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Antibacterial Drugs

last authored: Feb 2010, David LaPierre
last reviewed:

Introduction

antibiotic sensitivity and resistance
image courtesy of CDC

There are many drugs available to treat bacterial infections, with different drug types best suited for treating specific infections.

Effective diagnosis, made with a combination of clinical and laboratory findings, helps with the decision.

Emperic therapy can also be used.

Cell Wall Inhibitors

penicillins
cephalosporins
carbapenems
glycopeptides

Penicillins bind to penicillin binding proteins (PBPs), leading to distorted cell walls and lysis.

drugs	coverage	indications	adverse effects
benzyl penicillin penicillin G (IV) penicillin V (PO)	gram-positives NOT Staph NOT Enterococcus oral anaerobes NOT Bacteroides Treponema	mild-to-moderate infections: actinomycosis, strep pharyngitis, rheumatic fever, streptococcal skin and soft tissue infections	immediate allergy: anaphylaxis, urticaria delayed allergy (IgG): urticaria, rash, serum sickness dose-related toxicity: seizures, electropyte problems, bleeding diarrhea
aminopenicillin ampicillin IV amoxicillin PO	same as penicillin Enterococcus Listeria	meningitis, endocarditis, AOM, pharyngitis, sinusitis, AE-COPD, H pylori, Lyme disease, RTI, UTI often used in combination with gentamycin (gram -ve) and clavulin (for a boost)
isoxozoyl penicillin cloxacillin methicillin nafcillin oxacillin	same as penicillin Staphylococcus
ureidopenicillin piperacillin ticeracillin	same as penicillin GNB, including Pseudomonas
lactamase inhibitors amoxicillin-clavinulate	same as penicillin Staphylococcus H. influenzae	RTI, sinusitis, AOM, skin/soft tissue infections, UTI
carboxypenicillin carbenicillin	same as penicillin extended GN coverage

Beta-lactam resistance has evolved in a number of ways. Production of beta-lactamase, altered PBP (S. pneumoniae), new PBP (MRSA), and altered permeability can all occur.

Cephalosporins bind to penicillin binding proteins (PBPs) and prevent cross-linking of peptidoglycans, leading to distorted cell walls and lysis.

drugs	coverage	indications	adverse effects
1st generation cephalexin (Keflex) PO cefazolin (Ancef)	gram-positives NOT Enterococcus gram negatives: only E coli, Klebsiella, Proteus	skin/soft tissue infections, surgery prophylaxis	15% penicillin allergy cross-reactivity nephrotoxicity
2nd generation cefuroxime (Ceftin) cefprozil (Cefzil)	weaker for GPs that 1e more coverage for GN, including anaerobes	soft tissue
3rd generation cefixime ceftriaxone	more GN than GP S aureus and streptococcus	RTI, gonorrhea, meningitis, septicemia, abdominal infections
4th generation cefepime (IV)	broad spectrum for GPs broad coverage for GNs, including Pseudomonas	emperic therapy for febrile neutropenia

Carbapenems bind to penicillin binding proteins (PBPs) and prevent cross-linking of peptidoglycans, leading to distorted cell walls and lysis.

drugs

coverage

indications

adverse effects

imipenem

gram-positives
NOT Enterococcus
NOT MRSA
gram-negatives, including Pseudomonas and Enterobacter
anaerobes

GNB with extended beta-lactamases

15% penicillin allergy cross-reactivity
seizures

meropenem

Glycopeptides bind to D-ala in nascent cell wall peptides, preventing cross-linking during peptidoglycan formation.

drugs

coverage

indications

adverse effects

vancomycin

gram-positives, including MRSA
NOT VRE
C difficile if PO

severe, life-threatening gram-positive infections

Red man syndrome (histamine, hypotension)
nephrotoxicity
ototoxicity
neutropenia, thrombocytopenia

teicoplanin

gram-positives, including MRSA
NOT most VRE

Glycopeptide resistance can be a problem in S. aureus and Enterococcus. It occurs via an altered target: D-lac in place of D-ala.

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Protein Synthesis Inhibitors

macrolides
aminoglycosides
lincosamides
tetracyclines
other

Macrolides have a broad spectrum of activity. They are bacteriostatic, with time dependent killing.

drugs	coverage	indications	adverse effects
erythromycin	GP; NOT enterococcus, MRSA GN: Legionella, B. pertussis Chlamydia Mycoplasma	RTI, pertussis, diptheria, Legionnaires disease, skin/soft tissue infections, chlamydia	nausea acute cholestatic hepatitis prolonged QT
clarithromycin (Biaxin)	same	RTI, skin infections, mycobacteria, H.pylori
azithromycin (Zithromax)	same	pharyngitis, tonsilitis, AOM, AE-COPD, community-acquired pneumonia, skin infections, campylobacter

Aminoglycosides

Aminoglycosides are excellent for gram-negatives. They are bactericidal, killing in a concentration-dependent manner.

