Clinical Use of Antimicrobial

Agents

Xu Lu
The Third People's Hospital of Zheng Jiang
 MAIN CONTENTS

Definition and Classification

Principles of clinical application

 Definition
Antimicrobial Agents:
Drugs with bactericidal or antibacterial
activity, including various antibiotics,
sulfanilamide, imidazoles, nitroimidazoles,
quinolones and other chemical synthesis drugs.
• Bacteriostatic agents: Antibacterial agents that
inhibit the growth or reproduction of bacteria
without killing them.

• Bactericidal agents: Antibacterial agents that kill

bacteria.
• Antimicrobial activity: Ability of antimicrobial
drugs to inhibit or kill pathogenic microorganisms.

• Minimum inhibitory concentration (MIC):

A minimum concentration that inhibits bacterial
growth in the medium.
• Minimum bactericidal concentration (MBC):
A minimum concentration that kills bacterial in the
medium.
• Antibacterial spectrum: range of antimicrobial
agents. (Broad-spectrum antibiotics and narrow-
spectrum antibiotics)

• Post antibiotic effect (PAE) : After the bacteria

were briefly exposed to antibiotics, the
concentration of antibiotics dropped below MIC
or disappeared, and the growth of bacteria
continued to be inhibited.
 Table 1 Main Classification
classification representatives
penicillins penicillin G, amoxicillin

cephalosporins cefalexin，cefuroxime，ceftriaxone
β-lactams
atypical β-lactams cefoxitin, latamoxef, aztreonam, imipenem
β- lactamase inhibitors and compound
clavulinic acid, amoxicillin/clavulinic acid
preparations
aminoglycosides streptomycin amikacin
first generation nalidixic acid
second generation pipemidic acid
quinolones
third generation(fluoroquinolones) levofloxacin, norfloxacin
fourth generation gatifloxacin
macrolides azithromycin, roxithromycin
tetracyclines doxycycline
glycopeptides vancomycin
nitroimidazoles metronidazole
sulfonamides sulfamethoxazole

antifungals amphotericin B, fluconazole, voriconazole

others lincomycin, polymyxin

Principles of clinical application
The only indication for the use of
antimicrobial agents: Bacterial infection!
①Antimicrobial agents are effective in treating bacterial
and fungal infections.
②Cases of preventive application:
Prophylactic in the perioperative period of surgery,
cholera contacts and lack of granulocyte.
③Cases that should not use antimicrobial agents:
Common cold, measles, chicken pox and other viral
diseases
Coma, shock, poisoning, heart failure, tumor, patients
who are using adrenal corticosteroids
Indwelling catheters, indwelling deep venous catheters
and artificial airways which were established
Make right medication regimen
(1)The precondition is to confirm the infection site and
type.

Infection positions:
Skin, respiratory tract, urinary tract, abdominal cavity,
blood, nervous system and so on.

Infection types:
Community-acquired infection and hospital infection.
(2)Know pathogenic species and its sensitivity

Method: Before using antimicrobial agents, collect

corresponding specimens to do etiological examinations,
including pathogen detection and drug sensitive test.
If the patient is in a critical condition, doctors can
start empiric therapy according to the disease situation, the
primary lesions, the basic diseases and the local bacterial
resistance. But remenber to do etiological examinations at
the same time. Once we get the results of examinations, we
should adjust the regimen refer to the results.
Make rational medication regimen based on
pharmaceutical characteristics and drug
adverse reaction(ADR)
BODY

drug
Antimicrobial resistance pathogenic
Agents antibacterial microorganism
activity
• Pharmacokinetics(PK)
Absorption, distribution, and elimination of antimicrobial
agents in the body.

• Pharmacodynamics(PD)
The relationship between blood concentration and
pharmacology or toxicology, including the relationship
between blood concentration and antibacterial activity.

• We can make safer and more reseanable clinical

medication regimen because of PK/PD, which
reflects the change of antibacterial action with
time.
• According to PK/PD, antimicrobial agents are
divided into concentration-dependent and time-
dependent antibacterial agents.

Table 2 antimicrobial agents application according to PK/PD

classification PK/PD typical drugs

penicillins, cephalosporins, aztreonam,

carbapenems, most macrolides, clindamycin,
time dependence(short PAE) T>MIC
fluorine cytosine

streptogramin, tetracycline, vancomycin,

time dependence(long PAE) AUC0-24/MIC teicoplanin, fluconazole, azithromycin,
linezolid

aminoglycosides, fluoroquinolones,
AUC0-24/MIC or
concentration dependence daptomycin, metronidazole, amphotericin B,
Cmax/MIC
echinocandin
 Pharmaceutical characteristics of several
typical antibacterial agents
1.Penicillins

 Penicillin G was the first one to be used clinically. It is

used for the treatment of gram-positive cocci(except
staphylococcus) infection, neisseria infection, syphilis,
leptospirosis, gas gangrene and anthrax.

