A 47-year-old man who runs a yard service in Tallahassee cuts his thumb while attaching an accessory to one of his mowers. The next morning, his thumb is sore and the skin surrounding the cut is red. The man has thirty very impatient customers scheduled for lawn mowing that day so he heads out early and works until early evening. By the time he gets back home, the thumb is swollen and throbbing, and yellowish-white pus is oozing out of the injured area. He also notices two red streaks going up the inside of his forearm. Just as he begins to think about getting some medical attention for his thumb, the man experiences a shaking chill and becomes queasy. His wife then drives him to the ER at the nearest hospital, which takes about 35 minutes because of heavy traffic. Upon their arrival at the ER, the man's temperature has reached 39.7ºC. He is flushed and ill-appearing, with a pulse of 125 and a blood pressure of 100/60 mm Hg. (His normal BP is 145/85 mm Hg.) There are no other remarkable findings on physical examination.

Question 1.1: What is your preliminary diagnosis?

The combination of fever, tachypnea, and tachycardia suggests systemic inflammatory response syndrome (SIRS), which is usually defined as the presence of two or more of the following: (1) fever (> 38ºC) or hypothermia (< 36ºC); (2) tachypnea (R > 24/min); tachycardia (P > 90/min); and (4) leukocytosis (> 12,000/(l), leukopenia (< 4,000/(l), or >10% bands. SIRS can have an infectious or noninfectious etiology. In this case, there are obvious signs of microbial infection (pus oozing from a recent skin wound, fever), so a diagnosis of sepsis (i.e., SIRS with a proven or suspected microbial etiology) is justified. The patient has obvious hypotension in addition to the standard SIRS/sepsis symptoms, so he appears to have progressed to severe sepsis (defined as sepsis plus hypotension or one or more signs of organ dysfunction (metabolic acidosis, acute encephalopathy, oliguria, hypoxemia, or disseminated intravascular coagulation).

Question 1.2: What should you do right away?

This is a dangerous situation because the man could rapidly progress to septic shock (defined as sepsis with hypotension and organ dysfunction), which is often fatal. This patient's history and symptoms (e.g., pus formation) indicate that he almost certainly has a bacterial infection that is community acquired (i.e., not nosocomial in origin), so antibiotic therapy should be initiated as soon as possible. You do not know the identity of the causative agent at this time, so the safest course of action is to order an antibiotic regimen that can provide broad coverage of both Gram-positive and Gram-negative bacteria. (Because this is not a nosocomial infection, the causative agent is not overly likely to be highly resistant to antibiotics, but you can't be certain of this unless you run sensitivity tests.)

Question 1.3: What is the differential?

Much of the differential can be eliminated based on the patient's recent history and obvious evidence of microbial infection. If fever, tachypnea, tachycardia, and (possibly) hypertension were the only symptoms (as might occur if the patient had an internal infection that they were not yet aware of), the differential could include: cardiogenic shock, acute pancreatitis, systemic vasculitis, pulmonary embolism, toxic ingestion, exposure-induced hypothermia, fulminant liver failure, and collagen-vascular diseases.

Question 1.4: What tests should you perform?

Blood cultures should be ordered in hopes of identifying the causative agent. However, microbial invasion of the bloodstream (bacteremia) is not required for development of sepsis because local or systemic spread of microbial signal molecules or toxins can also provoke this response. Blood cultures yield bacteria or fungi in 20-40% of cases of severe sepsis (i.e., this case) and in 40-70% of cases of septic shock. If the lab manages to isolate and identify the causative agent, you will also want its sensitivity pattern. (It might be necessary or advisable to change the antibiotic treatment based on these lab findings.) You could also order a CBC with differential, to look for a left shift.

Test Results:

The lab isolates a Gram-positive coccus from the blood cultures. It is catalase positive and coagulase positive. The CBC shows WBC count of 14,575/microliter with differential 69 segs, 9 bands, 16 lymphs, and 6 monos, Hgb 14.1 g/dL, Hct 42.2%, MCV 90 fL, and platelet count: 230,000 per (L.

Question 1.5: What is the causative agent?

Staphylococcus aureus is the most likely causative agent. The positive catalase test eliminates Streptococcus and Enterococcus species, and the positive coagulase test essentially eliminates other Staphylococcus species. The production of yellowish-white pus also points to S. aureus.

Question 1.6: What are the most important causative agents overall?

Most cases of sepsis are caused by bacteria. Gram-negative bacteria (especially Pseudomonas aeruginosa, Escherichia coli, Proteus, Klebsiella, and Neisseria meningitidis) now account for about 40% of cases. Gram-positive bacteria (primarily Streptococcus, Staphylococcus aureus, and Enterococcus) cause about 30% of cases. Roughly 17% of cases are polymicrobial (mixed infections). Fungi (mostly Candida spp.) cause around 6% of cases.

Question 1.7: How prevalent is this disease?

It is estimated that 300,000 cases of sepsis occur each year in the U.S. About one third of these cases prove to be fatal.