The conundrum of bacteria-specific antibiotics.

There is a continual debate on the pros and cons of broad-spectrum versus pathogen-specific antibiotics. The unmet need for a solution for antimicrobial resistance (AMR) has put this argument into sharper focus. A shortage of clinically differentiated antibiotics in late-stage clinical development coupled with the global unmet need in the face of the AMR onslaught has exacerbated the treatment options of drug-resistant bacterial infections. An added dimension to this problem is the current understanding of dysbiosis caused by antibiotics, often leading to negative fallout in immunocompromised patients. We attempt to deconstruct the nuances of this debate from an antibiotics discovery and a clinical standpoint.

[1]  C. Alvarez,et al.  Controversies in the Prevention and Treatment of Clostridioides difficile Infection in Adults: A Narrative Review , 2023, Microorganisms.

[2]  Zhiguo Yuan,et al.  Antidepressants can induce mutation and enhance persistence toward multiple antibiotics , 2023, Proceedings of the National Academy of Sciences of the United States of America.

[3]  K. Garey,et al.  Emerging Options for the Prevention and Management of Clostridioides difficile Infection , 2023, Drugs.

[4]  M. Manzi,et al.  Incidence of Surgical Site Infection and Use of Antibiotics among Patients Who Underwent Caesarean Section and Herniorrhaphy at a Regional Referral Hospital, Sierra Leone , 2022, International journal of environmental research and public health.

[5]  A. Kusiak,et al.  Probiotics: Should All Patients Take Them? , 2021, Microorganisms.

[6]  N. Bharatham,et al.  Azaindole Based Potentiator of Antibiotics against Gram-Negative Bacteria. , 2021, ACS infectious diseases.

[7]  E. Montassier,et al.  Impact of non-antibiotic drugs on the human intestinal microbiome , 2021, Expert review of molecular diagnostics.

[8]  R. Ahmad,et al.  Association of the microbiome with colorectal cancer development (Review). , 2021, International journal of oncology.

[9]  P. Hergenrother,et al.  Facilitating Compound Entry as a Means to Discover Antibiotics for Gram-Negative Bacteria. , 2021, Accounts of chemical research.

[10]  M. Ashworth,et al.  Association between antibiotics and gut microbiome dysbiosis in children: systematic review and meta-analysis , 2021, Gut microbes.

[11]  S. Solomon,et al.  Could Perturbation of Gut Microbiota Possibly Exacerbate the Severity of COVID-19 via Cytokine Storm? , 2021, Frontiers in Immunology.

[12]  P. Sestili,et al.  Gut Microbiota Status in COVID-19: An Unrecognized Player? , 2020, Frontiers in Cellular and Infection Microbiology.

[13]  F. Guarner,et al.  Antibiotics as Major Disruptors of Gut Microbiota , 2020, Frontiers in Cellular and Infection Microbiology.

[14]  B. Lv,et al.  The prophylactic effects of BIFICO on the antibiotic-induced gut dysbiosis and gut microbiota , 2020, Gut Pathogens.

[15]  A. Huntley,et al.  Antibiotic-induced changes in the human gut microbiota for the most commonly prescribed antibiotics in primary care in the UK: a systematic review , 2020, BMJ Open.

[16]  M. Khurshid,et al.  CRISPR-Cas system: a potential alternative tool to cope antibiotic resistance , 2020, Antimicrobial Resistance & Infection Control.

[17]  M. Mckenna The antibiotic paradox: why companies can’t afford to create life-saving drugs , 2020, Nature.

[18]  Jessica Pourraz,et al.  Phage therapy as a potential solution in the fight against AMR: obstacles and possible futures , 2020, Palgrave Communications.

[19]  D. Andersson,et al.  Molecular mechanisms of collateral sensitivity to the antibiotic nitrofurantoin , 2020, PLoS biology.

[20]  A. Torres,et al.  An overview of guidelines for the management of hospital-acquired and ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria. , 2019, Current opinion in infectious diseases.

[21]  Aaron W. Miller,et al.  Defining Dysbiosis for a Cluster of Chronic Diseases , 2019, Scientific Reports.

[22]  K. Pollard,et al.  New insights from uncultivated genomes of the global human gut microbiome , 2019, Nature.

[23]  M. Gajdács The Concept of an Ideal Antibiotic: Implications for Drug Design , 2019, Molecules.

[24]  R. Pathania,et al.  Efflux pump inhibitors for bacterial pathogens: From bench to bedside , 2019, The Indian journal of medical research.

[25]  B. Luisi,et al.  Multidrug efflux pumps: structure, function and regulation , 2018, Nature Reviews Microbiology.

[26]  L. Alcaraz,et al.  Variability of Bacterial Essential Genes Among Closely Related Bacteria: The Case of Escherichia coli , 2018, Front. Microbiol..

[27]  Anirudh P. Shanbhag,et al.  Nitrothiophene carboxamides, a novel narrow spectrum antibacterial series: Mechanism of action and Efficacy , 2018, Scientific Reports.

[28]  D. Zurawski,et al.  Narrow-Spectrum Antibacterial Agents. , 2018, MedChemComm.

[29]  Vanni Bucci,et al.  Antibiotic treatment for Tuberculosis induces a profound dysbiosis of the microbiome that persists long after therapy is completed , 2017, Scientific Reports.

[30]  L. Silver Appropriate Targets for Antibacterial Drugs. , 2016, Cold Spring Harbor perspectives in medicine.

[31]  B. Geller,et al.  Antisense antimicrobial therapeutics , 2016, Current Opinion in Microbiology.

[32]  G. Meletis,et al.  Carbapenem resistance: overview of the problem and future perspectives , 2016, Therapeutic advances in infectious disease.

[33]  Z. Tandoğdu,et al.  Global epidemiology of urinary tract infections , 2016, Current opinion in infectious diseases.

[34]  A. Pantosti,et al.  Antimicrobial resistance: a global multifaceted phenomenon , 2015, Pathogens and global health.

[35]  D. Snydman,et al.  Risk and safety of probiotics. , 2015, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[36]  K. Mullis,et al.  Retargeting pre-existing human antibodies to a bacterial pathogen with an alpha-Gal conjugated aptamer , 2015, Journal of Molecular Medicine.

[37]  Onkar C. Swami,et al.  Strategies to combat antimicrobial resistance. , 2014, Journal of clinical and diagnostic research : JCDR.

[38]  Sang Hee Lee,et al.  Strategies to Minimize Antibiotic Resistance , 2013, International journal of environmental research and public health.

[39]  A. Delcour,et al.  Outer membrane permeability and antibiotic resistance. , 2009, Biochimica et biophysica acta.

[40]  J. Pagés,et al.  Intracellular accumulation of linezolid in Escherichia coli, Citrobacter freundii and Enterobacter aerogenes: role of enhanced efflux pump activity and inactivation. , 2007, The Journal of antimicrobial chemotherapy.

[41]  C. Hutchison,et al.  Essential genes of a minimal bacterium. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[42]  A. L. Koch Were Gram-positive rods the first bacteria? , 2003, Trends in microbiology.

[43]  W. Hammes,et al.  Safety of probiotics that contain lactobacilli or bifidobacteria. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[44]  E. Koonin,et al.  Essential genes are more evolutionarily conserved than are nonessential genes in bacteria. , 2002, Genome research.

[45]  J. Sobel,et al.  Antibiotics for gram-positive bacterial infections. Vancomycin, teicoplanin, quinupristin/dalfopristin, and linezolid. , 2000, Infectious disease clinics of North America.

[46]  M. Vaara Agents that increase the permeability of the outer membrane , 1992 .