1. Toxic Shock Syndrome
Jared Helms D.O.
7 March 2007

2. What Comes To Mind? Tampon use Minor trauma
Injuries resulting in hematoma, bruising, or muscle strain
Surgical procedures (eg, suction lipectomy, hysterectomy, vaginal delivery , bunionectomy, bone pinning, breast reconstruction, cesarean section)
Viral infections (eg, varicella, influenza)
Use of nonsteroidal antiinflammatory drugs
Childhood invasive GAS disease occurs at an incidence similar to the adult population but has a lower rate of STSS and case-fatality. Chickenpox dramatically increases the risk for acquiring invasive GAS disease, and universal chickenpox vaccination could potentially prevent up to 15% of all pediatric invasive GAS disease.
The association between NSAIDs and severe GAS infections is uncertain. The link may be attributable to the use of NSAIDs to relieve the symptoms of more severe trauma, which is a predominant risk factor. In a retrospective analysis of these cases, however, NSAIDs may have either masked the presenting symptoms, thus delaying a diagnosis, or predisposed to more severe streptococcal infection and shock [2]. Direct predisposition to GAS TSS by NSAIDs could be mediated via inhibition of neutrophil function, suppression of fever, and augmentation of cytokine release (eg, tumor necrosis factor)

3. What Comes To Mind? Cause Staphylococcus aureus (appx 0.8 per 100,000)
Group A streptococcus (appx 3.5 per 100,000)

4. Staphylococcal toxic shock syndrome
Term toxic shock syndrome was coined in 1978
Public attention in 1980 based upon a series of menstrual-associated cases
CDC proposed a revised clinical case definition in 1981
TSS associated with S. aureus was first described in a series of pediatric cases in 1978 [2]. The incidence of TSS rose sharply in 1980 when there were 812 documented cases of menses-related TSS. These cases occurred most commonly in young Caucasian women; Clinical illness arose during menstrual periods and was associated with the use of highly absorbent tampons. While the incidence of TSS sharply declined after the withdrawal of some brands of tampons, a slight increase in incidence of all TSS cases has occurred between 2000 and 2003 to 3.4 per 100,000 in one study. These estimates were in women of menstrual age but included both menstrual and non-menstrual cases and may represent increased recognition

5. Case definition of toxic shock syndrome from the CDC
Fever T >38.9°C (102.0°F)
Hypotension SBP< 90 mmHg; Orthostatic syncope or dizziness
Rash Diffuse macular erythroderma
Desquamation 1 to 2 weeks after onset of illness, particularly involving palms and soles

7. Case definition of toxic shock syndrome from the CDC
Multisystem involvement
(3 or more of the following organ systems)
GI: Vomiting or diarrhea at onset of illness
Muscular: Severe myalgia or CPK elevation >2 times the normal upper limit
Mucous membranes: Vaginal, oropharyngeal, or conjunctival hyperemia
Renal: BUN or serum creatinine >2 times the normal upper limit, or pyuria (>5 WBC/hpf)
Hepatic: Bilirubin or transaminases >2 times the normal upper limit
Hematologic: Platelets <100,000/ L
Central nervous system: Disorientation or alterations in consciousness without focal neurologic signs in the absence of fever and hypotension

8. Menstrual Between 1979 and 1996, 5,296 TSS cases were reported
59 percent from 1987 to 1996
number of cases of menstrual TSS to 1 out of 100,000 women since 1986
case-fatality rate was 1.8 percent in 1987 to 1996

9. Nonmenstrual
Approximately one-half of reported TSS cases are nonmenstrual
surgical and postpartum wound infections, mastitis, septorhinoplasty, sinusitis, osteomyelitis, arthritis, burns, cutaneous and subcutaneous lesions (especially of the extremities, perianal area, and axillae), and respiratory infections following influenza
The proportion of cases following surgical procedures increased from 14 percent in 1979 through 1986 to 27 percent in 1987 through 1996
Among all cases of TSS, 93 percent involved women, and 73 percent of nonmenstrual cases were in women [5]. However, in one study of 130 cases the distribution of cases between men and women was equal if vaginal and postpartum-associated cases were excluded

