Essentials of Medical Microbiology: Antimicrobial Agents and Resistance (PDF)

General Bacteriology: Chapter Antimicrobial Agents and Antimicrobial Resistance 3.5...

General Bacteriology: Chapter Antimicrobial Agents and Antimicrobial Resistance 3.5 Chapter Preview „„Antimicrobial Agents zzAcquired and Intrinsic zzMechanism of Resistance „„Antimicrobial Resistance zzMutational and Transferable ANTIMICROBIAL AGENTS Antimicrobials are the agents that kill or inhibit the growth of microorganisms. Classification Antimicrobial agents are classified in various ways: 1. According to microorganisms against which they are used—antibacterial, antifungal, antiparasitic, antiviral agents. Only antibacterial agents are discussed here. 2. According to their ability to kill (ends with suffix cidal) or inhibit (ends with suffix static) the microorganism, e.g. bactericidal and bacteriostatic 3. According to the source: „„ Antibiotics: These are natural substances, produced by certain groups of microorganisms „„ Chemotherapeutic agents: These agents are chemically synthesized. Note: Since many antibiotics and their analogues are now Fig. 3.5.1: Mechanism of action of antimicrobial agents. synthesized, antibiotics and chemotherapeutic agents Acquired Resistance are no more distinct terminologies. Therefore they should be addressed as a single entity, ‘antimicrobial agents’ This refers to the emergence of resistance in bacteria that are 4. According to their site of action and usage: ordinarily susceptible to antimicrobial agents, by acquiring „„ Disinfectants destroy a wide range of microbes on the genes coding for resistance. Most of the antimicrobial non-living surfaces to prevent their spread resistance shown by bacteria belong to this category. „„ Antiseptics (which are applied to the living tissues The emergence of resistance is a major problem and help to reduce infection), and worldwide in antimicrobial therapy. Infections caused „„ Antibiotics (which destroy microorganisms within by resistant microorganisms often fail to respond to the the body). standard treatment, resulting in prolonged illness, higher 5. According to the chemical structure and mechanism of healthcare expenditures, and a greater risk of death. ™™ Overuse and misuse of antimicrobial agents is the single action—the antimicrobial agents can be further divided into many classes, as described in Fig. 3.5.1 and Table 3.5.1. most important cause of development of acquired Though incorrect, the word ‘antibiotics’ is loosely used to resistance ™™ The evolution of resistant strains is a natural phenomenon, describe antimicrobial agents. which can occur among bacteria especially when an antibiotic is overused ANTIMICROBIAL RESISTANCE ™™ Use of a particular antibiotic poses selective pressure in a Antimicrobial resistance refers to development of population of bacteria which in turn promotes resistant resistance to an antimicrobial agent by a microorganism. bacteria to thrive and the susceptible bacteria to die off It can be of two types—acquired and intrinsic. (Fig. 3.5.2) 62 Section 1  General Microbiology Table 3.5.1: Antimicrobial agents—classification, indication, and mechanism of resistance. Class/mechanism Drugs Spectrum of activity Mechanism of resistance A. Inhibit Cell Wall Synthesis β-Lactam Antibiotics (Bactericidal: block peptidoglycan cross linking by inhibiting the transpeptidase enzyme, i.e. penicillin-binding protein) Penicillins Penicillin Penicillin G Mostly gram-positive bacteria: 1. Drug inactivation (by Aqueous penicillin G Streptococcus pyogenes producing β-lactamase Procaine penicillin G Pneumococcus enzyme): Seen in both Benzathine penicillin G Corynebacterium diphtheriae (diphtheria) gram-positive and gram- Penicillin V Clostridium