Antibiotics I Margaret K. Hostetter, M.D.
Has the Antibiotic Era Ended? Number of New Antibiotics Clinical Infectious Diseases, May 1, 2004
Principles of Antibiotic Treatment Three qualities of the desirable antibiotic: • ABSORPTION in concentrations sufficient to kill the organism • PENETRATION to the site of infection • BACTERICIDAL CAPACITY
Principles of Antibiotic Treatment • EMPIRIC choice at the outset (“wide net”) • List the likely causes and the antibiotics to which they are susceptible • Cover the most likely causes • Avoid duplication of coverage
Principles of Antibiotic Treatment • THERAPEUTIC choice when the causative organism is identified • Cover the narrowest possible spectrum • Address allergies • Explain possible side effects
Enterobacter Grp B strep Grp A strep Klebsiella St. aureus Pseud spp Serratia Pneum Ps.aerug St. epi B. fragilis Listeria H. flu E. coli Mouth Gut GRAM POSITIVESGRAM NEGATIVESANAEROBES Meningococcus Enterococcus
Structure of b-Lactams R group R group R-Groups helios.bto.ed.ac.uk/bto/microbes/penicill.htm
Natural + Penicillins Anti-Staph + Penicillins +Aminopenicillin Ureidopenicillins (Piperacillin) Carboxypenicillins (Ticarcillin) + + GRAM POSITIVESGRAM NEGATIVESANAEROBES Enterococcus Meningococcus Enterobacter Grp B strep Grp A strep Klebsiella St. aureus Pseud spp Serratia Pneum Ps.aerug St. epi B. fragilis Listeria H. flu E. coli Mouth Gut +- requires addition of aminoglycoside
ANTI-STAPH PENICILLINS EXTENDED-SPECTRUM PENICILLINS ANY PENICILLIN HEMATOLOGIC Coombs-positive hemolytic anemia Neutropenia Thrombocytopenia RENAL Interstitial nephritis Hemorrhagic cystitis SUPERINFECTION with RESISTANT flora NEUROLOGIC Seizures with renal compromise HEPATIC Hepatitis GRAM POSITIVESGRAM NEGATIVESANAEROBES Enterococcus Meningococcus Enterobacter Grp B strep Grp A strep Klebsiella St. aureus Pseud spp Serratia Pneum Ps.aerug St. epi B. fragilis Listeria H. flu E. coli Mouth Gut SIDE EFFECTS of the PENICILLINS Mayo Clin Proc 1991; 66:1047-1063 Goodman&Gilman, 20th ed., Ch. 45
Case Study A 10-year-old boy is admitted for osteomyelitis of the calcaneus due to Pseudomonas aeruginosa, confirmed by culture. His temperature is 103oC, and his WBC is 18,000 with 80% neutrophils and 20% lymphs. He is begun on Ticarcillin 300 mg/kg/day and Tobramycin 4.5 mg/kg/day. He defervesces within 4 days, and his WBC count falls to 10,000 with 50% neutrophils and 50% lymphs. You are asked to consult on day 10 because of a return of fever. His laboratory values are as follows: DATE TEMP WBC %N %L 6/11 103 18,000 80 20 6/15 98 10,000 50 50 6/19 100 4,000 50 50 6/21 101 2,000 20 80
Question What should you do if an immunologically normal patient on Ticarcillin and Gentamicin for an uncomplicated Pseudomonas aeruginosa infection develops neutropenia?
Case Study A 6-year-old boy with a group A streptococcal pneumonia and empyema has no history of penicillin allergy. His organism is sensitive to penicillin, and IV therapy is begun with 200,000 u/kg/day of aqueous penicillin G. Within 30 minutes he develops urticaria over his trunk and upper extremities. What do you do? What if he develops urticaria within 2 hours? What if he develops a morbilliform rash within 4 days?
Case Study A 15-year-old boy is seen in the urgent care clinic with complaint of sore throat and fever to 102oC. On exam, he has a beefy red pharynx, bilateral exudative tonsillitis, and marked cervical adenopathy. A rapid strep test is negative, but he is sent home on Amoxicillin to await the results of the throat culture. His mother calls the next morning to report an erythematous maculopapular rash covering his entire body.
Case Study A 6-month-old female suffers a prolonged hypoxic episode while undergoing surgery for tetralogy of Fallot. Within 24 hours she is oliguric, and her blood cultures are positive for Enterococcus faecalis, sensitive to penicillin and aminoglycosides. She is begun on Ampicillin at 200 mg/kg/day divided q6 hours and is given one dose of Gentamicin at 1.5 mg/kg because her creatinine is 2.5. Twenty-four hours into therapy, she suffers a grand mal seizure.
