AG are neutralized by specific enzymes: Phosphoryl-transferases, nucleotidyl-transferases or adenylyl-transferases, and AACs. These aminoglycoside-modifying enzymes AMEs reduce affinity of a modified molecule, impede binding to the 30S ribosomal subunit,[ 28 ] and provide extended spectrum resistance to AG's and FQ.
Few Gram-positive and Gram-negative bacteria and some of Haemophilus influenzae strains are resistant to chloramphenicol, and they have an enzyme chloramphenicol transacetylase that acetylates hydroxyl groups of chloramphenicol. Modified chloramphenicol is unable to bind to a ribosomal 50S subunit properly. Resistance mechanism of various antibiotics is described in Table 1. The discovery of antibiotics led to sigh of relief, that now no bacteria will reside in this planet.
With time, the bacteria have become smarter, and along with it, massive usage of antibiotics in clinical practice has resulted in resistance of bacteria to antimicrobial agents. Better understanding of the mechanisms of antibiotic resistance, will help clinicians regarding usage of antibiotics in different situations. National Center for Biotechnology Information , U. J Anaesthesiol Clin Pharmacol.
Author information Copyright and License information Disclaimer. Address for correspondence: Dr. E-mail: moc. This article has been cited by other articles in PMC. Abstract Infections account for a major cause of death throughout the developing world. Keywords: Antibiotics, antimicrobial resistance, bacterial cell wall, mechanism of action. Introduction The struggle of mankind against infectious diseases is well known.
Basic Anatomy of Bacterial Cell The Gram-positive bacteria consists of cytoplasmic membrane surrounded by a tough and rigid mesh called cell wall. Open in a separate window.
Figure 1. Classification of Antibiotics on the Basis of Mechanism of Action The antibiotics are classified on the basis of mechanism of action as described in Figure 2. Figure 2. Antibiotics targeting cell wall Bacterial cells are surrounded by a cell wall made of peptidoglycan, which consists of long sugar polymers. Figure 3. Glycopeptides The glycopeptides binds to D-alanyl D-alanine portion of peptide side chain of the precursor peptidoglycan subunit.
Figure 4. Inhibitors of 30S subunit Aminoglycosides The aminoglycosides AG's are positively-charged molecules which attach to the OM which is negatively charged leading to formation of large pores, and thus allow antibiotic penetration inside the bacterium.
Tetracyclines Tetracyclines, such as tetracycline, chlortetracycline, doxycycline, or minocycline, act upon the conserved sequences of the 16S r-RNA of the 30S ribosomal subunit to prevent binding of t-RNA to the A site.
Inhibitors of 50S subunit Chloramphenicol It interacts with the conserved sequences of the peptidyl transferase cavity of the 23S r-RNA of the 50S subunit. Oxazolidinones Linezolid is a recently approved member of novel class of antibiotic of this group which is completely synthetic. Folic acid metabolism inhibitors Sulfonamides and trimethoprim Each of these drugs inhibits distinct steps in folic acid metabolism.
Mechanisms of Antimicrobial Resistance Prevention of accumulation of antimicrobials either by decreasing uptake or increasing efflux of the antimicrobial from the cell i. Efflux pumps Membrane proteins that export antibiotics from the cell and maintain their low-intracellular concentrations are called efflux pumps. Modification of target molecule Natural variations or acquired changes in the target sites of antimicrobials that prevent drug binding is a common mechanism of resistance.
Chloramphenicol-acetyl-transferases Few Gram-positive and Gram-negative bacteria and some of Haemophilus influenzae strains are resistant to chloramphenicol, and they have an enzyme chloramphenicol transacetylase that acetylates hydroxyl groups of chloramphenicol. Table 1 Resistance mechanism of individual antibiotics. Conclusion The discovery of antibiotics led to sigh of relief, that now no bacteria will reside in this planet. Financial support and sponsorship Nil.
Conflicts of interest There are no conflicts of interest. References 1. Hauser AR, editor. Cell envelope. Antibiotic Basic for Clinicians. Ltd; Glycopeptide and lipoglycopeptide antibiotics. Also: Enterococcus, Candida. Consider adding Vancomycin especially if history of prior infection, chronic urinary catheters or stents. Streptococcus species most commonly Group A , S.
More unusual pathogens are possible depending on risk factors i. Oral options: Cephalexin mg po q6 hours, Clindamycin, Dicloxacillin. Add MRSA coverage if purulent or severe disease. Oral options include Bactrim 2 DS tabs bid best or Doxycycline mg po bid both have poor strep coverage so should be paired with one of the oral beta-lactams.
