254 CHAPTER 11 Anti-Infectives

Síntese da parede Replicação de ADN (AND-

Celular girase)
Cicloserina
Acido Nalidixico
Vancomicina Flúorquinolonas AND-dependente Polimerase de
Bacitracina ARN
Fosfomicina Rifampin
Penicillinas
Cefalosporinas
Manobactams DNA
Carbapenems
THF A Síntese Proteica
mRNA (50S inibidor)
Metabolismo do
acido fólico Ribossoma Eritromicina
DHF A
Cloranfenicol
Trimetroprim 50 50 50 Clindamicina
Sulfonamidas 30 30 30

Síntese proteica
PABA (30S Inibidor )
Terraciclina

Membrana Celular
Polimixinas Estreptomicina
Gentamicina,

Figura 1. Antimicrobianos: Mecanismo de ação

PABA- Ácido p-aminobenzoico, DHF A – Ácido dihidrofólico, THF A – Ácido tetrahidrofólico

Resistance to Penicillins became available for the treatment of many gram-positive

Bacterial resistance to penicillin exists secondary to several
different bacterial characteristics and/or mechanisms.
First, the penicillins poorly penetrate into the intracellular
space and are therefore ineffective against obligate intracel-
lular organisms such as Rickettsia or Chlamydia. Nor are
they effective against gram-negative bacteria because the
peptidoglycan wall is not exposed to the antibiotic in gram-
negative bacteria. Some gram-negative bacteria also have
pores in the outer membrane that do not allow passage of
beta-lactam antibiotics. Other bacteria have efflux pumps
that remove the antibiotic from the periplasmic space.
Some bacteria, such as Mycoplasma, do not make pepti-
doglycan and are therefore impervious to the mechanism
of action of beta-lactam antibiotics. Bacteria that do have
peptidoglycan can alter the form of peptidoglycan made so
the beta-lactam antibiotics are ineffective. Finally, bacterial
development of enzymes beta-lactamase or penicillinase
is a common mechanism of resistance. lhese enzymes
break open the beta-lactam ring of the penicillin molecule
and render it inactive.16
Natural Penicillins
In the late 1920s, natural penicillins were identified, and
by 1950, penicillin G was proven to be bactericidal and
and gram-negative cocci, anaerobes, and spirochetes.
Table 11-2 lists the indications, doses, and adverse reac-
tions to the most commonly used penicillins. lhe two nat-
ural penicillins used today are benzylpenicillin, also known
as penicillin G, which can only be given intravenously, and
penicillin V, which is the oral formulation. Procaine peni-
cillin (Bicillin CR) is penicillin G in combination with a
local anesthetic (procaine), making it useful for intramus-
cular injection. Benzathine benzyl penicillin (Bicillin LA) is
a form of penicillin G that is slowly absorbed then hydro-
lyzed to penicillin G internally. It is used when prolonged
concentrations are required. It is important not to confuse
Bicillin CR and Bicillin LA. Bicillin CR has 1.2 million units
of penicillin G and 1.2 million units of procaine. Bicillin LA
has 2.4 million units of penicillin G.17
Penicillin G remains indicated for infections caused
by streptococci, meningococci, enterococci, penicillin-
susceptible pneumococci, and non–beta-lactamase-
producing staphylococci. lhis agent also is highly effective
against spirochetes such as Treponema pallidum, Clostrid-
ium species, actinomyces, and other gram-positive rods, but
it is inactive against most strains of Staphylococcus aureus.
Penicillin V (Veetids), also known as penicillin VK, is
similar to penicillin G, except it is acid stabile, and penicillin
G is not. Because of its acid stability, penicillin V is the drug