Antibiotics, Antimicrobial Resistance, Antibiotic Susceptibility Testing
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Antibiotics, Antimicrobial Resistance, Antibiotic Susceptibility Testing

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Microbiology and Molecular Diagnosis in Pathology.
© Elsevier Inc.
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Antibiotics, Antimicrobial 
Resistance, Antibiotic 
Susceptibility Testing, 
and Therapeutic Drug 
Monitoring for Selected Drugs
Introduction 120
Introduction to Pharmacokinetics and Pharmacodynamics 122
Beta-Lactams and Cephalosporins 123
Mechanisms of resistance 124
Aminoglycosides 125
Therapeutic drug monitoring of aminoglycosides 127
Vancomycin 128
Therapeutic drug monitoring of vancomycin 130
Mechanism of resistance of aminoglycosides and vancomycin 132
Daptomycin and Linezolid 133
Sulfonamide and Trimethoprim 133
Quinolones 134
Macrolides and Lincosamides 135
Mechanism of resistance and D-test 136
Tetracyclines 136
Carbapenems 137
Mechanisms of resistance 138
Colistin/Polymyxin B 138
Antimycobacterial Agents 139
Other Antibiotics 141
Antifungal Agents 141
Therapeutic drug monitoring of azoles 143
Antibiotic Susceptibility Testing 143
Principles of Antibiotic Susceptibility Testing 144
Antimycobacterial susceptibility testing 145
Antiparasitic Agents 146
Antiviral Agents 147
Key Points 148
References 152
Microbiology and Molecular Diagnosis in Pathology120
Antibiotics represent a diverse group of chemotherapeutic agents with 
activity against microorganisms such as bacteria, fungi, viruses, or proto-
zoa. The word antibiotic comes from Greek words \u201canti\u201d means against 
and \u201cbios\u201d meaning life. Although the original word coined by Selman 
Waksman represented compounds which were derived from microorgan-
isms, many antibiotics currently used in medical practice are also synthetic 
or semisynthetic compounds. The first effective antibiotic penicillin was 
discovered by Sir Alexander Fleming in 1928, but currently more than 
100 antibiotics are approved for medical use worldwide. Antibiotics can 
be classified based on their chemical structures (Table 7.1). Alternatively, 
they can be categorized on the basis of their target specificity. The nar-
row-spectrum antibiotics target particular types of bacteria, such as 
Table 7.1 Classification of antibiotics based on chemical structure
Chemical structure Specific example of drugs
Aminoglycoside Amikacin, gentamicin, kanamycin, neomycin, netilmicin, 
paromomycin, sisomicin, streptomycin, tobramycin
Glycopeptide Vancomycin, teicoplanin
(penicillin and 
related drugs)
Penicillin G, Penicillin V, ampicillin, carbenicillin, 
dicloxacillin, nafcillin, oxacillin, piperacillin, temocillin, 
First generation: Cefadroxil, cefazolin, ceflatonin, cephalexin
Second generation: Cefaclor, cefamandole, cefoxitin, 
cefprozil, cefuroxime
Third generation: Cefixime, cefdinir, cefditoren, 
cefoperazone, cefotaxime, ceftriaxone, ceftizoxime
Fourth generation: Cefepime
Fifth generation: Ceftobiprole
Ertapenem, doripenem, meropenem
Monobactam Aztreonam, imipenem, meropenem, ertapenem
Macrolide Azithromycin, clarithromycin, dirithromycin, erythromycin, 
roxithromycin, troleandomycin, spectinomycin
Polypeptides Bacitracin, colistin, polymyxin B
Oxazolidinones Linezolid, quinupristin/dalfopristin
Quinolones Ciprofloxacin, enoxacin, gatifloxacin, moxifloxacin, 
ofloxacin, norfloxacin, levofloxacin
Sulfonamides Mafenide, sulfacetamide, sulfadiazine, sulfamethoxazole, 
sulfanilamide, sulfisoxazole, trimethoprim
Tetracycline Doxycycline, minocycline, oxytetracycline, tetracycline
Antibiotics, Antimicrobial Resistance, Antibiotic Susceptibility Testing 121
Gram-negative or Gram-positive bacteria, while broad-spectrum antibiot-
ics can be effective against a wide range of bacteria. In addition, antibiotics 
can be either bactericidal or bacteriostatic, based on their mechanism of 
action. Bactericidal agents typically kill bacteria directly, whereas bacterio-
static agents prevent cell growth and division [1,2].
