Monobactams

Full Urticaria Cure

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Another interesting group of compounds produced by several bacterial genera are the monocyclic p-lactams (monobactams). The natural monobactams have little antimicrobial activity. A synthetic derivative, aztreonam (Azactam), has excellent activity against gram-negative organisms, including P. aeruginosa. Aztreonam has low affinity for penicillin-binding proteins in streptococci, staphylococci, and anaerobes and therefore has no significant activity against gram-positive bacteria or anaerobes. Specific activity against gram-negative organisms relates to the aminothiazolyl oxime moiety on the acyl side chain. Addition of two methyl groups and a car-boxylic acid group on the oxime side chain enhances activity against P. aeruginosa.Aztreonam is stable to most p-lactamases (chromosomal and plasmid).

The pharmacokinetic properties of aztreonam are similar to those of the parenteral cephalosporins (Table 45.2). Aztreonam is not bioavailable after oral administration. During its distribution phase, the drug can achieve therapeutic concentrations in cerebrospinal fluid in the presence of inflamed meninges. Consequently, aztreonam is an alternative antibiotic to the cephalosporins for the therapy of meningitis caused by gram-negative bacilli.

Aztreonam may be used as a substitute for an aminoglycoside in the treatment of infections caused by susceptible gram-negative organisms. Most of the adverse effects of aztreonam are local reactions at the site of injection. Interestingly, aztreonam rarely causes allergic reactions in patients with a history of type I hypersensitivity to other p-lactam antibiotics.

^Study Questions

1. A 32-year-old man with quadriplegia and neuro-genic bladder was admitted to the hospital from a long-term care facility. The patient had vomiting, fever, and cloudy urine. A year ago, the patient developed urticaria, wheezing, and hypotension within an hour after his first dose of nafcillin. Subsequently his penicillin skin test was positive. During the current admission, the physician examiner noted fever, quadriplegia, and chronic indwelling bladder catheter. Laboratory tests revealed leukocytosis in blood and urine. Urine stain showed gram-negative rods, and urine culture grew P. aeruginosa. Which of the following drugs would be most appropriate for this patient?

(A) Ampicillin-sulbactam

(B) Aztreonam

(C) Cefazolin

(D) Imipenem-cilastatin

(E) Piperacillin-tazobactam

2. A 22-year-old woman had her first prenatal visit. Her physical examination was normal for a woman at 12 weeks' gestation. Both the nontreponemal (Venereal Disease Research Laboratory) and fluorescent treponemal antibody tests were positive. She denied previous treatment for syphilis. She could not recall signs or symptoms of primary or secondary syphilis in the past year. She had no previous syphilis serology tests for purposes of comparison. Which of the following would be the best treatment for the patient?

(A) Benzathine penicillin G

(B) Doxycycline

(C) Spectinomycin

(D) Streptomycin

(E) Tetracycline

3. A 26-year-old woman, a kindergarten teacher, had pharyngitis last year treated with ampicillin for 3 days. She stopped the ampicillin when she learned her throat culture was negative. Three days after she stopped the ampicillin, she developed a rash. Her physician noted symmetrical erythematous confluent macular-papular eruptions on her extremities with no urticaria. The physician diagnosed non-IgE-mediated ampicillin eruption. Now the patient returns with new fever and sore throat. She has no cough or rash. Her physical examination is normal except for fever, tender anterior cervical lymphadenopathy, and tonsillar exudate. Her rapid streptococcal test of a pharyngeal specimen is positive. Which of the following would be the most appropriate treatment for this patient?

(A) Amikacin

(B) Lomefloxacin

(C) Metronidazole

(D) Netilmicin

(E) Penicillin V

4. A 24-year-old man came to the public health clinic because of a urethral discharge. He had had unprotected intercourse with multiple partners. Physical examination revealed a purulent urethral discharge with no penile ulcers or vesicles. There was no inguinal adenopathy. Gram stain of the discharge revealed gram-negative diplococci inside leukocytes. The antibiotic used to treat the patient's infection has which of the following mechanisms of action?

(A) Inhibits cell membrane integrity by binding to ergosterols to create pores

(B) Inhibits dihydrofolate reductase, thereby blocking formation of tetrahydrofolate required for purine synthesis

(C) Inhibits KasA, a p-ketoacyl carrier protein syn-thetase, thereby blocking mycolic acid synthesis

(D) Inhibits RNA synthesis by binding to the p-subunit of DNA-dependent RNA polymerase

(E) Inhibits transpeptidase, thereby blocking cross-linking of peptides in cell wall murein (peptidogly-can)

5. Parents brought their 3-year-old boy to the outpatient clinic because of a facial rash. Today the patient was one of several children sent home from day care because of similar rashes. Physical examination revealed a normal, healthy boy with discrete erythe-matous papular eruptions on his cheeks. There were no vesicles or bullae. The rash was covered with a honey crust, suggesting impetigo. Which of the following treatments would be most appropriate?

(A) Dapsone

(B) Dicloxacillin

(C) Doxycycline

(D) Ketoconazole

(E) Penciclovir

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