Penicillinase-resistant penicillins
Most staphylococci are now resistant to benzylpenicillin
sodium because they produce penicillinases. Flucloxacillin
p. 345 , however, is not inactivated by these enzymes and is
thus effective in infections caused by penicillin-resistant
staphylococci, which is the main indication for its use.
Flucloxacillin is acid-stable and can, therefore, be given by
mouth as well as by injection. Flucloxacillin is well absorbed
from the gut.
Broad-spectrum penicillins
Ampicillin p. 341 is active against certain Gram-positive and
Gram-negative organisms but is inactivated by penicillinases
including those produced byStaphylococcus aureusand by
common Gram-negative bacilli such asEscherichia coli.
Ampicillin is also active againstListeriaspp. and enterococci.
Almost all staphylococci, approx. 60 %ofE. colistrains and
approx. 20 %ofHaemophilus influenzaestrains are now
resistant. The likelihood of resistance should therefore be
considered before using ampicillin for the‘blind’treatment
of infections; in particular, it should not be used for hospital
patients without checking sensitivity.
Ampicillin can be given by mouth, but less than half the
dose is absorbed and absorption is further decreased by the
presence of food in the gut. Ampicillin is well excreted in the
bile and urine.
Amoxicillin p. 339 is a derivative of ampicillin and has a
similar antibacterial spectrum. It is better absorbed than
ampicillin when given by mouth, producing higher plasma
and tissue concentrations; unlike ampicillin, absorption is
not affected by the presence of food in the stomach.
Amoxicillin or ampicillin are principally indicated for the
treatment of community-acquired pneumonia and middle
ear infections, both of which may be due toStreptococcus
pneumoniaeandH. influenzae, and for urinary-tract
infections. They are also used in the treatment of
endocarditis and listerial meningitis. Amoxicillin may also
be used for the treatment of Lyme disease [not licensed].
Maculopapular rashes occur commonly with ampicillin
(and amoxicillin) but are not usually related to true penicillin
allergy. They often occur in children with glandular fever;
broad-spectrum penicillins should not therefore be used for
‘blind’treatment of a sore throat. The risk of rash is also
increased in children with acute or chronic lymphocytic
leukaemia or in cytomegalovirus infection.
Co-amoxiclav p. 343 consists of amoxicillin with the beta-
lactamase inhibitor clavulanic acid. Clavulanic acid itself has
no significant antibacterial activity but, by inactivating beta-
lactamases, it makes the combination active against beta-
lactamase-producing bacteria that are resistant to
amoxicillin. These include resistant strains ofStaph. aureus,
E. coli, andH. influenzae, as well as manyBacteroidesand
Klebsiellaspp. Co-amoxiclav should be reserved for
infections likely, or known, to be caused by amoxicillin-
resistant beta-lactamase-producing strains.
A combination of ampicillin withflucloxacillin (as co-
fluampicil p. 342 ) is available to treat infections involving
either streptococci or staphylococci (e.g. cellulitis).
Antipseudomonal penicillins
Piperacillin, a ureidopenicillin, is only available in
combination with the beta-lactamase inhibitor tazobactam.
Ticarcillin, a carboxypenicillin, is only available in
combination with the beta-lactamase inhibitor clavulanic
acid. Both preparations have a broad spectrum of activity
against a range of Gram-positive and Gram-negative
bacteria, and anaerobes. Piperacillin with tazobactam p. 337
has activity against a wider range of Gram-negative
organisms than ticarcillin with clavulanic acid p. 337 and it is
more active againstPseudomonas aeruginosa. These
antibacterials are not active against MRSA. They are used in
the treatment of septicaemia, hospital-acquired pneumonia,
and complicated infections involving the urinary-tract, skin
and soft tissue, or intra-abdomen. They may be used for the
empirical treatment of septicaemia in immunocompromised
children but otherwise should generally be reserved for
serious infections resistant to other antibacterials. For
severe pseudomonas infections these antipseudomonal
penicillins can be given with an aminoglycoside (e.g.
gentamicin) since they have a synergistic effect.
Piperacillin with tazobactam is used in cysticfibrosis for
the treatment ofPs. aeruginosacolonisation when
ciprofloxacin p. 348 and nebulised colistimethate sodium
p. 346 have been ineffective; it can also be used in infective
exacerbations, when it is combined with an aminoglycoside.
Mecillinams
Pivmecillinam hydrochloride p. 344 has significant activity
against many Gram-negative bacteria includingEscherichia
coli, klebsiella, enterobacter, and salmonellae. It is not active
againstPseudomonas aeruginosaor enterococci.
Pivmecillinam hydrochloride is hydrolysed to mecillinam,
which is the active drug.
Penicillins f
lDRUG ACTIONThe penicillins are bactericidal and act by
interfering with bacterial cell wall synthesis. They diffuse
well into body tissues andfluids, but penetration into the
cerebrospinalfluid is poor except when the meninges are
inflamed. They are excreted in the urine in therapeutic
concentrations.
lCAUTIONSHistory of allergy
lSIDE-EFFECTS
▶Common or very commonDiarrhoea.hypersensitivity.
nausea.skin reactions.thrombocytopenia.vomiting
▶UncommonAntibiotic associated colitis.leucopenia
▶Rare or very rareAgranulocytosis.angioedema.
haemolytic anaemia.hepatic disorders.nephritis
tubulointerstitial.neutropenia.seizure.severe cutaneous
adverse reactions (SCARs)
SIDE-EFFECTS, FURTHER INFORMATIONDiarrhoea
frequently occurs during oral penicillin therapy. It is most
common with broad-spectrum penicillins, which can cause
antibiotic-associated colitis.
lALLERGY AND CROSS-SENSITIVITYThe most important
side-effect of the penicillins is hypersensitivity which
causes rashes and anaphylaxis and can be fatal. Allergic
reactions to penicillins occur in 1 – 10 % of exposed
individuals; anaphylactic reactions occur in fewer than
0. 05 % of treated patients. Patients with a history of atopic
allergy (e.g. asthma, eczema, hay fever) are at a higher risk
of anaphylactic reactions to penicillins. Individuals with a
history of anaphylaxis, urticaria, or rash immediately after
penicillin administration are at risk of immediate
hypersensitivity to a penicillin; these individuals should
not receive a penicillin. Individuals with a history of a
minor rash (i.e. non-confluent, non-pruritic rash restricted
to a small area of the body) or a rash that occurs more than
72 hours after penicillin administration are probably not
allergic to penicillin and in these individuals a penicillin
should not be withheld unnecessarily for serious
infections; the possibility of an allergic reaction should,
however, be borne in mind. Other beta-lactam antibiotics
(including cephalosporins) can be used in these patients.
Patients who are allergic to one penicillin will be allergic
to all because the hypersensitivity is related to the basic
penicillin structure. Patients with a history of immediate
hypersensitivity to penicillins may also react to the
cephalosporins and other beta-lactam antibiotics, they
should not receive these antibiotics. If a penicillin (or
another beta-lactam antibiotic) is essential in an
individual with immediate hypersensitivity to penicillin
336 Bacterial infection BNFC 2018 – 2019
Infection
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