Clinical Use of Antimicrobial
Agents
The
development of antimicrobial drugs represents one of the most important
advances in therapeutics, both in the control or cure of serious infections and
in the prevention and treatment of infectious complications of other
therapeutic modalities such as cancer chemotherapy, immunosuppression, and
surgery. However, evidence is overwhelming that antimicrobial agents are vastly
overprescribed in outpatient settings in the United States, and the
availability of antimicrobial agents without prescription in many developing
countries has—by facilitating the development of resistance—already severely
limited therapeutic options in the treatment of life-threatening infections.
Therefore, the clinician should first determine whether antimicrobial therapy
is warranted for a given patient. The specific questions one should ask include
the following:
1. Is an antimicrobial
agent indicated on the basis of clinical findings? Or is it prudent to wait
until such clinical findings become apparent?
2. Have appropriate
clinical specimens been obtained to establish a microbiologic diagnosis?
3. What are the likely etiologic agents for the
patient’s illness?
4. What measures
should be taken to protect individuals exposed to the index case to prevent
secondary cases, and what mea-sures should be implemented to prevent further
exposure?
5.
Is there clinical evidence (eg, from well-executed clinical trials) that antimicrobial
therapy will confer clinical benefit for the patient?
Once a specific cause
is identified based on specific microbio-logic tests, the following further questions
should be considered:
1.
If a specific microbial pathogen is identified, can a narrower-spectrum agent
be substituted for the initial empiric drug?
2. Is one agent or a combination of agents
necessary?
3. What are the
optimal dose, route of administration, and dura-tion of therapy?
4. What specific tests
(eg, susceptibility testing) should be under-taken to identify patients who
will not respond to treatment?
5. What adjunctive
measures can be undertaken to eradicate the infection? For example, is surgery
feasible for removal of devi-talized tissue or foreign bodies—or drainage of an
abscess— into which antimicrobial agents may be unable to penetrate?
Is
it possible to decrease the dosage of immunosuppressive therapy in patients who
have undergone organ transplanta-tion? Is it possible to reduce morbidity or
mortality due to the infection by reducing host immunologic response to the
infec-tion (eg, by the use of corticosteroids for the treatment of severe Pneumocystis jiroveci pneumonia or
meningitis due to Streptococcus
pneumoniae)?
CASE STUDY
A 51-year-old alcoholic patient presents to the emergency department with fever, headache, neck stiffness, and altered mental status for 12 hours. Vital signs are blood pressure 90/55 mm Hg, pulse 120/min, respirations 30/min, tempera-ture 40°C [104°F] rectal. The patient is minimally responsive to voice and does not follow commands. Examination is sig-nificant for a right third cranial nerve palsy and nuchal rigid-ity. Laboratory results show a white blood cell count of 24,000/mm3 with left shift, but other hematologic and chem-istry values are within normal limits. An emergency CT scanof the head is normal. Blood cultures are obtained, and a lumbar puncture reveals the following cerebrospinal fluid (CSF) values: white blood cells 5000/mm 3, red blood cells 10/mm3, protein 200 mg/dL, glucose 15 mg/dL (serum glucose 96 taken at same time). CSF Gram stain reveals gram-positive cocci in pairs. What is the most likely diagnosis in this patient? What organisms should be treated empirically? Are there other pharmacologic interventions to consider before initiating antimicrobial therapy?
CASE STUDY ANSWER
The most likely diagnosis for this patient is Streptococcuspneumoniae meningitis, the most common bacterial cause of meningitis in adults. Other possible microbiologic etiologies include Neisseria meningitidis, Listeria monocytogenes, and enteric gram-negative bacilli. Intravenous antimicrobials to which local strains of these organisms are sensitive should be started while awaiting culture and sensitivity results. In addition, the use of dexamethasone has also been demonstrated to reduce mortality in adults with pneumococcal meningitis in conjunction with appropriate antimicrobial therapy.
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