Medical School 2020, Year 2, Week 1

From our anonymous insider…

We gathered at a Sunday barbecue before our first day of the second year. We won’t expect to see too much of Awkward Allen because he married a business consultant who works two hours away and moved in with his wife. Although several students toiled away in our research labs over the break, most people took at least a short vacation. The young father whose wife is in law school jetted off to Europe: “our first vacation since the baby was born eight months ago.” Baby was parked with the grandparents for two weeks. Two classmates coincidentally were both on separate vacations with parents and siblings to Peru. They took different approaches to anthropology. One camped in the mountains among the Inca ruins. The other reported, “the alcohol is so cheap there. Our family’s whole tab for a week was seventy bucks!”

We’re nervous about this block, covering clinical microbiology (everything that can cause an infection: bacteria, viruses, fungi, parasites, autoimmune disorders). All of last year’s blocks were centered around a single physiology textbook. We’ll be using a diversity of materials, many self-selected, for microbiology. About a fourth of students started researching textbooks and studying during the break. The general consensus of upperclassmen, based on the class Facebook and Group-Me chat, is to use Sketchy Micro. These are a video series of narrated progressive illustrations. For example, they will draw a cat for bacteria that are catalase-positive, or draw a van for bacteria that the recommended antibiotic treatment is vancomycin. In our new small-groups, some students close their eyes to imagine the illustration. It seems odd, but it works for them. So far I’m just using a textbook: Medical Microbiology by Murray.

Reflecting modern education’s prioritization of bureaucracy over academics, M2 opened with an hour-long orientation led by two deans, experts on paperwork for the LCME. This year will be clinically-focused in comparison to last year’s emphasis on basic science. This will prepare us for the rotations of M3 and M4, our “clerkship years.” We need to be able to conduct a full history and targeted physical exam, then present this to our attending or resident with our differential diagnoses. Most lectures will be conducted by practicing clinicians, instead of PhDs, requiring scheduling flexibility on our part.

Our first lecture began on Monday at 9:00 am, right after the orientation. An Emergency Medicine physician in his mid-thirties specializing in the management of sepsis kicked off what promises to be a jam-packed two weeks of bacteriology. Our textbooks give the illusion that the moment you send a sample (e.g., blood, stool, urine, or sputum) off to the “Lab”, the identity of the bacteria is immediately ascertained. “When I have a potential septic patient in the ED, I do not have two days to wait to grow a culture. Instead, I will get back a few key findings in maybe two hours before the full report. The prelim report will give me Gram-staining. If the identified bacteria is Gram-positive they will also run a quick catalase enzyme activity.” I was excited to check the Google Calendar and see that he is returning for two more lecture this week. My female classmates were also excited, characterizing our lecturer as “dreamy.”

Afterwards, a 45-year-old lab technician from Quest Diagnostics came in with three boxes of samples to lead a workshop. He explained how he runs 10 of the tests that we might order. He opened with a colony of methicillin-resistant staphylococcus aureus (MRSA), the bacteria that causes pneumonia, sepsis, endocarditis, and skin infections, and ran a quick catalase test. The petri dish had small transparencies in the agar gel demonstrating MRSA’s ability to lyse red blood cells. He took a swab, swiped a colony on the petri dish and put some hydrogen peroxide on the swab. We saw it start bubbling up. “Now you know it is MRSA, and not Strep.” He showed us two McConkey growth plates where a colony of pink lactose-fermenting, harmless E Coli contrasted with a dull-yellow strain of Salmonellae. Students afterwards commented, “He knew a lot, and this was a perfect complement to the theory, but I wish he would stop waving that swab around. I don’t want to catch MRSA!”

Lectures afterwards delved into the main categories of bacteria defined by the Gram stain. Gram-positive bacteria have a thick outer peptidoglycan (sugars cross-linked with short peptide bridges) cell wall outside its cell membrane; Gram-negative bacteria have an additional outer lipid membrane covering its thinner cell wall. This key difference, specifically the presence or absence of a second cell membrane, will affect the virulence (ability to cause disease) and susceptibility to various antibiotics.