tetani (tetanus) negative bacteria Clostridium perfringens (gas gangrene) 2. Alteration of target site- Meningococcal infection PBP (penicillin-binding Gonococcus (resistance has been reported) protein) is altered to PBP2a, Treponema pallidum (syphilis) seen in gram-positive Penicillinase-resistant- Cloxacillin, dicloxacillin, Same as penicillin plus bacteria penicillins flucloxacillin, nafcillin, Penicillinase producing Staphylococcus aureus 3. Decreased permeability oxacillin and methicillin as in gram-negative bacteria- due to altered Aminopenicillins Ampicillin Same as penicillin plus outer-membrane porins (extended spectrum) Amoxicillin Enterococcus faecalis Escherichia coli Helicobacter pylori Salmonella (resistance reported) Shigella (bacillary dysentery) Antipseudomonal Carbenicillin, Same as aminopenicillins plus penicillins Ticarcillin, piperacillin Pseudomonas aeruginosa Cephalosporins 1st generation Cefazolin Staphylococcus aureus Cephalexin Staphylococcus epidermidis Some gram-negative bacteria like Escherichia coli and Klebsiella 2nd generation Cefoxitin, cefotetan Same as 1st generation plus Cefaclor, Cefuroxime ↑ Gram-negative activity ↑ Anaerobic activity (cefoxitin and cefotetan) 3rd generation Ceftriaxone Decreased activity against gram-positives Cefotaxime compared to 1st, 2nd generations ESBL (extended spectrum Ceftazidime ↑ Gram-negative activity β-lactamases) Some are active against Pseudomonas (Ceftazidime) Ceftriaxone is active against pneumococci, meningococci and MSSA. 4th generation Cefepime Good activity against gram-positive and Cefpirome negative bacteria including Pseudomonas 5th generation Ceftobiprole Same as 4th generation and MRSA (only Ceftaroline β-lactam to be effective against MRSA) β lactam + β lactamase Ampicillin-sulbactam* Same as spectrum of respective β-lactam drug inhibitors Amoxicillin-clavulanate* plus active against β-lactamase producing Cefoperazone-sulbactam bacteria Ceftazidime-avibactam *Have excellent anaerobic coverage Ceftolozane-tazobactam Piperacillin-tazobactam* Meropenem- vaborbactam* Carbapenems Imipenem Broadest range of activity against most 1. Produce carbapenemases Meropenem bacteria, which include gram-positive cocci, 2. Efflux pump Doripenem Enterobacteriaceae, Pseudomonas, Listeria, Ertapenem anaerobes like Bacteroides fragilis and Clostridioides difficile No action on MRSA and Mycoplasma Contd…  Chapter 3.5  General Bacteriology: Antimicrobial Agents and Antimicrobial Resistance 63 Contd… Class/mechanism Drugs Spectrum of activity Mechanism of resistance Monobactam Aztreonam Gram-negative rods ESBL Other cell wall inhibitors Glycopeptides Vancomycin Active against most gram-positive bacteria Alteration of target (bactericidal: disrupt Teicoplanin including MRSA (drug of choice), and for (substitution of D-alanine— peptidoglycan cross-linkage) Clostridioides difficile infection (CDI) D-alanine side chain of peptidoglycan) Fosfomycin Fosfomycin Inactivates the enzyme UDP-N- 1. Alteration of target acetylglucosamine-3-enolpyruvyltransferase, also 2. Producing enzymes that known as MurA; required for cell wall synthesis. inactivates fosfomycin Active against urinary tract pathogens; against both gram-positive and gram-negative bacteria such as Enterococcus faecalis, Escherichia coli, etc. Bacitracin Bacitracin Topical gram-positive cocci infections Not defined B. Protein Synthesis Inhibition Anti-30S ribosomal subunit Aminoglycosides Gentamicin Aerobic gram-negative bacteria, such as— 1. Drug inactivation by (bactericidal: irreversible Neomycin Enterobacteriaceae and some are active against aminoglycoside-modifying binding to 30S) Amikacin Pseudomonas (gentamicin and amikacin) enzyme Tobramycin Often used for empirical therapy in adjunct