GRAM POSITIVESGRAM NEGATIVESANAEROBES Enterococcus Meningococcus Enterobacter Grp B strep Grp A strep Klebsiella St. aureus Pseud spp Serratia Pneum Ps.aerug St. epi B. fragilis Listeria H. flu E. coli Mouth Gut PARENTERAL CEPHALOSPORINS 1st Generation 2nd Generation 3rd Generation 4th Generation Anaerobic Cefotaxime Cefipime Cephalothin=Keflin Cefuroxime Cefoxitin Ceftriaxone Cephazolin=Kefzol Cefotetan Ceftazidime ORAL CEPHALOSPORINS Cephalexin (Keflex) Cefuroxime axetil Cefpodoxime (Vantin) Cefaclor Cefprozime (Cefzil) Cephadroxil (Duricef) Cefixime (Suprax) Cefdinir (Omnicef) Owen MJ. Am J Dis Child 1993; 147:81-6.
1st Gen Cefotetan 2nd Generation 3rd Generation -Cefotaxime Ceftriaxone 3rd Generation - Ceftazidime GRAM POSITIVESGRAM NEGATIVESANAEROBES Enterococcus Meningococcus Enterobacter Grp B strep Grp A strep Klebsiella St. aureus Pseud spp Serratia Pneum Ps.aerug St. epi B. fragilis Listeria H. flu E. coli Mouth Gut XXX Mayo Clin Proc 1991; 66:1064-1073.
1st or 2nd GENERATION 3rd GENERATION ANY CEPHALOSPORIN HEMATOLOGIC Positive Coombs test, but clin. insignificant anemia Neutropenia Thrombocytopenia Bleeding disorders with MTT - treat with vitamin K Impaired platelet aggregation METABOLIC False-+ Clinitest for glucosuria Artifactual increase in creatinine SUPERINFECTION with RESISTANT flora GALL BLADDER SLUDGE with Ceftriaxone IMMUNOLOGIC Serum sickness with Ceclor (PO) GRAM POSITIVESGRAM NEGATIVESANAEROBES Enterococcus Meningococcus Enterobacter Grp B strep Grp A strep Klebsiella St. aureus Pseud spp Serratia Pneum Ps.aerug St. epi B. fragilis Listeria H. flu E. coli Mouth Gut SIDE EFFECTS of the CEPHALOSPORINS Mayo Clin. Proceedings 66:1q064-1073, 1991
Case Study A 2-year-old unvaccinated little boy is admitted with fever of 3 days’ duration and refusal to walk on the right leg. Ultrasound of the right hip shows a large effusion and displacement of the femoral head. a. differential diagnosis? b. causative organisms? c. antibiotic regimen?
Case Study A 6-year old female is transferred from an outlying hospital with a positive blood culture for Streptococcus pyogenes and an effusion of the left hip. When she returns to the floor from an open drainage procedure in the OR, you inform the mother that you plan to begin _____________. What do you do when the mother says, a. “She’s had lots of penicillin before and never had a rash until last month, when she got oral Ampicillin for a sore throat and on the third day broke out in a rash that covered her whole body.” b. “She always gets a prickly heat type of rash to any drug that ends in ‘cillin’.” c. “She’s only had a penicillin shot once before and got hives right away and then had trouble breathing.”
Case Study A 2-year-old boy who has received only one Hib vaccine has developed septic arthritis and osteomyelitis of the left hip and femur secondary to Haemophilus influenzae type b. During his third week of therapy with Ceftriaxone, 75 mg/kg QD, he begins to complain of right upper quadrant pain. On physical exam, he is anicteric, but a 3x3 cm mass is felt in the right upper quadrant. What do you do now?
Case Study A 16-month-old girl with a history of recurrent otitis media presents with purulent drainage from the left ear. A culture grows Streptococcus pneumoniae, sensitive to penicillin. Her mother tells you that she developed a maculopapular rash after a week of Amoxicillin therapy for her last otitis. Your best choice is: a. Amoxicillin b. Amoxicillin-clavulanate c. Cefuroxime-axetil (Ceftin) d. Suprax e. Ciprofloxacin
Case Study A 12-year-old girl presents to the ED during her second week of induction chemotherapy for ALL. She is febrile to 103˚, hypotensive, and hypoxic. Her physical exam shows no focal findings. She has a new central venous catheter in place. Her WBC count is 800 with 0% neutrophils.
Case Study A 16-year-old boy who is neutropenic after induction chemotherapy for ALL presents with a painful, enlarging black lesion on his thigh and a fever to 103o. Gram stain shows gram negative bacilli. Your clinical diagnosis and choice of therapy are: a. Haemophilus influenzae: Cefotaxime b. Pseudomonas aeruginosa: Ceftazidime c. Pseudomonas aeruginosa: Ceftazidime and Tobramycin d. Bacteroides fragilis: Cefoxitin Pizzo P et al. NEJM 1986; 315:552-8.EORTC. JID 1978; 137:14-28.