendered useless in the face of increasing resistance rates. There are several emerging antibiotics under development, some of which have been shown to be more effective with an improved safety profile than current treatment regimens against Gram-positive bacteria. We will extensively discuss these antibiotics under clinical development (phase I-III clinical trials) to combat Gram-positive bacteria, such as Staphylococcus aureus, Enterococcus faecium and Streptococcus pneumoniae. We will delve into the mechanism of actions, microbiological spectrum, and, where available, the pharmacokinetics, safety profile, and efficacy of these drugs, aiming to provide a comprehensive review to the involved stakeholders.

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Biodegradable Nanofibrous Membranes for Medical and Personal Protection Applications: Manufacturing, Anti-COVID-19 and Anti-Multidrug Resistant Bacteria Evaluation

Materials ◽

10.3390/ma14143862 ◽

2021 ◽

Vol 14 (14) ◽

pp. 3862

Author(s):

Latifah Abdullah Alshabanah ◽

Mohamed Hagar ◽

Laila A. Al-Mutabagani ◽

Ghada M. Abozaid ◽

Salwa M. Abdallah ◽

...

Keyword(s):

Antimicrobial Agents ◽

Multidrug Resistant ◽

Standard Test ◽

Test Method ◽

Resistant Bacteria ◽

Drug Resistant ◽

Personal Protection ◽

Multidrug Resistant Bacteria ◽

Standard Test Method ◽

Nanofibrous Membranes

Biodegradable nanofibrous hybrid membranes of polyvinyl alcohol (PVA) with ZnO and CuO nanoparticles were manufactured and characterized, and their anti-COVID-19 and anti-multidrug resistant bacteria activities were also evaluated. The morphological structures of the prepared PVA composites nanofibers were observed by scanning electron microscope (SEM), which revealed a homogenous pattern of the developed nanofibers, with an average fibrous diameter of 200–250 nm. Moreover, the results of the SEM showed that the fiber size changed with the type and the concentration of the metal oxide. Moreover, the antiviral and antibacterial potential capabilities of the developed nanofibrous membranes were tested in blocking the viral fusion of SARS-COV-2, as a representative activity for COVID-19 deactivation, as well as for their activity against a variety of bacterial strains, including multi-drug resistant bacteria (MDR). The results revealed that ZnO loaded nanofibers were more potent antiviral agents than their CuO analogues. This antiviral action was attributed to the fact that inorganic metallic compounds have the ability to extract hydrogen bonds with viral proteins, causing viral rupture or morphological changes. On the other hand, the anti-multi-drug resistant activity of the prepared nanofibers was also evaluated using two techniques; the standard test method for determining the antimicrobial activity of immobilized antimicrobial agents under dynamic contact conditions and the standard test method for determining the activity of incorporated antimicrobial agents in polymeric or hydrophobic materials. Both techniques proved the superiority of the ZnO loaded nanofibers over the CuO loaded fibers. The results of the antiviral and antibacterial tests showed the effectiveness of such nanofibrous formulas, not only for medical applications, but also for the production of personal protection equipment, such as gowns and textiles.

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Efficacy of Tigecycline and Linezolid Against Pan-Drug-Resistant Bacteria Isolated From Companion Dogs in South Korea

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.693506 ◽

2021 ◽

Vol 8 ◽

Author(s):

Dong-Hyun Kim ◽

Jung-Hyun Kim

Keyword(s):