with 2. Decreased permeability Streptomycin third generation cephalosporins in respiratory through gram-negative infections, meningitis and subacute bacterial outer membrane endocarditis 3. Decreased influx of drug Tetracyclines Tetracycline Rickettsiae, Chlamydiae, Mycoplasma, 1. Decreased intracellular (bacteriostatic: bind to 30S Doxycycline Spirochetes drug accumulation (active subunit of ribosome and Minocycline Yersinia pestis, Brucella, Haemophilus ducreyi, efflux) block tRNA attachment) Demeclocycline Campylobacter, Vibrio cholerae 2. Ribosomal target site alteration Glycylglycines Tigecycline Staphylococcus, Enterococcus Active drug efflux pump (MOA, same as tetracycline) Acinetobacter, and E. coli Anti-50S ribosomal subunit Chloramphenicol Chloramphenicol Haemophilus influenzae 1. Drug inactivation by (bacteriostatic: binds to Pyogenic meningitis producing chloramphenicol 50S ribosomal subunit and Brain abscess acetyltransferase enzyme interfere with peptide bond Anaerobic infection 2. Altered membrane formation) Enteric fever (Salmonella)—not used now due to transport (active efflux) development of resistance Macrolides Erythromycin Streptococcus 1. Alteration of ribosomal (bacteriostatic: binds 50S Azithromycin Haemophilus influenzae target ribosomal subunit and Clarithromycin Mycoplasma pneumoniae 2. Active efflux of antibiotic prevent translocation of elongated peptide) Ketolide Telithromycin Community acquired pneumonia (mild to Altered target (methylation of (MOA, same as macrolide) moderate) by S. pneumoniae ribosomal binding site) Active drug efflux Lincosamides Clindamycin S. aureus (CA-MRSA, MSSA) Altered target (methylation of (binds 50S subunit, blocks Lincomycin Beta hemolytic streptococci ribosomal binding site) peptide bond formation) Actinomyces, Arcanobacter, Capnocytophaga Anaerobic infection Oxazolidinones Linezolid Resistant gram-positives like MRSA Alteration of target site (Inhibitit protein synthesis by binding to 50S) Streptogramins Quinupristin Streptococcus pyogenes and Staphylococcus 1. Alteration of target (Inhibit protein synthesis by Dalfopristin aureus skin infections (dalfopristin) binding to 50S) MRSA infections 2. Active efflux (quinupristin) VRE (Vancomycin resistant enterococci) 3. Drug inactivation infections (quinupristin and dalfopristin) Contd… 64 Section 1  General Microbiology Contd… Class/mechanism Drugs Spectrum of activity Mechanism of resistance Mupirocin Mupirocin Topical ointment is given for- Mutation of gene for target (Inhibits isoleucyl-tRNA Skin infections site protein synthetase) Nasal carriers of MRSA Fusidane Fusidic acid S. aureus (oral and topical use) Altered target (Prevents the turnover of elongation factor G from the ribosome) C. Nucleic Acid Synthesis Inhibitors DNA synthesis inhibitors Fluoroquinolones Inhibit DNA gyrase (A subunit) and topoisomerase IV, thus inhibiting DNA synthesis Nalidixic acid Coliform gram-negative bacilli 1. Alteration of target Fluoroquinolones Norfloxacin, ciprofloxacin, Enterobacteriaceae: such as E. coli, Klebsiella, (mutation of DNA gyrase 1st generation ofloxacin Enterobacter, Salmonella, Shigella, Proteus, Yersinia genes) 2. Poor transport across cell Fluoroquinolones Levofloxacin, lomefloxacin, Others: Neisseria, Haemophilus, Campylobacter, Vibrio cholerae, Pseudomonas, Staphylococcus membrane 2nd generation moxifloxacin, sparfloxacin aureus Nitroimidazoles Metronidazole, tinidazole Anaerobic organisms 1. Decreased drug uptake (Damage DNA) secnidazole Also active against protozoa such as Entamoeba, 2. Active efflux Giardia and Trichomonas 3. Decreased drug activation Nitrofuran Nitrofurantoin Urinary tract infection Altered drug activating (Damages bacterial DNA) (E. coli, Klebsiella, Enterococcus) enzyme