Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 8 ANTIBACTERIAL DRUGS
interaction has only been well documented with
cefaloridine (no longer marketed).
● Furosemide could theoretically increase the nephrotoxic
potential of cephalosporins but this has not
been reported clinically.
● Some parenteral cephalosporins such as ceftazidime
may cause pain when administered IM or SC. Sterile
abscesses or other local tissue reactions may occur
but are uncommon. Thrombophlebitis may occur
after IV administration.
● Except for cefotaxime, cephalosporins may cause
false-positive urine glucose determinations when
using cupric sulfate solution (Benedict’s solution,
Clinitest ® ). Tests using glucose oxidase (Tes-Tape ® ,
Clinistix ® ) are not affected.
● When using Jaffe’s reaction to measure blood or
urine creatinine, cephalosporins other than cefotaxime
and ceftazidime in high doses may cause falsely
increased values.
● On rare occasions, ceftazidime causes false-positive
Coombs’ tests and increases prothrombin times.
CARBAPENEMS
Imipenem
Antibacterial spectrum (Fig. 8.12)
Imipenem is a β-lactam antibacterial classified as a carbapenem
that has the widest activity of all individual
antibacterial drugs. It is active against almost all clinically
important aerobic and anaerobic Gram-positive or
Gram-negative cocci and rods. Nocardia and Brucella
are susceptible. MRSA is resistant.
Resistance
Resistance during therapy has been commonly reported
in Pseudomonas aeruginosa and attributed to reduced
membrane permeability due to alterations in outer
membrane proteins.
Clinical applications
Imipenem is used in human medicine to treat hospitalacquired
infections caused by multiple-resistant Gramnegative
bacteria, or mixed aerobic and anaerobic
infections, including those in immunocompromised
hosts. Veterinary use is rarely warranted but could be
considered for serious and multiresistant bacterial infections
when single-agent treatment is sought or when less
expensive antibiotics are ineffective or pose unacceptable
risks.
Pharmacokinetics
Imipenem is available as a fixed-dose combination with
cilastatin. Imipenem is not absorbed after administration
PO. Following IV administration it is widely distributed
to extracellular fluid and reaches therapeutic
concentrations in most sites in humans, including the
CSF in meningitis. Bioavailability after IM administration
in humans is about 95% for imipenem and 75%
for cilastatin. In dogs bioavailability of imipenem after
SC administration is complete. Imipenem crosses the
placenta and passes into milk.
Imipenem is almost exclusively eliminated renally,
after being metabolized in renal tubules by a dipeptidase.
Cilastatin prevents this process so that active drug is
excreted into the urine in large amounts. Cilastatin does
not affect systemic pharmacokinetic behavior but may
protect against proximal tubular necrosis, which can
occur when imipenem is used alone. Half-life in patients
with normal renal function is 1–3 h on average.
Adverse effects
● The most common adverse effects in humans are
gastrointestinal disturbances and cutaneous hypersensitivity
reactions.
● Seizures and tremors have occurred in a small percentage
of patients, associated with high doses, renal
failure or underlying neurological abnormality.
● Infusion reactions such as thrombophlebitis or gastrointestinal
toxicity after rapid infusion have been
reported.
Gram positive
aerobes
Obligate
anaerobes
* MRSA are resistant
Gram negative
aerobes
Penicillinaseproducing
Staphylococcus*
Fig. 8.12 Antibacterial spectrum for imipenem.
Known drug interactions
● Additive or synergistic antibacterial effects may
occur against some bacteria when imipenem is used
with an aminoglycoside.
● Antagonism of antibacterial effects may occur if used
with other β-lactam antibacterials.
● Synergy may occur against Nocardia asteroides
when used in combination with trimethoprimsulfonamide.
● Chloramphenicol may antagonize the antibacterial
efficacy of imipenem.
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