10. Menstrual versus nonmenstrual cases
Clinical presentations of menstrual and nonmenstrual TSS are similar
Nonmenstrual TSS was associated with earlier onset of rash and fever
Surgical wound sites and cutaneous infections are frequently benign-appearing without obvious purulence
The clinical presentations of menstrual and nonmenstrual TSS are similar. In one small study, nonmenstrual TSS was associated with earlier onset of rash and fever, more pronounced renal and CNS complications, and less musculoskeletal involvement [56]. Surgical wound sites and cutaneous infections that harbor toxin-producing S. aureus are frequently benign-appearing without obvious purulence

11. PATHOGENESIS
Toxic shock syndrome toxin-1 —initial exotoxin isolated from S. aureus isolates implicated in TSS in 1981
Enterotoxins A, C, D, E, and H
TSST1 is produced by 90 to 100 percent of S. aureus strains associated with menstrual cases of TSS and by 40 to 60 percent of strains associated with nonmenstrual cases.
Other enterotoxins, specifically enterotoxins A, C, D, E, and H have been implicated in a smaller number of cases.
Some investigators have postulated that other toxins may be more virulent than TSST-1; in one study of 32 S. aureus isolates from nonmenstrual TSS, five of 10 persons (50 percent) infected with a TSST-1 negative strain died, compared to only 2 of 20 (10 percent) with TSST-1 positive strains

12. PATHOGENESIS
S. aureus exotoxins cause disease because they are superantigens

13. Activate large numbers of T cells
Activated T cells then release interleukin (IL)-1, IL-2, tumor necrosis factor (TNF)-alpha and TNF-beta, and interferon (IFN)-gamma
Superantigens are molecules that are able to activate large numbers of T cells, often up to 20 percent of all T cells at one time, resulting in massive cytokine production [34]. In typical T cell recognition, an antigen is taken up by an antigen-presenting cell, processed, expressed on the cell surface in complex with class II major histocompatibility complex (MHC) in a groove formed by the alpha and beta chains of class II MHC, and recognized by an antigen-specific T cell receptor. By contrast, superantigens do not require processing by antigen-presenting cells but instead interact directly with the invariant region of the class II MHC molecule. Two regions of the TSST-1 toxin within the beta 1/beta 2 and beta 3/beta 4 loops have been found to be important for MHC class II binding [35]. The superantigen-MHC complex then interacts with the T cell receptor at the variable (V) part of the beta chain. Thus, all T cells with a recognized V beta region are stimulated.
IL-1 is an endogenous pyrogen and thus causes the high fevers associated with TSS. In addition, IL-1 mediates skeletal muscle proteolysis and probably accounts for the myalgia and elevated creatine phosphokinase (CPK) seen in TSS

14. Host antibody responses to the S
Host antibody responses to the S. aureus exotoxins play an important role in the pathogenesis of TSS
70 to 80 percent of individuals develop antibody to TSST-1 by the late teenage years, and by the fourth decade 90 to 95 percent have such antibody

15. Clinical manifestations of TSS are diverse based upon the action of the S. aureus toxin(s)
rapid onset of hypotension, often leads to subsequent tissue ischemia and organ failure.
can be unresponsive to large amounts of intravenous fluids and can persist for several days
The hypotension is caused by a decrease in systemic vascular resistance as well as nonhydrostatic leakage of fluid from the intravascular space to the interstitial space [45], both of which occur as a consequence of the massive cytokine release induced by the responsible toxins.

16. A variety of skin manifestations are seen in TSS
Initial erythroderma involves both the skin and the mucous membranes and is characterized by a diffuse, red, macular rash resembling sunburn that also involves the palms and soles
initial erythroderma involves both the skin and the mucous membranes and is characterized by a diffuse, red, macular rash resembling sunburn that also involves the palms and soles. This rash can be subtle and fleeting. The erythema may be more intense around the involved surgical wound site. Mucosal involvement includes conjunctival-scleral hemorrhage and hyperemia of the vaginal and oropharyngeal mucosa (show picture 2) [46]. In more severe cases, superficial ulcerations occur on the mucous membranes, and petechiae, vesicles, and bullae develop. Patients will also have non-pitting edema as a consequence of increases in interstitial fluid. Late-onset skin manifestations include a pruritic maculopapular rash that may occur one to two weeks after the disease onset and desquamation of the palms and soles that characteristically begins one to three weeks after illness develops (show picture 3). Since desquamation occurs late, the acute diagnosis of TSS cannot take advantage of this clinical feature. In fact, TSS may not even be considered in the differential diagnosis in some cases until later when desquamation is observed; this is particularly true in nonmenstrual disease [47]. Some patients also experience loss of hair and nails one to two months later with regrowth by six months

17. Multi system involvement
TSS can involve all organ systems
Many patients report diffuse myalgias and weakness as presenting symptoms
increase in serum concentrations of creatine phosphokinase
GI symptoms are also common
TSS can involve all organ systems. Many patients report diffuse myalgias and weakness as presenting symptoms, which are usually accompanied by an increase in serum concentrations of creatine phosphokinase (CPK). Gastrointestinal symptoms are also common, particularly profuse diarrhea.