Streptococcus species, S. Type I is polymicrobial Streptococci, Gram negatives and also involves anaerobes. In addition to emergent surgical debridement: 1. Depends on clinical course should continue at least until no more surgical debridement necessary and minimum of days. In addition to surgical drainage, empiric antibiotics based on gram stain: 1. Gram positive cocci in clusters likely S. Gram negative cocci likely Neisseria : Ceftriaxone 1 g IV qday 3.
Duration depends on pathogen range days. Steroids should be stopped after 4 days, or if proven to be due to another organism. Depends on pathogen range days if otherwise uncomplicated course. Oral and enteric streptococci, gram negative rods including Pseudomonas, Candida. Cefepime 2 g IV q8 hours 2. Main side effects: Hypersensitivity reactions including anaphylaxis, Rashes, Bone marrow suppression, Interstitial Nephritis, GI nausea, diarrhea, and C.
Most oral beta-lactams have poor bioavailability and achieve low serum concentrations , making them poor choices for serious or deep seated infections Amoxicillin has the best bioavailability. No beta-lactam has activity vs MRSA except Ceftaroline , and none have activity vs atypical intracellular organisms i.
Legionella, Mycoplasma, Chlamydia. Beta-lactams exhibit time-dependent killing , meaning that efficacy depends on the amount of time the drug concentration is above the MIC. There is no cross-reactivity between PCN and Aztreonam; however, cross-reactivity between Aztreonam and Ceftazidime has been reported due to an identical side chain.
If skin testing unavailable and beta-lactam is preferred, decision depends on prior type of reaction and how recently it occurred. If probable history of anaphylaxis, desensitize. Drug of choice for Enterococcal infections if susceptible E. Used with aminoglycosides for synergy for Enterococcal endocarditis. Little role for oral ampicillin due to inferior absorption vs Amoxicillin. Dicloxacillin is a reasonable oral choice for non-severe cellulitis; otherwise, for all serious MSSA infections e.
Nafcillin tends to be better tolerated than Oxacillin less hepatitis and rash 4. Caution with Unasyn for polymicrobial intraabdominal infections due to high rate of resistance of E. Only Ceftazidime and Cefepime cover Pseudomonas. Only Cefoxitin and Cefotetan have good anaerobic coverage. Bacteroides fragilis has high rates of resistance to Cefotetan Cefoxitin is a bit better — for serious intrabdominal infections, should use other agents.
Cefotetan can cause elevated INR. Note small but important rate of resistance in Strep pneumo. Ceftriaxone usually once daily dosing g except for meningitis 2 g IV q12 hours. Cefotaxime is more frequent dosing often used preferentially for spontaneous bacterial peritonitis due to good track record and high levels achieved in ascitic fluid, but Ceftriaxone probably equivalent.
Cefpodoxime useful as a step-down to oral after IV Ceftriaxone, but like all beta lactams note poor serum bioavailability so not suitable for bacteremia, deep-seated or serious infections. Ceftriaxone can cause biliary sludging and cholecystitis. Virtually no Gram positive or anaerobic coverage.
Most experts will avoid using Ceftriaxone or Ceftazidime and any lower generation cephalosporin for serious infections due to SPICE organisms, due to concern for inducible resistance from chromosomal beta-lactamase AmpC. For cefepime and ceftriaxone, beware CNS toxicity of encephalopathy, altered mental status, and seizures in the elderly and those with renal failure. Ceftazidime and Cefepime sometimes have activity against certain ESBL producing organisms, but reports of failure in this setting so use with caution.
Great penetration virtually everywhere, including CSF. Other differences of Ertapenem vs other carbapenems is lack of activity vs Acinetobacter and Enterococci. Main advantages:1 No cross-reactivity with PCN allergy except with Ceftazidime — cross-reactivity due to identical side chain and 2 Does not cause renal failure almost no significant toxicity Beware significant rate of resistance of Pseudomonas in most institutions, so empiric double coverage often required.
No ESBL coverage. Most are bacteriostatic, except for Aminoglycosides generally considered cidal due to irreversible binding and disruption of outer cell membrane 1. Azithromycin is the drug of choice for most atypical infections. Erythromycin now used mostly as GI motility agent — prior to endoscopy, or to advance feeding tubes.
Clarithromycin also used for MAC treatment in combination with other drugs. Azithromycin has better H. Side Effects: photosensitivity, GI discomfort, teeth discoloration, inhibits bone growth in children, teratogenic, steatosis and hepatotoxicity.
