From our anonymous insider…
Three marathon 4-hour lecture sessions with infectious disease (ID) specialists. Some would cover over 10 different diseases caused by a specific bacterial strain in a mere hour time. Most of the information went in one ear and out the other, especially with the PhD microbiologists. About two-thirds of students stopped attending lecture after the first session. “I have to study this material on my own over several days to not suffer from information overload. I do not find getting bombarded at lecture is efficient use of my time.” They missed a few clinical pearls from the more lively ID clinicians.
One ID doctor delved into the disease-filled, gram-positive, spore-forming, anaerobic genus Clostridium. Spores enable a bacterium to lay dormant, surviving external pressures such as extreme temperatures, pH, and sanitation chemicals. C. difficile is able to survive hand sanitizer and many hospital disinfectants. “Only thorough hand washing will get C diff off your hands. Hand sanitizer does nothing to it.” C diff jumps from bed to bed in hospitals, causing terrible gastroenteritis. Although C. diff is not able to thrive against normal gut flora, after a broad-spectrum antibiotic that decimates the normal flora, C diff will overtake the gut leading to pseudomembranous colitis and the release of toxins that cause life-threatening rice-water diarrhea similar to cholera. The genus Clostridium also contains C. tetani and C. botulinum two related species that cause tetanus and botulism, respectively. C. tetani produces a neurotoxin that destroys inhibitory neuron activity producing a spastic paralysis, typified by lock-jaw. Why are rusty nails and dog bites associated with tetanus? The skin typically seals over a deep penetrating wound before it is fully repaired. Sealed off from the destructive power of oxygen, anaerobic bacteria such as Clostridium tetani thrive. C. botulinum produces a similar neurotoxin, classified as a Tier I bioterrorism agent, that destroys neuromuscular junction activity, producing a flaccid paralysis. Otto Warmbier, the University of Virginia student imprisoned by North Korea, contracted botulism, which lead to respiratory arrest and coma. (The same Botulinum Toxin, “Botox,” can be harnessed to extend the expiration date of the Hollywood elite.)
A 35-year-old overweight unkempt ID pharmacist and an internal medicine resident led a highly effective two-hour lecture and workshop. Unlike the pharmacist at your local Walgreens, pharmacists who work in hospitals must complete a residency. Our lecturer said that his job was to eliminate any bug that comes into his hospital. He went over the clinical impact of antibiotic resistance: “the never-ending arms race.” “My job is to make you good stewards of antibiotics. Now, this can seem like a daunting task, especially when Cipro [broad-spectrum antibiotic] is OTC in Mexico, but let’s give it a shot.” The ID pharmacist added his opinion that there are few new antibiotic classes in the pharmaceutical pipeline because it is difficult to make a profit: “In addition to costing millions to bring a new drug to market, once it is in market, bacteria develop resistance so fast that it doesn’t have a long shelf-life. Further, the medical system reserves new antibiotics as a last line defense.” A student shared a Harvard-Technion experiment on the class GroupMe illustrating the rapid generation of antibacterial resistant genes. Escherichia coli with a fluorescence probe was plated on one end of a giant agar plate with steps of increasing concentrations of the antibiotics trimethoprim (Bactrim) or ciprofloxacin A time-lapse video depicts bacterial colonies traversing onto each step and completely covering the sheet by 12 days.
The 27-year-old internal medicine resident, reminded us that Group A Strep (strepococcal pyogenes) is one-hundred percent sensitive to penicillin. “Don’t be a jerk and give your poor patient a Z-pack,” she cautioned. [Azithromycin is a broader-spectrum antibiotic.] We were also informed that hospitals in different regions have different antibiotic schedules: “MRSA is much more rare in rural Idaho than in NYC. I would be terrified to get hospitalized in NYC.”
The workshop culminated in using iPads to play “Heads Up”. One student would put the iPad on his or her head and, based on hints from other group members, try to guess the bacterium or antibiotic displayed on the screen, e.g., 1st-generation cephalosporin or Clostridium tetani.
My favorite lecture was by a 35-year-old emergency medicine physician on the management of sepsis, a systemic immune response to infection. The immune response causes blood vessels to dilate, thus reducing blood pressure (hypotension), leading to multiple organ failures (“septic shock”). Patients who show up in the ED with septic shock have a mortality rate of twenty-five percent. “I like how he made you feel like you were in the ED. He gave so many different clinical cases,” commented a student after class.