18. Multi system involvement
Prerenal and intrinsic renal failure can occur
Metabolic abnormalities
Encephalopathy
Both prerenal and intrinsic renal failure can occur and are often accompanied by other metabolic abnormalities including hyponatremia, hypoalbuminemia, hypocalcemia, and hypophosphatemia [51].
Encephalopathy, manifested by disorientation, confusion, or seizure activity, can be a presenting symptom of TSS [52] and is probably due to cerebral edema

19. Laboratory findings Leukocytosis may not be present
total number of mature and immature neutrophils usually exceeds 90 percent
immature neutrophils accounting for 25 to 50 percent of the total number of neutrophils
Thrombocytopenia and anemia
Abnormalities in clinical laboratory tests will reflect shock and organ failure. Leukocytosis may not be present, but the total number of mature and immature neutrophils usually exceeds 90 percent, with immature neutrophils accounting for 25 to 50 percent of the total number of neutrophils. Thrombocytopenia and anemia are present during the first few days, frequently accompanied by prolonged prothrombin and partial thromboplastin times. Disseminated intravascular coagulation may be present.
Other laboratory abnormalities reflect multiorgan failure with elevated blood urea nitrogen and creatinine, elevated liver function tests, and an elevated creatine phosphokinase [51,59,60]. Most laboratory tests will return to normal within seven to 10 days after disease onset.

20. DIAGNOSIS Based upon clinical presentation
Isolation of S. aureus is not required for the diagnosis of staphylococcal TSS
Cultures from mucosal and wound sites should be obtained
To meet the CDC case definition for a confirmed case, patients must have fever >38.9ºC, hypotension, diffuse erythroderma, desquamation (unless the patient dies before desquamation can occur), and involvement of at least three organ systems
Although 80 to 90 percent of TSS patients have S. aureus isolated from mucosal or wound sites [57], the isolation of S. aureus is not required for the diagnosis of staphylococcal TSS. In contrast to streptococcal TSS, S. aureus is only rarely (5 percent) recovered from blood cultures
Cultures from mucosal and wound sites should be obtained because S. aureus isolates can be tested for toxin production in research laboratories. In addition, these laboratories can analyze acute and convalescent serum for antibody responses to various S. aureus exotoxins. The presence of a strain of S. aureus that produces toxin in a patient who does not have acute phase antibody to the toxin is highly suggestive of TSS.

21. DIFFERENTIAL DIAGNOSIS
Streptococcal TSS
associated with severe pain and tenderness signifying infection at a site of local trauma
Rocky Mountain spotted fever
the rash associated with RMSF typically is petechial, involves the extremities first
Meningococcemia
meningitis is frequently seen in conjunction with meningococcemia and is rare in TSS
Other more unusual illnesses can be considered if there is an appropriate exposure such as leptospirosis, dengue hemorrhagic fever, and typhoid fever
In addition to the aforementioned illnesses, the differential diagnosis for patients with suspected nonmenstrual TSS should include nosocomially-acquired sepsis from gram-negative or gram-positive pathogens. These organisms should be recovered in blood cultures to make a diagnosis; the type of bacterium isolated may provide a clue about the origin of the infection.

22. MANAGEMENT Mainstay of treatment for TSS is supportive
may require extensive fluid replacement (10 to 20 liters per day) to maintain perfusion
vasopressors may also be required
Episodes of menstrual TSS can resolve with supportive care only
Patients may require extensive fluid replacement (10 to 20 liters per day) to maintain perfusion because of intractable hypotension and diffuse capillary leak. Although the blood pressure may improve with fluids alone, vasopressors (eg, dopamine and/or norepinephrine) may also be required.