We learned that there is a fine line between hosting normal bacterial flora and being on the verge of death from infection. For example, Streptococcus pneumoniae, the most common cause of bacterial pneumonia, is a normal component of the oropharynx and throat. Pneumonia ensues when oropharynx secretions are aspirated (entry into larynx and respiratory tract) and the protective mucous lining of the upper respiratory tract is diminished by IgA protease secretion. The “flesh-eating” bacteria, Streptococcus pyogenes is also the culprit of the common strep throat in children. S. pyogenes produces many virulent proteins that enable its spread but induce a strong immune response. M-protein on its cell wall prevent phagocytosis, but elicits a strong antibody response. Sometimes, S. pyogenes release streptolysins and pyrogenic exotoxins that lead to Scarlet Fever or potentially Toxic Shock Syndrome from systemic activation of the immune system. The surge of antibodies produced during a S. pyogenes infection can lead to Rheumatic Fever (involving heart inflammation) and Post-Strep Glomeuruloar Nephritis (inflmmation of kidney from small immune deposits). According to the  American Academy of Family Physicians, “Although antibiotics have been shown to reduce the severity of acute symptoms and shorten the duration of the illness by about one day, more than 90 percent of treated and untreated patients with acute pharyngitis are symptom-free by day 7. Therefore, the primary reason for treating uncomplicated streptococcal pharyngitis is to markedly reduce the incidence of subsequent rheumatic fever” and other serious complications. Many people, especially if they work in healthcare, host Staphylococcus aureus in peaceful colonies on their skin. A small cut or abrasion in the skin can let Staph in where it will usually cause a benign skin infection, but sometimes can lead to release of Staphylococcal Toxic Shock Syndrome Toxin. This toxin, called a superantigen because it can lead to activation of twenty percent of T-cells, endothelial cell dysfunction, and shock. If the strain is methicillin-resistant (MRSA), treatment is vancomycin to kill the bacteria, and fluids, vasopressors, and blood transfusions to address the life-threatening symptoms of shock.

Our best defense against harmful bacteria seems to be other bacteria. Our body realized that we cannot beat them, so instead our immune system attempts to supervise the ecosystem. Numerous surfaces skin, oral cavity, gut, urogenital canal are colonized with competing bacteria that prevent any single one from domination (most antibiotics are copies of compounds secreted by one bacteria to inhibit the growth of another). Some of the worst infections occur when the entire ecosystem is wiped out after administration of a broad-spectrum antibiotic. Babies are vulnerable due to immature flora and immune systems, which is why women in the 35th week of pregnancy are screened for vaginal colonization of Streptococcal agalactiae (group B strep). If the baby picks up S. agalactiae during delivery, it could lead to bacteremia (bacteria in the blood), pneumonia, and meningitis.

The EM physician emphasized that the physiological response to an infection is not necessarily indicative of the degree of colonization. “Infection is just one component of septic shock.” Septic shock occurs from the immune system’s overreaction to an unwelcome guest. In fact, gastroenteritis can even be caused without eating a food infected with staphylococcus. If staphylococcus had ever been colonized in the food, it could deposit toxins that are resistant to heat and cold. “The bacteria could be long gone from a contained piece of food and cause severe gastroenteritis even if nothing is colonizing the gut. Simply the immune system reaction is enough.” Antibiotics do not help against toxins.

Our patient case: Ellie, a 30-year-old female, was vacationing with a group in the Caribbean a year earlier. Ten group members got diarrhea after eating ice cream. After three days of symptoms, she and her husband went to a clinic where they waited briefly until the doctor showed up on a moped. The doctor explained that they didn’t normally give meds for these symptoms, but the husband insisted and Ellie received a single dose of an unknown antibiotic. Her GI symptoms improved after three days, but four days later she developed general malaise, 102-degree fever, myalgia (muscle pain), petechiae (small diffuse red specks on the skin) and hemoptysis (coughing up blood). Ellie made it home, but these symptoms persisted for two weeks. Her primary care doctor referred her to an infectious disease (ID) specialist for further evaluation.

The ID physician, who did his residency in Ghana seeing nasty infections every day, explained, “This case really perplexed me. It was not a typical presentation nor clinical course.” She was put on a seven-day course of levofloxacin for suspected Typhoid fever. A blood culture came back normal, but her stool sample revealed a non-typhoid fever strain of salmonella, a bacteria that infects the gut immune system. Typhoid-causing salmonella is distinguished by a short DNA piece. This gene island allows the bacteria to hitch a ride with macrophages to infect organs beyond the gut. Despite the antibiotic treatment covering salmonella, her symptoms did not improve. “I was convinced I had dengue fever. There was a CDC warning about it,” explained Ellie. This fear was compounded because the ID doctor was uncertain about his diagnosis. “It can take up to a week after this treatment for symptoms to get better. Throughout the whole experience I was not sure her constitutional symptoms were due to the salmonella infection. Typically a non-typhoidal strain would be constrained to gastroenteritis which according to HPI [history of present illness] resolved quickly.” On day seven, when he was going to re-evaluate her diagnosis and start her on another antibiotic treatment, her fever resolved. The ID physician hypothesized that the initial antibiotic dose may have caused Ellie’s more serious problems by disrupting her ordinary bacterial flora.

The most surprising aspect of the case was that Ellie told us that she’d just returned from the same Caribbean island: “I did not go to the same ice-cream shop.”

Statistics for the week… Study: 10 hours. Sleep: 8 hours/night; Fun: 2 days. Example fun: Jane and I joined Lanky Luke and his PA wife Sarcastic Samantha for a late afternoon beach-music concert followed by burgers at their pristine apartment. Samantha, in her final rotations at PA school, recently returned from her eight-week ED rotation in two nearby counties. “What shocked me about my ER rotation was that the docs are paid per patient and PAs are salaried. To maximize profit, all time-consuming procedures (e.g., central lines) are done by PAs. The result is that doctors tend to see the green triage patients [the least serious cases] while the PA is working with the yellow triage group. It just didn’t make sense.”