Doxycycline is the preferred tetracycline in most cases due to convenient BID dosing, and lack of food-drug interactions. Often part of empiric therapy in toxic-appearing patients with fever and rash mainly for Rocky Mountain Spotted Fever. Doxycycline has excellent bioavailability. Also has activity vs PCP combine with primaquine and toxoplasmosis combine with pyrimethamine Beware increasing resistance among Bacteroides — not a good choice for severe intraabdominal infections.
If D-test positive, do not use Clindamycin. Does not penetrate CSF — cannot use for brain abscesses. Traditionally causes highest rate of C. For synergy, best evidence and utility for Enterococcal endocarditis if susceptible.
For Staph prosthetic valve endocarditis, aminoglycoside recommended for 2 weeks with Rifampin. Poor urine and CSF penetration. Aminoglycosides exhibit concentration-dependent killing — more effective with higher peak concentration relative to MIC vs time-dependent killing of beta lactams — more important to maintain levels above MIC Three ways to dose aminoglycosides doses listed for Gentamicin. Check peak after 3rd dose, trough before 4th dose. Turnbaugh, P.
Ley, M. Hamady, C. Fraser-Liggett, R. Knight, and J. The human microbiome impacts of antibiotic utilization in order that project. Nature — we are able to target the infectious agent 3. Kamada ,N. Regulation of beyond adversely affecting patient health.
Gastroenterology rising infectious diseases is that the lack of Eckburg, P. Bik, C. Bernstein, Misuse of antibiotics might cause antibiotic- E. Purdom, L. Dethlefsen, M. Sargent, S. Nelson, and D. Diversity of the human intestinal microbial requirement for mucosal vaccine flora. Science — Suau, A. Bonnet, M. Sutren, J. Godon, are capable of causing both general and G. Gibson, M. Collins, and J. Direct analysis of genes encoding 16S immune system could be a composite and rRNA from complex communities reveals redundant system which provokes extensive many novel molecular species within the quantity of S-IgA beyond cell-mediated human gut.
Backhed, F. Ley, J. Sonnenburg, pathogen penetration and inflammation. Peterson, and J. The mucosal immune system ought to be Host-bacterial mutualism in the human most effective in supporting immunity intestine. Diversity,stabilityand resilience of attenuated pathogens for vaccines purposes. Nature — The unique mucosal vaccines authorized for Gustafsson, B. The physiological mucosal vaccines may involve vaccine importance of the colonic microflora.
The gut flora as a forgotten organ. Wostmann, B. The germfree careful decontamination of the digestive animal in nutritional studies. Nat Rev Immunol. Control of pathogens and pathobionts by the gut microbiota.
Nat Immunol. Barman, M. Unold, K. Shifley, E. Amir, Wells, C. Jechorek, and S. Hung, N. Bos, and N. Evidence for the Enteric salmonellosis disrupts the microbial translocation of Enterococcus faecalis ecology of the murine gastrointestinal tract. Lupp, C. Robertson, M. Wickham, Maddaus, R.
Sekirov, O. Champion, E. Gaynor, Jechorek, and R. Role of and B. Host-mediated intestinal anaerobic bacteria in colonization inflammation disrupts the intestinal resistance. Cell Host Microbe Maddaus, C. Reynolds, R. Jechorek, and R. Stecher, B. Robbiani, A. Walker, A. Role of anaerobic flora M.
Westendorf, M. Barthei, M. Kremer, S. Macpherson, J. Buer, J. Parkhill, G. By using our site, you agree to our collection of information through the use of cookies. To learn more, view our Privacy Policy. To browse Academia. Log in with Facebook Log in with Google.
Remember me on this computer. Enter the email address you signed up with and we'll email you a reset link. Need an account? Click here to sign up. Download Free PDF. Pitambar Khanal.
A short summary of this paper. The first antibiotic marketed is Penicillin in ; soon it got resistance to bacteria. After Penicillin there were several other antibiotics introduced in the market but most of them got resistant to bacteria.
The causes of antibiotic resistance are its underuse, overuse, inappropriate use, extensive agriculture use, and lack of regularity in developing countries. Health and economic impacts are two major consequences of antibiotic resistance we need to face at the present moment. Infections caused by Antibiotic resistance is the condition in which bacteria antibiotic-resistant germs are difficult and sometimes changes in response to treatment with the given impossible to treat.
0コメント