 Enzyme resistant penicillins such as benzoxicillin and

fluxoxicillin, are used for the infection of staphylococcus
which produces enzyme.
2.Cephalosporins

 The first generation: Cefazolin, cefradine, cefathiamidine,

cefalexin…
High antibacterial activity against staphylococcus, escherichia
coli, proteus, salmonella typhi, shigella, haemophilus influenzae.

 The second generation: cefuroxime, cefotiam, cefaclor, cefazolin

propylene…
The antibacterial spectrum is wider than the first generation.
They can treat various infections caused by sensitive gram-
positive bacteria and gram-negative bacteria.
 The third generation: More stable for β-lactamase
They are also used in the treatment of infections caused by
sensitive gram-positive bacteria and gram-negative bacteria,
but the effect is poorer than the first and second generation.

Cefotaxime: Clinical commonly used

Ceftriaxone: Half life is 6-9 hours, one single dose a day
Ceftazidime: strongest activity of anti - pseudomonas
aeruginosa in the third generation
 The fourth generation: Cefepime, cefoselis…

Stable for cephalosporin enzyme

Activity of anti - pseudomonas aeruginosa
Not stable for extended-spectrum beta-lactamase(ESBL)
3. Atypical β-lactams

• Cephamycin: Cefoxitin, cefmetazole…

Quite stable for β-lactamase

The antibacterial spectrum is similar to the second generation.
Affect blood coagulation
One severe ADR: Disulfiram-like reaction
Disulfiram-like reaction:
Alcohol consumption can cause weakness, dizziness,
drowsiness, hallucinations, body flushing, headache,
nausea, vomiting, decreased blood pressure, and even
shock after taking the drug.
Drugs: Cefmetazole, cefamandole, cefoperazone,
cefmenoxime, cefotiam, latamoxef…

×
• Oxacephems: Latamoxef, flomoxef
Similar to the third generation
Good activity for anaerobic bacteria

• Monobactam: Aztreonam
Narrow-spectrum
The treatment of various negative bacteria
4.Aminoglycosides
Common characteristics:
①stable, good solubility in water, strong effect in alkaline
environment
② wide antibacterial spectrum, bactericidal agents
③ poor gastrointestinal absorption, injection, excreted by the
kidney as a prototype
④ nephrotoxicity, ototoxic
⑤ part of the resistance or complete cross resistance
⑥ synergistic bactericidal effect when combined use of
penicillins or cephalosporins
5.Quinolones
Fluoroquinolones(the third generation):
norfloxacin, ofloxacin, ciprofloxacin

fluorine atom in the structure

good antibacterial activity against gram-positive bacteria and gram-
negative bacteria
low incidence of adverse drug reactions
pregnant women, breast feeding women and newborn with caution.
6.Macrolides: Azithromycin, clarithromycin, roxithromycin…
①stable for gastric acid
② long half life
③ high tissue concentration
④ wider antibacterial spectrum and beter antimicrobial activity
after structural modification
⑤ good PAE
⑥ Less adverse drug reactions
7. Glycopeptides: Vancomycin, norvancomycin, teicoplanin

Treatment of infections caused by resistant gram-positive bacteria,

especially methicillin-resistant staphylococcus aureus(MRSA),
methicillin resistant coagulase negative
staphylococci(MRCNS), enterococcus and penicillin resistant
streptococcus pneumoniae(PRSP).
8.Nitroimidazoles: Metronidazole, tinidazole, ornidazole

strong antimicrobial activity against anaerobic bacteria,

trichomonad, amoeba and giardia lamblia
Treatment of mixed infections caused various anaerobic bacteria,
including abdominal infection, pelvic infection, lung abscess
and brain abscess.
9. Antifungals: Amphotericin B, fluconazole, voriconazole

Amphotericin B:
invasive fungal infections
high toxicity
all kinds of adverse drug reactions
Select proper drug according to
physiological status, pathologic condition and
immune state of the patient

Patients with mild infections can take oral antibiotics.

Patients with severe infections or poor immunity should use
strong bactericidal effect after a correct evaluation.
Liver is a metabolic organ for most drugs
Table 3 Antimicrobial application in patients with hypohepatia

application antimicrobial agents

penicillin, cefazolin, ceftazidime, gentamicin,
Normal dosage tobramycin, amikacin, vancomycin, norvancomycin,
polymyxin, ofloxacin, ciprofloxacin, norfloxacin

piperacillin, azlocillin, mezlocillin, cephalothin,

reduce the dosage due to severe
cefotaxime, ceftriaxone, cefoperazone, erythromycin,
liver disease
clindamycin, metronidazole, fluorouracil, itraconazole

reduce the dosage lincomycin, pefloxacin, isoniazid

tetracyclines, chloramphenicol, rifampicin,

avoid using amphotericin B, ketoconazole, terbinafine,
sulfanilamide
 Kidney: Drug excretion is one important function
Table 4 Antimicrobial application in patients with
kidney function decrease
application antimicrobial agents
macrolides, rifampicin, clindamycin, doxycycline, ampicillin,
amoxicillin, piperacillin, mezlocillin, benzoxicillin, cefoperazone,
ceftriaxone, cefotaxime, cefoperazone sulbactam, ampicillin
normal dosage, or reduce slightly
sulbactam, amoxicillin clavulinic acid, piperacillin-tazobactam,
chloramphenicol, amphotericin B, isoniazid, metronidazole,
itraconazole oral solution