23. MANAGEMENT
Examination for the presence of foreign material in the vaginal canal
Drainage of any identified infectious focus
Surgical wounds may not appear to be infected because of the decreased inflammatory response but should nevertheless be explored and debrided if the patient fulfills the clinical criteria for TSS.

24. MANAGEMENT
It is not clear whether antibiotics alter the course of acute TSS, however antistaphylococcal antibiotic therapy is needed to eradicate organisms
Theoretically, antibiotics such as clindamycin that suppress protein synthesis and, therefore, toxin synthesis may be more efficacious than cell wall active agents such as beta-lactams. This finding has been demonstrated in vitro; subinhibitory concentrations of clindamycin, erythromycin, rifampin, and fluoroquinolones suppressed TSST-1 synthesis by 90 percent, while five different beta-lactam antibiotics, including nafcillin and cephalosporins, increased measurable TSST-1 in culture supernatants, probably by lysis or increasing cell membrane permeability

25. Antibiotic therapy
All patients with suspected TSS receive empiric treatment with clindamycin (adults: 600 mg IV every eight hours; children: 25 to 40 mg/kg per day in three divided doses) plus vancomycin (adults: 30 mg/kg per day IV in two divided doses; children: 40 mg/kg per day IV in four divided doses)
Typically treat with a 10 to 14 day course
While clindamycin may be adequate single drug therapy for a drained infected focus such as a surgical wound, we recommend combination therapy of clindamycin and an antistaphylococcal penicillin (eg, oxacillin or nafcillin) or vancomycin for patients with deep-seated infections (eg, osteomyelitis) or bacteremia. Antibiotic therapy clearly reduces the likelihood of recurrent TSS by eliminating the carrier state [57
Corticosteroids — Some investigators have advocated the use of high dose corticosteroids (methylprednisolone 10 to 30 mg/kg per day) for TSS [73]. In a retrospective study in which 25 patients who received steroids were compared to 20 patients who did not, patients treated within two to three days of the onset of TSS had reduced severity of illness and duration of fever, although there was no difference in mortality. We do not recommend corticosteroid treatment in TSS because of the limited clinical data with this therapy.

26. Staphylococcal toxic shock syndrome?
PROGNOSIS
Death associated with TSS usually occurs within the first few days of hospitalization but may occur as late as 15 days after admission
Questions about
Staphylococcal toxic shock syndrome?

27. Group A streptococcus TSS
Defined as any GAS infection associated with the acute onset of shock and organ failure
Any infection associated with the isolation of GAS from a normally sterile body site
aerobic gram-positive coccus that causes pharyngitis and a spectrum of skin and soft tissue infections such as impetigo, erysipelas, and localized cellulitis

28. PATHOGENESIS
Group A streptococcal TSS is mediated by toxins that act as superantigens
Cytokines cause capillary leak and tissue damage, leading to shock and multiorgan failure

29. PATHOGENESIS
Most common portals of entry for streptococcal infections are the skin, vagina, or pharynx
Portal of entry cannot be identified in 45% of cases
These patients frequently develop deep seated infections such as necrotizing fasciitis within 24 to 72 hours at the exact site of minor trauma such as a bruise, strained muscle or sprained ankle, frequently without a visible break in the skin.

30. CLINICAL PRESENTATION
Most common initial symptom is severe pain
abrupt in onset
diffuse or localized
typically involves an extremity
may also mimic peritonitis, pelvic inflammatory disease, pneumonia, acute myocardial infarction, cholecystitis, or pericarditis
Fever is the most common presenting sign
hypothermia may be present in patients with shock

31. Other manifestations 80 % clinical signs of soft tissue infection
influenza-like syndrome (20%)
fever, chills, myalgia, nausea, vomiting, and diarrhea
50% of patients are normotensive on presentation or admission, but become hypotensive within the subsequent four hours.
Shock — Shock at the time of admission or within four to eight hours is present in virtually all patients with GAS TSS and is due both to capillary leak and vasodilatation. Despite aggressive therapy, the systolic pressure remains depressed in 90 percent of patients after eight hours [2].
Complications — The complications of GAS TSS are severe. They include bacteremia, acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation, renal failure [38], and rarely Waterhouse-Friderichsen syndrome [40].
Renal dysfunction is present in all patients by 48 to 72 hours and many patients require dialysis for 10 to 20 days. In patients who survive, the serum creatinine concentration returns to baseline within four to six weeks.
ARDS occurs in approximately 55 percent of patients, generally developing after the onset of hypotension [2]. Almost all patients with ARDS require supplemental oxygen, intubation, and mechanical ventilation. (See "Acute respiratory distress syndrome: Definition; epidemiology; diagnosis; and etiology").

