Case 1: Swollen arm
A 40-year-old male prisoner is hospitalized because of a three-day history of fever, hypotension and a swollen right arm. He thought that he had been bitten by a spider several days ago, although he did not see any insects on his body or elsewhere.
On physical examination, temperature is 39 °C (102.2 °F), and blood pressure is 84/64 mm Hg. The right arm is swollen and crepitant. Emergency debridement is done, and purulent material is seen. A Gram-stained specimen of this material reveals abundant gram-positive cocci in clusters. Culture results are pending.
Which of the following is the most appropriate empiric therapy at this time?
Case 2: Leg pain
A 29-year-old man comes to the emergency department because of a one-day history of increasing pain in the upper right thigh. Two days ago, he was cutting rebar (steel reinforcement used to strengthen poured concrete) with a power saw when he suddenly developed a sharp pain in his right thigh from a steel splinter thrown by the saw. The pain abated over the next hour, and there were no lesions when he examined the thigh that evening. Medical history is unremarkable.
On physical examination, temperature is 38.4 °C (101.1 °F), pulse rate is 108 beats/min, respiration rate is 16 breaths/min and blood pressure is 96/68 mm Hg. Cardiopulmonary and abdominal examinations are normal. The right thigh is moderately tender in the approximate area where the accident occurred two days earlier. There is no erythema or swelling.
Laboratory values are as follows: hemoglobin, 13.9 g/dL (139 g/L); hematocrit, 42%; leukocyte count, 18,600 cells/µL (18.6 × 109 cells/L); platelet count, 520,000 cells/µL (520 × 109 cells/L); plasma glucose, 98 mg/dL (5.44 mmol/L); blood urea nitrogen, 18 mg/dL (6.43 mmol/L); and serum creatinine, 0.9 mg/dL (79.58 µmol/L). Serum electrolytes are normal.
A CT scan of the thigh shows a minute metallic fragment in the fascial plane just beneath the subcutaneous tissue and some stranding and edema in adjacent areas.
The patient is hospitalized, and empiric vancomycin is begun pending blood culture results. Three hours after admission, his blood pressure drops to 60/0 mm Hg. Vasopressors and intravenous fluid resuscitation are administered, and his blood pressure improves. Over the next several days, the patient develops signs of renal and hepatic insufficiency, but these gradually return to normal.
Which of the following is the most appropriate antimicrobial regimen at this time?
A. Vancomycin plus clindamycin
B. Nafcillin plus aztreonam
C. Nafcillin plus clindamycin
D. Nafcillin plus piperacillin–tazobactam
E. Piperacillin–tazobactam plus clindamycin
Case 3: Drug user in coma
A 59-year-old man is brought to the emergency department by friends because of impaired consciousness as well as pain, erythema and darkening skin of the left leg and thigh. The patient is now comatose and unable to give a history. However, records from earlier emergency department visits note that he is a long-time injection drug user (most often injecting intravenous heroin).
On physical examination, temperature is 39.9 °C (103.8 °F), pulse rate is 132 beats/min, respiration rate is 38 breaths/min and blood pressure is unobtainable. Necrosis of the skin and underlying soft tissue is present from the dorsum of the left foot to the mid-thigh.
Signs of injections into the dorsal veins of both feet are visible. Profuse crackles are present throughout the lung fields, and a grade 3/6 holosystolic murmur is heard that is loudest at the apex and radiates to the left axilla and cardiac base. No abdominal masses are palpated. The patient is unresponsive to any stimuli. There are no focal neurologic findings.
Laboratory values are as follows: hemoglobin, 9.9 g/dL (99 g/L); hematocrit, 29%; leukocyte count, 1,200 cells/µL (1.2 × 109 cells/L) with 92% neutrophils and 8% lymphocytes; platelet count, 78,000 cells/µL (78 × 109 cells/L); blood urea nitrogen, 55 mg/dL (19.64 mmol/L); serum creatinine, 4.1 mg/dL (362.52 µmol/L); serum sodium, 118 mEq/L (118 mmol/L); serum potassium, 6.9 mEq/L (6.9 mmol/L); serum chloride, 94 mEq/L (94 mmol/L); and serum bicarbonate, 12 mEq/L (12 mmol/L).
MRI of the left leg shows edema and gas in the subcutaneous tissues and muscles of the calf and thigh. Needle aspiration of the gastrocnemius muscle yields 1 mL of brown liquid that contains several neutrophils and many erythrocytes. A Gram-stained specimen of the liquid is negative. The patient is hospitalized.
Which of the following is the most appropriate initial antibiotic regimen?