RNA synthesis inhibitors Rifamycins Rifampicin, rifaximin M. tuberculosis, M. leprae Alteration of target (mutation (Inhibits RNA polymerase) Nontuberculous mycobacteria of rpoB gene) Staphylococcus aureus Prophylaxis for H. influenzae meningitis Prophylaxis for meningococcal meningitis D. Mycolic Acid Synthesis Inhibitors Isonicotinic acid hydrazide Isoniazid (INH) Tuberculosis Mutations in enzyme (Inhibits mycolic acid Latent TB processing isoniazid into active synthesis) metabolites (KatG enzyme) E. Folic acid Synthesis Inhibitors Bacteriostatic: Competitively inhibit enzymes involved in two steps of folic acid biosynthesis Folate synthase Dihydrofolate reductase PABA (para-amino-benzoic acid) Sulfonamide blocks Dihydrofolic acid Trimethoprim blocks Tetrahydrofolic acid Antifolates Sulfadiazine Sulfadiazine: Production of insensitive (Sulfonamides and Sulfacetamide Used topically in burn wound surface targets [dihydropteroate trimethoprim) Co-trimoxazole Co-trimoxazole is indicated in: synthetase (sulfonamides) (Trimethoprim + Urinary tract and respiratory tract infections- and dihydrofolate reductase Sulfamethoxazole) Active against Serratia, Klebsiella, Enterobacter (trimethoprim)] that bypass Shigella dysentery, Vibrio cholerae metabolic block Toxoplasma gondii, Haemophilus ducreyi Pneumocystis jirovecii F. Antimicrobial agents that act on cell membrane Gramicidin Topical use against cocci (gram-positive and Not defined (Forms pores) negative) Lipopeptides Daptomycin Bactericidal against gram-positive bacteria Not defined (Forms channel in cell including VRE and MRSA membrane, leading to leakage) Polymyxins Polymyxin B Gram-negative infections 1. Alteration of LPS (Binds to LPS and disrupt Colistin or Polymyxin E 2. Efflux pump mediated both outer and inner cell (systemic and inhalational membrane) use) Abbreviations: MSSA, methicillin sensitive Staphylococcus aureus; MRSA, methicillin resistant Staphylococcus aureus; CA-MRSA, community acquired MRSA; ESBL, extended spectrum β-lactamases; VRE, vancomycin resistant Enterococcus.  Chapter 3.5  General Bacteriology: Antimicrobial Agents and Antimicrobial Resistance 65 ™™ Mutational drug resistance differs from transferable drug resistance in many ways (Table 3.5.3) ™™ Usually, it is a low level resistance, developed to one drug at a time; which can be overcome by using combination of different classes of drugs ™™ That is why multidrug therapy is used in tuberculosis using 4–5 different classes of drugs, such as isoniazid, rifampicin, pyrazinamide, ethambutol and streptomycin. Transferrable Drug Resistance In contrast, transferrable drug resistance is plasmid coded and usually transferred by conjugation or rarely by transduction, or transformation (refer Chapter 3.4). ™™ The resistance coded plasmid (called R plasmid) can carry multiple genes, each coding for resistance to one class of antibiotic ™™ Thus, it results in a high degree of resistance to multiple drugs, which cannot be overcome by using combination Fig. 3.5.2: Mechanism of development of acquired resistance. of drugs. ™™ Thus the resistant bacterial populations flourish in areas Mechanism of Antimicrobial Resistance of high antimicrobial use, where they enjoy a selective advantage over susceptible populations Bacteria develop antimicrobial resistance by several ™™ The resistant strains then spread in the environment mechanisms. and transfer the genes coding for resistance to other 1. Decreased Permeability across the Cell Wall unrelated bacteria. Other factors favouring the spread of antimicrobial Certain bacteria modify their cell membrane porin resistance include— channels; either in their frequency, size, or selectivity; ™™ Poor infection control practices in hospitals, e.g. poor