32. Laboratory findings Mild leukocytosis
percentage of immature neutrophils may reach 40 to 50 percent
Serum creatinine is frequently elevated
precedes the development of hypotension in 40 to 50 percent of cases
Myoglobinuria and hemoglobinuria
can contribute to the development of acute renal failure

33. Laboratory findings Increase in the serum creatinine kinase
suggests the presence of necrotizing fasciitis or myositis
Positive blood cultures
approximately 60 % of cases (5% in Staph TSS)

34. DIFFERENTIAL DIAGNOSIS
Staphylococcal toxic shock syndrome
Gram-negative sepsis
uncommon in healthy patients outside the hospital setting
Rocky Mountain spotted fever
severe headache and rash are present in most patients with RMSF; rash is present in only 10% of patients with GAS TSS
Acute meningococcemia
rash is petechial and meningitis is common in meningococcemia but is infrequent in GAS TSS

35. DIAGNOSIS Isolation of GAS from a normally sterile site
Hypotension (systolic blood pressure 90 mm Hg in adults )
Plus two or more of the following:
Renal impairment
Coagulopathy
Liver involvement
Erythematous macular rash, may desquamate
Soft tissue necrosis
DIAGNOSIS — GAS TSS must be considered in any patient presenting from the community in shock. A history of recent trauma and severe pain and fever favor a diagnosis of GAS TSS.
The Working Group on Severe Streptococcal Infections established the following clinical guideline for diagnosis of GAS TSS [19]:
Isolation of GAS from a normally sterile site (eg, blood cerebrospinal, pleural, or peritoneal fluid, tissue biopsy, or surgical wound) plus
Hypotension (systolic blood pressure 90 mm Hg in adults or <5th percentile for age in children)
plus two or more of the following:
Renal impairment (creatinine in adults, 2 mg/dL; in children, two-times upper limit of normal for age; in patients with pre-existing renal disease two-fold elevation over baseline)
Coagulopathy (eg, thrombocytopenia, disseminated intravascular coagulation)
Liver involvement (eg, two-times upper limit of normal for age of transaminases or bilirubin; in patients with pre-existing liver disease two-fold elevation over baseline)
Adult respiratory distress syndrome
Erythematous macular rash, may desquamate
Soft tissue necrosis (eg, necrotizing fasciitis, myositis, or gangrene)
If GAS is isolated from a nonsterile site (eg, throat, vagina, skin lesion) but the patient fulfills the other criteria noted above, a diagnosis of probable GAS TSS can be made if no other etiology for the illness is identified.
Recovery of the organism from blood cultures usually takes from 8 to 24 hours. When surgery is performed for debridement of infected fascia or muscle, Gram's stain of involved tissue showing gram-positive cocci in pairs and chains provides an early and definitive diagnosis in the vast majority of cases.

36. Treatment Hemodynamic support Surgical therapy
Massive amounts of intravenous fluids (10 to 20 L/day) are often necessary
vasopressors may also be required
Surgical therapy
Prompt and aggressive exploration and debridement of suspected deep-seated infection is mandatory
It is critically important that surgeons be involved early in such cases, since surgical intervention may be impossible later in the course due to toxicity or because infection has extended to vital areas that are difficult to debride (eg, head and neck, thorax, or abdomen). Surgical debridement may be too late by the time the patient develops systemic toxicity and definite evidence of necrotizing fasciitis or myositis. Surgical exploration through a small incision with visualization of muscle and fascia and Gram's stain of involved tissue may provide an early and definitive diagnosis