A. Vancomycin plus metronidazole
B. Vancomycin plus piperacillin–tazobactam plus clindamycin
C. Piperacillin–tazobactam plus clindamycin plus doxycycline
D. Ciprofloxacin plus metronidazole plus nafcillin
Answers and commentary
Correct answer: C. Vancomycin
This patient has necrotizing fasciitis caused by community-acquired methicillin-resistant Staphylococcus aureus (MRSA). Community-acquired MRSA infections are endemic in prisons and in areas housing low-income populations, perhaps because of overcrowding. Early skin lesions are often described as a “spider bite.” Vancomycin is the drug of choice for these infections.
Although other antimicrobial agents such as trimethoprim–sulfamethoxazole and clindamycin may occasionally be used, they are less effective than vancomycin. If clindamycin is being considered, laboratory testing should be done first to determine susceptibility. If the causative organism is susceptible to clindamycin but resistant to erythromycin, the strain most likely has an inducible form of macrolide resistance, which makes clindamycin less effective. Ampicillin–sulbactam, cefazolin and oxacillin are effective for treating methicillin-susceptible S. aureus, but all ß-lactams are inactive against MRSA.
- Vancomycin is the antimicrobial agent of choice for treatment of methicillin-resistant Staphylococcus aureus infections.
- All ß-lactam agents are inactive against methicillin-resistant Staphylococcus aureus infections.
Correct answer: A. Vancomycin plus clindamycin
This patient probably has streptococcal or staphylococcal toxic shock syndrome and requires vancomycin and clindamycin. Vancomycin is indicated because of the prevalence of MRSA in the community. Clindamycin has been shown to improve survival in patients with toxic shock syndrome, presumably because of its effects on the production and release of toxin from bacteria and its antibacterial effects. Some experts would also add intravenous immune globulin because of its possible beneficial effects that presumably result from neutralization of the bacterial toxins elaborated by both staphylococci and streptococci. However, use of intravenous immune globulin remains controversial.
As long as Staphylococcus aureus is one of the possible pathogens, the other antibiotic regimens listed are not acceptable. Although nafcillin is an excellent drug for methicillin-sensitive staphylococci and hemolytic streptococci, it is not effective against MRSA. Aztreonam is effective only against aerobic gram-negative bacilli, which rarely cause toxic shock syndrome (and then only as a component of a mixed, synergistic infection). Although clindamycin alone may be useful in some patients, it may not be effective against all staphylococci and therefore should not be used until drug sensitivities are known. Piperacillin–tazobactam plus nafcillin is incorrect because neither drug is effective against MRSA. In addition, nafcillin is not needed with piperacillin–tazobactam because the latter agent is effective against streptococci and methicillin-sensitive staphylococci. Piperacillin–tazobactam plus clindamycin is incorrect because neither drug is effective against MRSA.
- Vancomycin plus clindamycin is the most appropriate empiric antibiotic regimen for a patient with suspected streptococcal or staphylococcal toxic shock syndrome.
Correct answer: B. Vancomycin plus piperacillin–tazobactam plus clindamycin
This patient has necrotizing fasciitis secondary to intravenous injection into the veins of the foot. The most appropriate initial antibiotic regimen is vancomycin plus piperacillin–tazobactam plus clindamycin. This regimen provides coverage for most organisms that would be expected to cause an infection in a drug user who is known to inject intravenous narcotics (i.e., Staphylococcus aureus, Streptococcus pyogenes and other hemolytic streptococci; aerobic gram-negative enteric organisms; Pseudomonas species; gram-positive and gram-negative anaerobic organisms; and miscellaneous pathogens). Vancomycin is effective against staphylococci, including MRSA, as well as various other gram-positive aerobic and anaerobic organisms. Piperacillin–tazobactam is effective against most of the expected gram-negative enteric pathogens, Pseudomonas species and anaerobic organisms, including Bacteroides fragilis. Clindamycin is useful for eradicating toxin-producing staphylococci and streptococci. Some experts would include an aminoglycoside, such as gentamicin, to provide added coverage of gram-negative organisms. Gentamicin would also have synergistic effects against gram-negative organisms and staphylococci.
Antibiotic combinations that are not listed could also be effective. However, the other three regimens given here have inadequacies that preclude their use. Vancomycin plus metronidazole provides no effective coverage for aerobic gram-negative organisms. Piperacillin–tazobactam plus clindamycin plus doxycycline is ineffective against MRSA. In addition, doxycycline is not needed because Vibrio vulnificus infection is unlikely in this injection drug user. Ciprofloxacin plus metronidazole plus nafcillin also does not provide coverage for MRSA. In addition, although fluoroquinolones are effective against many gram-negative enteric pathogens, these agents are less effective for coverage of unknown organisms.
- Necrotizing fasciitis in an injection drug user may be due to many different organisms.
- The most effective initial empiric antibiotic regimen for necrotizing fasciitis in an injection drug user is vancomycin plus piperacillin–tazobactam plus clindamycin.