Antibiotics can also be classified on the basis of their mechanism of 
action. There are six major mechanisms by which an antibiotic exerts its 
pharmacological action. These include:
\u25cf Inhibition of cell wall synthesis.
\u25cf Inhibition of bacterial protein synthesis.
\u25cf Disruption of the bacterial cell membrane.
\u25cf Damage to bacterial cell membrane.
\u25cf Inhibition of bacterial nucleic acid synthesis.
\u25cf Antimetabolite activities.
Inhibition of bacterial cell wall formation is probably the most com-
mon mechanism by which an antibiotic kills bacteria or inhibits bacterial 
growth. Antibiotics which interfere with cell wall synthesis are beta-lactam 
antibiotics (penicillin and related antibiotics), cephalosporins, vancomycin, 
etc., while antibiotic such as clindamycin, chloramphenicol, lincomycin, 
and macrolide antibiotics interferes with protein synthesis of bacteria by 
binding to the 50S ribosomal unit. Antibiotics that interfere with bacterial 
protein synthesis by binding to the 30S ribosomal unit are tetracycline and 
aminoglycosides. Sulfonamides and trimethoprim kills bacteria by inhib-
iting folate synthesis. Antibacterial effect of metronidazole, quinolones, 
and novobiocin is due to their capability of interfering with bacterial 
DNA synthesis while rifampin interferes with bacterial RNA synthesis. 
Polymyxin B kills bacteria by interfering with cell membrane function. 
In Table 7.2, antibiotics are classified based on their mechanism of action.
Table 7.2 Mechanism by which antibiotics kill bacteria
Mechanism Examples of antibiotic
Inhibition of bacterial cell wall 
Vancomycin, cephalosporins, beta-lactam 
antibiotics (including semisynthetic drugs)
Inhibition of bacterial protein 
Aminoglycosides, chloramphenicol, 
macrolide antibiotics, tetracycline
Disrupting bacterial cell membrane Bacitracin
Damaging bacterial cell membrane Polymyxin B
Inhibition of bacterial nucleic acid 
Quinolones, metronidazole, rifampin
Antimetabolite activity Sulfonamides, dapsone, trimethoprim
Microbiology and Molecular Diagnosis in Pathology122
When a drug is administered orally it undergoes several steps in the body 
that determine concentration of that drug in serum/plasma or whole 
blood. These steps include liberation (release of drug from binders) of 
the drug, absorption from gastrointestinal tract, distribution of the drug 
in target organ, protein binding of the drug, metabolism (hepatic or non-
hepatic metabolism), and elimination. Although many drugs are excreted 
in the urine, some drugs are also excreted through bile. Basic pharmacoki-
netics has been discussed in detail in pharmacology textbooks. Therefore, 
only a brief discussion of this important topic is presented in this 
chapter. Liberation of a drug after oral administration depends on the for-
mulation of the dosage. Immediate release formulation releases the drugs 
at once from the dosage form when administered, while the same drug 
may also be available in sustained release formulation. Absorption of a 
drug depends on the route of administration. Generally, an oral admin-
istration is the route of choice but certain drugs must be administered 
intravenously or intramuscularly if the drug has poor oral bioavailability, 
or is destroyed by gastric acid or undergoes extensive first pass metabo-
lism. When a drug enters the blood circulation, it is distributed throughout 
the body into various tissues and the pharmacokinetic parameter is called 
volume of distribution (Vd). This is the hypothetical volume to account 
for all drugs in the body and is also termed as the apparent volume of 
 Vd Dose/Plasma concentration of drug=
The amount of a drug that interacts with the receptor or