37. Treatment Antibiotic therapy
Presumptive therapy should be initiated pending culture results
Clindamycin suppresses the synthesis of bacterial toxins and suppresses TNF
The role of IVIG in GAS TSS remains to be determined by controlled trials.
Choice of antibiotic therapy — Definitive studies, which establish the most effective antibiotic regimen in treating GAS TSS, are not available. A retrospective review of the outcome of treatment of 56 children with invasive GAS infections found that a favorable outcome was statistically more likely in patients who received a protein synthesis-inhibiting antibiotic (eg, clindamycin) compared to those who received only a cell wall-inhibiting antibiotic (eg, beta-lactams) (83 versus 14 percent with beta-lactams had a favorable outcome) [19].
We recommend empiric therapy, for an adult who presents with the clinical manifestations of GAS TSS prior to the identification of GAS by culture, with broad-spectrum antibiotics such as:
Clindamycin (900 mg IV every eight hours)
plus one of the following:
A carbapenem (eg, imipenem 500 mg every six hours or meropenem 1 g every eight hours)
A combination drug containing a penicillin plus beta-lactamase inhibitor (eg, ticarcillin-clavulanate 3.1 g every four hours or piperacillin-tazobactam 4.5 g every six hours)

38. Recommended Empiric Therapy
Clindamycin (900 mg IV every eight hours)
plus one of the following:
A carbapenem (meropenum 1g every eight hours)
A combination drug containing a penicillin plus beta-lactamase inhibitor (eg, ticaracillin-clavulanate 3.1 g every four hours or piperacillin-tazobactam
4.5 g every six hours)
Duration of therapy — There are no clinical studies addressing the optimal duration of antibiotic therapy in GAS TSS. We recommend that the duration of antibiotic therapy be individualized. Patients who are bacteremic are treated for a minimum of 14 days. In patients with complicating deep-seated infections, such as necrotizing fasciitis, length of therapy depends on the clinical course; therapy is usually continued for 14 days from the last positive culture obtained during surgical debridement.

39. PROGNOSIS
Overall mortality rate in GAS TSS varies from 30 to 70 percent
Signs of poor prognosis*:
Lower white blood cell count (1000 vs 16000)
Lower platelet counts (120 vs 170)
Higher serum creatinine (3.0 vs 2.0)
Lower systolic blood pressure (99 vs 120)
The overall mortality rate in GAS TSS varies in different series from 30 to 70 percent [2,27,36-38]. Mortality rates are lower in children than adults, with a mortality rate of 18 percent reported in one series [39].
A retrospective study of 66 patients with GAS TSS (30 who died and 36 who survived) in Japan, compared physical and laboratory findings on admission that differentiated survivors from those who died [38]. The following statistically significant findings were noted in patients who died:
Lower white blood cell (WBC) count (mean WBC count, 1000 cells per microL in those who died versus 16,000 cells per microL in survivors)
Lower platelet counts (mean platelet counts, 120,000 per microL in those who died versus 170,000 per microL in survivors)
Higher serum creatinine (mean 3.0 versus 2.0 mg/dL in survivors)
Lower body temperature (mean 37.0 versus 38.3 ºC)
Lower systolic blood pressure (mean 99 versus 120 mmHg)

40. Review Toxic shock syndrome is bad Fortunately, it is uncommon
Treat hypotension with lots of fluids
Surgical debridement should be considered early
Clindamycin is the drug of choice

41. A 29 year old man comes to the ER with 1 day history of increasing pain in the upper right thigh. Two days ago, he was cutting rebar with a power saw when he suddenly developed right thigh pain from a splinter thrown by the saw. The pain abated over the next hour, and there was no lesion when he examined the thigh that evening. PMH is unremarkable. On physical exam vitals are 96/ The right thigh is moderately tender. There is no erythema or swelling.

42. CT scan shows a minute metal fragment in the facial plane beneath the subcutaneous tissue with edema and stranding in adjacent areas.
The patient is hospitalized and begun on empiric vancomycin pending culture results. Three hours after admission, his BP drops to 60/0. IV fluids and vasopressors are started with mild improvement in pressure. Over the next several days the patient develops signs of renal and hepatic insufficiency (gradually returns to normal).

43. Armed with the knowledge of a stellar noon-time lecture you astutely diagnose:
Cellulitis
Staphylococcal toxic shock syndrome
Streptococcal toxic shock syndrome
Adverse reaction to vancomycin

44. 2. Management of this patient includes:
Continue vancomycin and increase fluids
Switch to clindamycin and nafcillin
Add clindamycin to the vancomycin and get a surgical evaluation
Have him (or DPOAHC) fill out DNR papers

45. 3. When grilled on rounds about the incidence of this infection, you confidently answer:
0.8 cases per 100,000
3.5 cases per 100,000
“It’s actually pretty common”
Million to one shot doc