thereby preventing the antimicrobials from entering into hand hygiene practices can facilitate the transmission the cell. This resistance mechanism has been observed of resistant strains in many gram-negative bacteria, such as Pseudomonas, ™™ Inadequate sanitary conditions Enterobacter and Klebsiella species against drugs, such as ™™ Inappropriate food-handling imipenem, aminoglycosides and quinolones. ™™ Irrational use of antibiotics by doctors, not following 2. Efflux Pumps antimicrobial susceptibility report ™™ Uncontrolled sale of antibiotics over the counters without Certain bacteria possess efflux pumps which mediate prescription. expulsion of the drug(s) from the cell, soon after their entry; thereby preventing the intracellular accumulation of drugs. Intrinsic Resistance This strategy has been observed in: It refers to the innate ability of a bacterium to resist a class ™™ Escherichia coli and other Enterobacteriaceae against of antimicrobial agents due to its inherent structural or tetracyclines, chloramphenicol functional characteristics, (e.g. gram-negative bacteria are ™™ Staphylococci against macrolides and streptogramins resistant to vancomycin). This imposes negligible threat as ™™ Staphylococcus aureus and Streptococcus pneumoniae it is a defined pattern of resistance and is non-transferable. against fluoroquinolones. However, the clinicians must be aware so as to exclude these antibiotics from therapy (Table 3.5.2). 3. By Enzymatic Inactivation Certain bacteria can inactivate the antimicrobial agents by Mutational and Transferable Drug Resistance producing various enzymes, such as: In presence of selective antibiotic pressure, bacteria ™™ β-lactamase enzyme production (observed in both acquire new genes mainly by two broad methods: gram-positive and gram-negative bacteria): It breaks down the β-lactam rings, thereby inactivating the Mutational Resistance β-lactam antibiotics (see the highlight box) Resistance can develop due to mutation of the resident ™™ Aminoglycoside modifying enzymes like (acetyltrans- genes. ferases, adenyltransferases, and phosphotransferases, ™™ It is typically seen in Mycobacterium tuberculosis, produced by both gram-negative and gram-positive bac- developing resistance to anti-tubercular drugs teria)—they destroy the structure of aminoglycosides 66 Section 1  General Microbiology Table 3.5.2: Intrinsic antimicrobial resistance. Organisms Intrinsic resistance to the following antimicrobial agents Enterobacteriaceae Members of family Enterobacteriaceae are intrinsically resistant to antimicrobials specific for gram-positive organisms such as: clindamycin, daptomycin, fusidic acid, glycopeptides (vancomycin), lipoglycopeptides (oritavancin, teicoplanin, and telavancin), linezolid, tedizolid, quinupristin-dalfopristin, rifampin, and macrolides (erythromycin, clarithromycin, and azithromycin) Exceptions: Salmonella and Shigella spp. are susceptible azithromycin Klebsiella pneumoniae Same as for Enterobacteriaceae plus ampicillin and ticarcillin Citrobactér species Same as for Enterobacteriaceae plus ampicillin, first and second generation cephalosporins, cephamycins, amoxicillin-clavulanate and ampicillin-sulbactam Enterobacter species Same as for Enterobacteriaceae plus ampicillin, first generation cephalosporins, cephamycins, amoxicillin- clavulanate and ampicillin-sulbactam Proteeae tribe Same as for Enterobacteriaceae plus ampicillin, first and second generation cephalosporins, tetracyclines, tigecycline, nitrofurantoin and polymyxins (polymyxin B and polymyxin E or colistin) Salmonella species Same as for Enterobacteriaceae plus aminoglycosides, first and second generation cephalosporins Shigella species Same as for Enterobacteriaceae plus aminoglycosides, first