The physician explained, “If a patient is in shock, I immediately conduct a RUSH (Rapid Ultrasound for Shock and Hypotension) exam. I am looking for what is causing the shock. Is it an internal bleed causing blood to pool in Morison’s Pouch [between kidney and liver] or around the rectum? Is it cardiac tamponade [fluid in the sac of the heart restricting its motion]?” Once he has determined septic shock, he starts the patient on antibiotics even without any confirmation of bacterial infection. He then determines if the patient is fluid-sensitive, i.e., if cardiac output would improve with IV saline. The Starling Curve describes cardiac output as a function of End Diastolic Volume (blood volume) for a given heart contractility and vascular tone. The physician continued, “We used to just give the standard 30mL/kg. [2 L for a 70 kg person.] Now electrical engineers have given us the NICOM [Non-invasive cardiac output monitoring] device to determine if someone is fluid-sensitive or insensitive.” NICOM device uses two pairs of electrodes to measure the change in impedance across the chest to the abdomen as a bolus of fluid is injected into the patient. He concluded, “No idea how it works, but we use it everyday. It is pretty neat to see the Frank Starling Curve appear on the NICOM screen and watch the physiology we learn in medical school actually be applied.”
Our patient case: A young ED physician describes his treatment of Abigail, a 26-year-old waitress attending community college for interior design. She presents to the ED for a worsening blood-tinged productive cough, fever, syncope (fainting episodes), and back pain. Over two months she has been to the ED twice and been prescribed different antibiotics for a productive cough and myalgia. With blood pressure of 80 over 55 and heart rate of 110, she is immediately recognized to be in shock and is transferred to the ICU. The RUSH exam reveals left ventricular dysfunction suggestive of distributive shock (leaky blood vessels from suspected sepsis infection decreasing blood volume). Even after a total of two liters of IV saline, she requires pressors (norepinephrine) to maintain a MAP (mean arterial pressure) above 65 mmHg.
“Her entire course changed from a simple question: ‘Do you use drugs?’,” explained the ED physician. Abigail confirmed she regularly injects oxycodone into her veins. “We immediately suspected septic shock with endocarditis [infection of heart tissue] likely from Staph aureus, which has a proclivity to infect the tricuspid valve after getting injected into the blood.” Blood and sputum cultures grew methicillin-resistant Staphylococcus aureus (MRSA). She is immediately started on IV vancomycin (a non-penicillin-based antibiotic reserved for serious gram-positive hospital infections). Echocardiography reveals substantial vegetation on the tricuspid valve. The colonies were releasing small particles into her pulmonary circulation causing septic pulmonary emboli. In addition to heart and lung colonization, she developed osteomyelitis (bone infection) in her vertebrae. The immense immune response due to the bacteremia (infection in blood) and Staph aureus toxins caused glomerulonephritis (kidney inflammation) and hematuria (blood in urine).
“Although the bacteria is the cause of her sepsis, the infection was not the immediate concern,” explained the EM physician. Intensive support therapy including blood/plasma transfusions, fluids, mechanical ventilation, and vasopressors were given throughout her two-week ICU stay. “I’ve rarely seen someone recover completely in medicine after septic shock with tricuspid valve endocarditis. It truly amazes me. Heart, lung, kidney—all fully recovered except for lower back pain.” Abigail was transferred to a “step down” unit [in between the ICU and the general ward] and discharged to rehab.
When we returned to lecture, an ID physician introduced diseases of the spirochetes such as Syphilis and Lyme Disease. “Always note the presence of rash on the palms or soles.” This can help narrow down a broad differential as not many diseases cause a rash there. Syphilis, caused by Treponema pallidum, begins with formation of a chancre, a characteristic painless ulcer, on the penis or in the vagina that lasts for four-six weeks. “I can never understand how some males do nothing about this quite obvious lesion.” Patients then develop a generalized lymphadenopathy (enlarged or sensitive lymph nodes) with a diffuse rash on the palms and soles that resolves. After a multi-year latency period (typically within 5 years of primary infection or 15-20 years after primary infection), some patients enter a serious tertiary phase that involve syphilitic aortitis (inflammation of the aorta potentially causing an aortic aneurysm ), neurosyphilis and gummas (red protrusions of the skin with a necrotic core).
Lyme disease, caused by Borrelia burgdorferi, requires an infected tick to be feeding on the human for at least 48 hours for the bacteria to change membrane proteins in preparation for human cell infection. The feeding ticks are typically less than two millimeters in size, so they are easier to miss than a syphilis chancre. Lyme-infected ticks and diseased humans are most common in the Northeast and upper Midwest, coinciding with large deer populations.
Statistics for the week… Study: 12 hours. Sleep: 8 hours/night; Fun: 2 days. Example fun: Our class held a Game-of-Thrones watch party. Straight-Shooter Sally: “Game of Thrones unites multiple generations under one roof. My parents love this show just as much as I do!”
No worries there. I think within 5-6 years all hospitals will be completely covered by UVC LEDs (or light fixtures having those). Bacteria and virus have not evolved to have strong defenses against that yet over the past 4.5 billion years.