penicillin, carboxylbenzicillin, aloxicillin, cefazolin, cefalotin,

cephalexin, cephradine, cefuroxime, cefoxitin, ceftazidime,
ceftizoxime, cefepime, aztreonam, imipenem and cilastatin,
reduce the dosage
meropenem, ofloxacin, ciprofloxacin, sulfamethoxazole,
trimethoprim, fluconazole, pyrazinamide, vancomycin,
norvancomycin, teicoplanin

avoid using, or adjust dosage regimen when gentamicin, tobramycin, amikacin, streptomycin, itraconazole,
the indication is clear voriconazole injection
avoid using tetracycline, nitrofurantoin, terbinafine
 Table 5 Antimicrobial safety classification in pregnant women
FDA classification
A.no dangerous
B.no dangerous in animal research, but not
sure for humans
C.toxicity in animal research,data of
human research is not sufficient, and the
benefit may be more than the risk
D.Dangerous to humans, avoid using
E.teratogenesis, forbidden
antimicrobial agents
none
penicillins, cephalosporins, β- lactamase inhibitors,
aztreonam, meropenem, ertapenem, erythrocin,
azithromycin, clindamycin, amphotericin B, terbinafine,
rifabutin, ethambutol, metronidazole, macrodantin
imipenem and cilastatin, chloramphenicol, clarithromycin,
vancomycin, fluconazole, itraconazole, ketoconazole,
flucytosine, fluoroquinolones, linezolid, pyrimethamine,
rifampicin, isoniazid, pyrazinamide
aminoglycosides, tetracyclines
quinine, ethionamide, ribavirin
Preventive application of antibacterial agents

1. Non-surgical patients(refer to “③cases that should not use

antimicrobial agents”)
2. Perioperative period of surgery

In principle, no antibacterial agents during perioperative period of

clean surgery.

Drug was used within 0.5-1 hour before surgery, or at the beginning
of anesthesia. If the surgery lasts more than 3 hours or the blood
loss is big(>1500 ml), drug can be used during the surgery once
more. The total time should not more than 24 hours, and no more
than 48 hours in individual case.
Table 6 Antimicrobial agent selection in Perioperative period of surgery
 surgery antimicrobial agents
the first and second generation of cephalosporins
craniocerebral operation vancomycin in MRSA high-risk units

neck operation the first and second generation of cephalosporins

the first and second generation of cephalosporins, adding metronidazole
surgery through the oropharyngeal mucosa incision
properly
breast surgery the first and second generation of cephalosporins
vascular surgery the first and second generation of cephalosporins
surgery for external abdominal hernia the first and second generation of cephalosporins
gastroduodenal surgery the first and second generation of cephalosporins
the first and second generation of cephalosporins or cefotaxime, adding
appendix operation metronidazole properly
cephamycin singly
the first and second generation of cephalosporins or ceftriaxone, adding
colorectal surgery metronidazole properly
cephamycin singly
the first and second generation of cephalosporins or ceftriaxone, adding
hepatobiliary operation metronidazole properly
cephamycin singly
thoracic surgery the first and second generation of cephalosporins
the first and second generation of cephalosporins
cardio vascular surgery vancomycin in MRSA high-risk units

urinary surgery the first and second generation of cephalosporins, quinolones

general orthopedic surgery the first and second generation of cephalosporins
the first and second generation of cephalosporins
orthopedic surgery used artificial implants vancomycin in MRSA high-risk units

the first and second generation of cephalosporins, adding metronidazole

gynecological operation
properly
cesarean section the first and second generation of cephalosporins
Clinical application strategy

1. De-escalating therapy: broad-spectrum antibiotic agent or

drug combination at the beginning, sensitive or narrow-
spectrum antibiotic agent after getting the pathogen

2. Short course of treatment

3. drug combination

4. Reduce applying antimicrobial drugs that have bacterial

resistance
Table 7 Antimicrobial agents application against common resistant
bacteria in clinic

drug-resistant bacteria priority drug alternative drug

methicillin-resistant Staphylococcus
vancomycin, norvancomycin linezolid, teicoplanin, daptomycin
aureus

penicillin not sensitive to streptococcus levofloxacin, moxifloxacin, vancomycin,

pneumoniae norvancomycin

enterobacteriaceae produced extended- piperacillin and tazobactam, latamoxef,

ertapenem
spectrum beta-lactamase cefmetazole

enterobacteriaceae produced
cefepime ertapenem
cephalosporin enzyme

carbapenem - resistant
bacillosporin, tigecycline
enterobacteriaceae

carbapenem - resistant acinetobacter

bacillosporin, tigecycline, sulbactam
baumannii

carbapenem - resistant pseudomonas

bacillosporin
aeruginosa