Drugs include:

gentamycin
tobramycin
neomycin
streptomycin
amikacin

coverage

indications

adverse effects

GN, including Pseudomonas

UTI
in combination for endocarditis, neonatal pneumonia

nephrotoxicity
ototoxicity (requiring monitoring)

lincosamides

drugs

coverage

indications

adverse effects

clindamycin

GP except Enterococcus
anaerobes

suspected or proven GP, anaerobes

nausea
pseudo-membranous
colitis

Tetracyclines

tetracycline, minocycline, doxycycline

coverage	indications	adverse effects
GP anaerobes atypicals: Chlamydia, Mycoplasma, Rickettsie, Treponema malaria prophylaxis	acne Chlamydia Rickettsial infections brucellosis bartonellosis PID malaria prophylaxis	GI upset hepatotoxicity Fanconi's syndrome photosensitivity teratogenic yellow teeth and stunted growth in children

Other

chloramphenicol

coverage	indications	adverse effects
GP GN anaerobes	serious infections when suitable alternatives not available	aplastic anemia grey baby syndrome

drug	coverage	indications	adverse effects
linezolid	GP, including VRE and MRSA	VRE, MRSA as outpatient	hypertension myelosuppression, optic neuropathy, peripheral neuropathy with prolonged use

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DNA Synthesis Inhibitors

fluoroquinolones
other

Fluroquinolones

Fluoroquinolones act on DNA gyrase and topoisomerase IV. They are bactericidal, with concentration dependent killing. Bad for children, as DNA is important to them.

drugs

coverage

indications

adverse effects

ciprofloxacin
norfloxacin
ofloxacin

poor GP activity
GN: includes pseudomonas

use only when necessary to prevent resistance: RTI, UTI, prostatitis, bone and joint infections, skin and soft tissue, infectious diarrhea, intra-abdominal infections, febrile neutropenia

H/A, dizziness
allergy
seizures
prolonged QT
teratogenic
dysglycemia

levofloxacin
moxifloxacin

same as above
more GP coverage
atypicals
includes anaerobes

same as above; community-acquired pneumonia

same

Other

drug

coverage

indications

adverse effects

rifampin

GPC
N meningitidis
H. influenza
Mycobacteria

active TB, other mycobacterial infections; prosthetic endocarditis

hepatic dysfunction
inc P450
orange tears/saliva/urine

drug

coverage

indications

adverse effects

metronidazole (Flagyl)

anaerobes
Protozoa

protozoal infections (trichomonas, amebiasis, giardiasis), bacterial vaginosis, serious intra-abdominal infections

adverse effects with EtOH
seizures
peripheral neuropathy

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Metabolic Pathway Inhibitors

TMP/SMX blocks folic acid synthesis; bacteria cannot obtain folate from their environment and rely on its synthesis from PABA. Resistance if organism can bypass metabolic requirements.

drug

coverage

indications

adverse effects

trimethoprim-sulfamethoxazole (TMP/SMX)
Septra, Bactrim

GP
GN: enteric
Nocardia
Pneumocystis
Toxoplasma

UTR, RTI, GI infections, skin and soft tissue, PCP

hepatitis
Stevens-Johnson syndrome
anemia, hemolysis, leukopenia, hyperkalemia
interstitial nephritis
BM suppression

drug

coverage

indications

adverse effects

nitrofurantoin (MacroBID, Macrodantin)

enterococcus, S. saphrophyticus

lower UTI; not pyelonephritis or bactermia

cholestasis, hepatitis
hemolysis in G6PD
lung disease with chronic use

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Antimycobacterials

Always used as combination therapy (minimum three). These drugs are given over a long duration, ie 6 months or more.

drugs	coverage	indications	adverse effects
isoniazid	mycobacteria
rifampin	GPC N meningitidis H. influenza Mycobacteria	active TB, other mycobacterial infections; prosthetic endocarditis	hepatic dysfunction inc P450 orange tears/saliva/urine
ethambutol	mycobacteria
pyrazinamide	mycobacteria
sulfones	M. leprae PCP toxoplasmosis
clofazimine	M. leprae

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History of Antibiotic Development

Get JR to do a video for here...

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Resources and References

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