and second generation cephalosporins, and cephamycins Serratia marcescens Same as for Enterobacteriaceae plus ampicillin, first and second generation cephalosporins, cephamycins, amoxicillin-clavulanate, ampicillin-sulbactam, nitrofurantoin and polymyxins (Polymyxin B and colistin) Yersinia enterocolitica Same as for Enterobacteriaceae plus ampicillin, ticarcillin, first generation cephalosporins and amoxicillin- clavulanate Non-fermentative gram- Non-fermentative gram-negative bacteria are intrinsically resistant to penicillin (i.e., benzyl penicillin), first negative bacteria and second generation cephalosporins, cephamycins, clindamycin, daptomycin, fusidic acid, glycopeptides (NF-GNB) (vancomycin), linezolid, macrolides, quinupristin-dalfopristin, and rifampin Pseudomonas Same as for NF-GNB, plus ampicillin, ceftriaxone, amoxicillin-clavulanate, ampicillin-sulbactam, Ertapenem, aeruginosa tetracyclines, tigecycline, co-trimoxazole and chloramphenicol Acinetobacter Same as for NF-GNB, plus ampicillin, amoxicillin, amoxicillin-clavulanate, ertapenem, aztreonam, baumannii chloramphenicol and fosfomycin Stenotrophomonas Same as for NF-GNB, plus ampicillin, amoxicillin, cefotaxime, ceftriaxone, cefepime, amoxicillin-clavulanate, maltophilia aztreonam, imipenem, meropenem, ertapenem, polymyxins (polymyxin B and colistin), aminoglycosides, chloramphenicol and fosfomycin Burkholderia cepacia Same as for NF-GNB, plus ampicillin, amoxicillin, ampicillin-sulbactam, amoxicillin-clavulanate, ertapenem, complex polymyxins (polymyxin B and colistin) and fosfomycin Gram-positive bacteria Gram-positive bacteria are intrinsically resistant to aztreonam, polymyxin B/colistin, and nalidixic acid S. aureus Same as for other gram-positive bacteria Enterococcus species Same as for other gram-positive bacteria plus cephalosporins, aminoglycosides*, clindamycin and co- trimoxazole. E. gallinarum and E. casseliflavus are intrinsically resistant to vancomycin, in addition. *Aminoglycosides such as gentamicin are effective against Enterococcus, when given along with cell-wall acting drugs like penicillin, ampicillin or vancomycin, due to synergistic effect (Chapter 76). Table 3.5.3: Mutational vs transferable drug resistance. 4. By Modifying the Target Sites Mutational drug resistance Transferable drug resistance Modification in the target sites of antimicrobial agent (which Resistance to one drug at a Multiple drugs resistance at the are within the bacteria) is a very important mechanism. It time same time is observed in: Low-degree resistance High-degree resistance ™™ MRSA (Methicillin-resistant Staphylococcus aureus): Resistance can be overcome Cannot be overcome by drug In these strains, the target site of penicillin i.e. penicillin by combination of drugs combinations binding protein (PBP) gets altered to PBP-2a. The altered Virulence of resistance Virulence not decreased PBP coded by a chromosomally coded gene mec A, do mutants may be lowered not sufficiently bind to β-lactam antibiotics and therefore Resistance is not transferable Resistance is transferable to other prevent them from inhibiting the cell wall synthesis. to other organisms organisms (Described in detail in Chapter 51) Spread to off-springs by Spread by: Horizontal spread ™™ β-lactam resistance in pneumococci is due to alteration vertical spread only (conjugation, or rarely by of PBP to PBP2b. transduction/transformation) ™™ Streptomycin resistance in Mycobacterium tuberculo- sis is due to modification of ribosomal proteins or 16S ™™ Chloramphenicol acetyl transferase: It is produced by rRNA members of Enterobacteriaceae; it destroys the structure ™™ Rifampicin resistance in Mycobacterium tuberculosis— of chloramphenicol. due to mutations in RNA