South Korea ◽

Antimicrobial Agents ◽

Companion Animals ◽

Multidrug Resistant ◽

Diffusion Method ◽

Clinical Samples ◽

Resistant Bacteria ◽

Drug Resistant ◽

Multidrug Resistant Bacteria ◽

Companion Dogs

The emergence of multidrug-resistant bacteria in companion animals is an increasing concern in view of the concept of One Health. The antimicrobials linezolid (LZD) and tigecycline (TGC) are effective against multidrug-resistant bacteria isolated from humans; however, thus far, no previous study has evaluated the efficacy of these drugs against bacteria isolated from companion animals. This study aimed to evaluate the efficacy of LZD and TGC against bacteria that were isolated from companion dogs and showed resistance to all classes of antimicrobial agents. Clinical samples (auditory channel, eye, skin, and urine) were collected from dogs that visited the Veterinary Medical Teaching Hospital of Konkuk University (Seoul, South Korea) from October 2017 to September 2020. In total, 392 bacterial isolates were obtained, of which 85 were resistant to all classes of antimicrobial agents tested and were, therefore, considered potentially pan-drug resistant (PDR). The susceptibility of isolates to LZD and TGC was determined by the disk diffusion method and interpreted using the Clinical Laboratory Standards Institute guidelines. In total, 95.6% (43/45) and 97.8% (44/45) of gram-positive isolates were susceptible to LZD and TGC, respectively, whereas 82.5% (33/40) of gram-negative isolates were sensitive to TGC. In conclusion, both agents showed favorable efficacy, with the susceptibility rates for all potential PDR bacteria, except Pseudomonas spp., ranging from 72.7 to 100%. Thus, these drugs may serve as excellent antimicrobial options for veterinary medicine in the future.

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Current Mechanism of Bacterial Resistance to Antimicrobials

SAMRIDDHI A Journal of Physical Sciences Engineering and Technology ◽

10.18090/samriddhi.v10i01.8 ◽

2018 ◽

Vol 10 (01) ◽

pp. 55-64

Author(s):

Sonali Gangwar ◽

Keerti Kaushik ◽

Maya Datt Joshi

Keyword(s):

Molecular Mechanisms ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

Multidrug Resistant ◽

Hospital Environment ◽

Health Concern ◽

Resistant Bacteria ◽

Drug Resistant ◽

Pathogenic Variants ◽

Drug Resistant Bacteria

Serious infectious diseases are caused by bacterial pathogens that represents a serious public health concern. Antimicrobial agents are indicated for the treatment bacterial infections.Various bacteria carries several resistance genes also called multidrug resistant (MDR). Multidrug resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting the reservoirs of antibiotic resistant bacteria are present outside the hospital. Drug resistant bacteria that are selected with a single drug are also frequently multi-drug resistant against multiple structurally different drugs, thus confounding the chemotherapeutic efficacy of infectious disease caused by such pathogenic variants. The molecular mechanisms by which bacteria have common resistance to antibiotics are diverse and complex. This review highlights the mechanism of bacterial resistance to antimicrobials.

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Bacteriocins: An Overview of Antimicrobial, Toxicity, and Biosafety Assessment by in vivo Models

Frontiers in Microbiology ◽

10.3389/fmicb.2021.630695 ◽

2021 ◽

Vol 12 ◽

Author(s):

Diego Francisco Benítez-Chao ◽

Angel León-Buitimea ◽

Jordy Alexis Lerma-Escalera ◽

José Rubén Morones-Ramírez

Keyword(s):

Antimicrobial Agents ◽

Multidrug Resistant ◽

Therapeutic Agents ◽

Resistant Bacteria ◽

Drug Resistant ◽

Infectious Agents ◽

Key Factors ◽

In Vivo Models ◽

Drug Resistant Bacteria

The world is facing a significant increase in infections caused by drug-resistant infectious agents. In response, various strategies have been recently explored to treat them, including the development of bacteriocins. Bacteriocins are a group of antimicrobial peptides produced by bacteria, capable of controlling clinically relevant susceptible and drug-resistant bacteria. Bacteriocins have been studied to be able to modify and improve their physicochemical properties, pharmacological effects, and biosafety. This manuscript focuses on the research being developed on the biosafety of bacteriocins, which is a topic that has not been addressed extensively in previous reviews. This work discusses the studies that have tested the effect of bacteriocins against pathogens and assess their toxicity using in vivo models, including murine and other alternative animal models. Thus, this work concludes the urgency to increase and advance the in vivo models that both assess the efficacy of bacteriocins as antimicrobial agents and evaluate possible toxicity and side effects, which are key factors to determine their success as potential therapeutic agents in the fight against infections caused by multidrug-resistant microorganisms.

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Emerging Treatment Options for Multi-Drug-Resistant Bacterial Infections

Life ◽

10.3390/life11060519 ◽

2021 ◽

Vol 11 (6) ◽

pp. 519

Author(s):

Roberto Giurazza ◽

Maria Civita Mazza ◽

Roberto Andini ◽

Pasquale Sansone ◽

Maria Caterina Pace ◽

...