polymerase  Chapter 3.5  General Bacteriology: Antimicrobial Agents and Antimicrobial Resistance 67 ™™ Quinolone resistance seen in many gram-positive Contd... bacteria, particularly S. aureus and S. pneumoniae— due and 3rd generation cephalosporins and monobactams; how- to mutations in DNA gyrase enzyme. ever remain sensitive to carbapenems and cephamycins. ™™ Vancomycin resistance in enterococci (VRE): These The resistance can be overcome by use of β-lactam along strains have a change in the target site of vancomycin with β-lactamase inhibitor (e.g. sulbactum or clavulanic (i.e. D-alanine D-alanine side chain of peptidoglycan) acid) (Chapter 76). ‰‰ AmpC beta-lactamases: In addition to the antibiotics to which ESBL producers are resistant, AmpC beta-lactamase Beta-lactamase Enzymes producers are resistant to cephamycins (e.g.cefoxitin β-lactamase enzymes are capable of hydrolyzing the β- and cefotetan). But they are sensitive to carbapenems. lactam rings (the active site) of β-lactam antibiotics; thereby Resistance cannot be overcome by β-lactam + β-lactamase deactivating their antibacterial properties. inhibitor combination (BL/BLI) ‰‰ They can be produced by both gram-positive and gram- ‰‰ Carbapenamases: These organisms are resistant to negative organisms all those antibiotics to which AmpC beta-lactamase ‰‰ They are plasmid coded, and transferred from one bacterium producers are resistant. In addition, they are also resistant to other mostly by conjugation, (except in Staphylococcus to carbapenems. Resistance cannot be overcome by BL/BLI. aureus where they are transferred by transduction). Important carbapenemase enzymes are: ¾¾ Klebsiella pneumoniae carbapenemase (KPC) Beta-lactamases are of various types: ¾¾ New Delhi metallo-beta-lactamase (NDM) ‰‰ Extended spectrum β-lactamases (ESBL): Organisms pro- Routine detection of β-lactamase enzymes in the laboratory ducing ESBL enzymes are resistant to all penicillins, 1st, 2nd is not necessary, as it does not play a vital role in deciding the treatment. It is only necessary for epidemiological purposes. Contd... EXPECTED QUESTIONS I. Write short notes on: 5. All of the following are examples of intrinsic 1. Mechanism of antibiotic resistance. antimicrobial resistance, except: 2. Mutational and transferable drug resistance. a. Anaerobic bacteria-aminoglycosides 3. Antimicrobial susceptibility testing method. b. Pseudomonas- carbapenems II. Multiple Choice Questions (MCQs): c. Aerobic bacteria-metronidazole 1. MRSA is mediated due to d. Gram-negative bacteria-vancomycin a. Plasmid b. mecA gene 6. Extended spectrum β-lactamases (ESBL) produc- c. Transposons d. None ing organisms are resistant to all, except: 2. All of the following antimicrobial agents act on a. All penicillins cell membrane, except: b. 3rd generation cephalosporins a. Gramicidin b. Daptomycin c. Monobactam c. Polymyxins d. Vancomycin d. Carbapenems 3. Fosfomycin—all are true, except: 7. All of the following can be given for the treatment a. Inactivates the enzyme MurA of Extended spectrum β-lactamases (ESBL) pro- b. Active against urinary tract pathogens ducing organisms, except: c. Active against both gram-positive and gram- a. Carbapenems negative bacteria b. β-lactam/ lactamase inhibitor combination d. Resistance has not been reported yet c. 3rd generation cephalosporins 4. All of the following antimicrobial agents act on d. Aminoglycoside 50S ribosomal subunit, except: 8. Which of the following can be given for the treat­ a. Aminoglycosides ment of carbapenamase producing organisms? b. Macrolides a. Carbapenems c. Streptogramins b. β-lactam/lactam inhibitor combination d. Chloramphenicol c. 3rd generation cephalosporins d. Aminoglycoside Answers 1. b 2. d 3. d 4. a 5. b 6. d 7. c 8. d