Keyword(s):

Bacterial Infections ◽

Treatment Options ◽

Resistance Mechanisms ◽

Antimicrobial Treatment ◽

Resistant Bacteria ◽

Drug Resistant ◽

Gram Positive ◽

Strict Adherence ◽

Gram Negative ◽

Gram Positive Cocci

Antimicrobial resistance (AMR) remains one of the top public health issues of global concern. Among the most important strategies for AMR control there is the correct and appropriate use of antibiotics, including those available for the treatment of AMR pathogens. In this article, after briefly reviewing the most important and clinically relevant multi-drug-resistant bacteria and their main resistance mechanisms, we describe the emerging antimicrobial options for both MDR Gram-positive cocci and Gram-negative bacilli, including recently marketed agents, molecules just approved or under evaluation and rediscovered older antibiotics that have regained importance due to their antimicrobial spectrum. Specifically, emerging options for Gram-positive cocci we reviewed include ceftaroline, ceftobiprole, tedizolid, dalbavancin, and fosfomycin. Emerging treatment options for Gram-negative bacilli we considered comprise ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, aztreonam-avibactam, minocycline, fosfomycin, eravacycline, plazomicin, and cefiderocol. An exciting scenario is opening today with the long awaited growing availability of novel molecules for the treatment of AMR bacteria. Knowledge of mechanisms of action and resistance patterns allows physicians to increasingly drive antimicrobial treatment towards a precision medicine approach. Strict adherence to antimicrobial stewardship practices will allow us to preserve the emerging antimicrobials for our future.

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Linezolid treatment of shunt-related cerebrospinal fluid infections in children

Journal of Neurosurgery Pediatrics ◽

10.3171/2009.12.peds09421 ◽

2010 ◽

Vol 5 (5) ◽

pp. 443-448 ◽

Cited By ~ 20

Author(s):

Adem Yılmaz ◽

Nazan Dalgic ◽

Murat Müslüman ◽

Mesut Sancar ◽

Ibrahim Çolak ◽

...

Keyword(s):

Antimicrobial Agents ◽

Shunt Infection ◽

Multidrug Resistant ◽

Drug Resistant ◽

Gram Positive ◽

Vp Shunt ◽

Resistant Strains ◽

The Mean ◽

Shunt Removal ◽

Drug Resistant Strains

Object The emergence of multidrug-resistant bacteria as a cause of ventriculoperitoneal (VP) shunt infection is a disconcerting phenomenon that often requires the use of alternative antimicrobial agents due to resistance against commonly used medications. Linezolid, a member of a new class of antimicrobial agents, has good activity against virtually all important gram-positive pathogens, including multidrug-resistant gram-positive pathogens. The object of this article is to report a single-center experience with linezolid treatment in 6 young patients with VP shunt infections caused by drug-resistant strains. Methods The authors reviewed the records of 6 pediatric patients who developed VP shunt infection and in whom initial antimicrobial treatment regimens, including vancomycin, either failed or were associated with vancomycin-resistant enterococcus. All 6 patients were treated at their hospital between July 1, 2008, and June 29, 2009. The patients' demographic and clinical characteristics, underlying diseases, clinical manifestations, laboratory results, and various treatment modalities used before linezolid therapy were evaluated. Results The 6 patients included were 2 boys and 4 girls with a mean (± SD) age of 11.83 ± 12 months (range 4–36 months). Five patients had acquired an infection within 4 months (mean 7.50 ± 13.51 months, range 1–35 months) after shunt insertion. Four patients were treated with external ventricular drainage. Two patients' parents refused to allow shunt removal and placement of an external ventricular drain. The CSF was clear of bacterial growth within a mean of 3.67 ± 1.36 days (range 2–6 days) after initiation of linezolid treatment. The mean duration of linezolid treatment was 18.17 ± 3.31 days (range 14–21 days). Microbiological clearance of CSF and clinical cure were achieved in all patients. No laboratory or clinical side effects were observed during the treatment period. The mean length of hospital stay was 22.8 ± 4.96 days (range 17–28 days). Conclusions Linezolid could be an appropriate treatment alternative in children with ventriculostomy-related CSF infections caused by drug-resistant strains, including cases in which shunt removal is not an option. Well-designed prospective studies providing additional information on linezolid levels in plasma and CSF are necessary to confirm the authors' observations.

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