Thanks to Richard for presenting the case of a middle-aged man who presented with acute onset of lower back pain, intermittent abdominal pain, and emesis, found to be septic, work up revealing Mirizzi syndrome causing acute cholangitis which led to klebsiella bacteremia and L spine osteomyelitis! Whoosh!
Klebsiella is found along the GI tract and can cause UTIs, pneumonias, osteomyelitis, GI infections, and surgical site wound infections.
Charcot triad of pain, fever, and RUQ pain is found in only ~50% of patients who present with acute cholangitis. So do not rule out the diagnosis if someone doesn’t have all three.
Mirizzi syndrome is rare and can be accompanied by acute chonagitis, acute cholecystitis, or acute pancreatitis. Management involves antibiotics to treat a concurrent infection in the biliary tree as well as surgical resection of the gallbladder and impacted stone.
Differential for hyperbilirubinemia:
Remember that the most common reasons for conjugated hyperbilirubinemia are extrahepatic causes and include the following:
Benign biliary strictures (5-30%)
Biliary stent obstruction (~20%)
Most common bacteria:
E coli (25-50%)
Charcot’s triad (~50% have all 3)
Reynold’s pentad: (rare, ~5%)
Cholestatic LFT pattern ⇒ can progress to hepatocellular LFT pattern
Assessment of disease severity
Severe (suppurative) cholangitis — Acute cholangitis is considered severe if it is associated with the onset of dysfunction in at least any one of the following organs/systems:
Elise presented a case of a middle age man with recently diagnosed pancreatic adenocarcinoma on chemo presenting with acute loose watery stools (“too many to count”) and abdominal discomfort. He appeared septic on presentation and was found to be neutropenic. Unfortunately (or fortunately) it is not the typical C.diff colitis, but actually norovirus!
Definition: defined as watery stool 3x in 24 hours, < 14 days duration
Most are infectious in etiology in an acute setting
Other causes: Ingested osmoles, malabsorption
Secretory: High volume, watery, no systemic symptoms, usually due to small intestinal involvement
Most common causes are viral (rota and noro), enterotoxin, ETEC, or vibrio chlolarae.
Infection of the bowel wall, usually the cecum but can involve ascending colon & ileum, leading to tissue necrosis
Fever, mean of 3 weeks after cytotoxic chemo
Abd pain, distension, N/V, watery/bloody diarrhea
Usually RLQ pain, can mimic appendicitis.
4th gen cephalosporins i.e. cefepime + Flagyl, surgery is generally avoid but indicated if e/o perforation
Most common viral cause of gastroenteritis worldwide, all age range affected
19-21 million cases every year in the US
Unclear reason, peak incidence during winter months.
Food born outbreaks is common: leafy greens, fruits, shell fish.
Fecal oral transmission, RNA virus
Different genotypes exist with further sub-groups, tend to have a preference for certain blood type.
Incubation: 24-48 hours, affects the small intestines
Very infectious, can cause full blown infection even if exposed to a small amount (< 100 viral particles)
Extremely stable in the environment, resists freezing or heating up to 60 degrees C, disinfection requires chlorine or EtOH
Viral shedding is max over the first 24-48 hours, and pts can continue to shed for up to weeks
Duration: 48-72 hours
Watery diarrhea, N/V, abd pain.
Vomiting usually prominent
Usually self-limiting but can be severe in immunocompromised patients
Contact plus isolation
Notify infection control (contact plus isolation)
If you have been exposed to someone with norovirus and you are symptomatic, PLEASE CALL IN SICK since this illness is highly contagious. Notify us and employee health. You have to be asymptomatic for at least 48 hours, and you have to be cleared by employee health, prior to returning to work.
Thanks to Joe for presenting the case of an elderly man with no known medical history who presented with acute AMS, found to have L facial swelling and crepitus, eventually diagnosed with necrotizing Ludwig’s angina!
Necrotizing fasciitis (NF) is a surgical diagnosis and involves infection of muscle and subcutaneous fat.
CT is a useful tool to help with diagnosis and in one case series had a 100% sensitivity and >80% specificity for diagnosing NF.
LRINEC or Laboratory Risk Indicator for NF is a lab-based risk assessment tool to help risk stratify patients with possible NF. It has a sensitivity of 80% and specificity of 67%. It should NOT supplant your clinical judgement.
Ludwig’s angina refers to any infection of the submandibular space (not just NF). Normally the treatment for Ludwig’s angina is antibiotics. In the case of NF, urgent surgical debridement is necessary. In spite of antibiotics and debridement, head and neck necrotizing infections are associated with a high mortality rate (~40%).
In patients with Ludwig’s angina, always involve anesthesia AND ENT to help secure airway. Oral intubation is associated with higher rates of laryngospasm in these patients so oftentimes nasal intubation is preferred.
Deep neck infections:
Infection of deep tissues, specifically muscle fascia and subcutaneous fat.
Two main types
Type 1: polymicrobial
More common in elderly and those with significant comorbidities including diabetes, immunocompromised states, PVD, etc.
Blood cultures are positive in ~20% of patients.
Type 2: monomicrobial (usually GAS but can be other beta-hemolytic strep and MRSA)
Can be seen in any age group and without any underlying disease.
Remember that you do not need to have a penetrating injury for NF. Oftentimes, blunt trauma is the preceding history and overlying tissue does not show any signs of infection, leading to the “pain out of proportion to exam” finding.
Systemic signs of toxicity (including hypotension and shock), rapid progression, crepitus.
LRINEC or the Laboratory Risk Indicator for NF is a lab-based risk assessment tool to help risk stratify patients with possible NF.
It has a sensitivity of 80% and specificity of 67%. It should NOT supplant your clinical judgement.
CT scan is highly sensitive (100% in one case series of 67 patients) and specific for differentiating NF from celllulitis.
Ultimately, NF is a surgical diagnosis so consult surgery early if you are concerned about the diagnosis and before waiting for imaging in an unstable patient!
Early surgical intervention and debridement
Beta lactam/beta lactamase inhibitor or carbapenem PLUS
vancomycin or other similar drug for MRSA coverage PLUS
Eagle effect: at high bacterial loads, there is reduced efficacy of beta-lactam antibiotics for strep pyogenes infections due to reduced exposure of penicillin binding protein on the bacteria. Clindamycin works better in these situations and does not rely on the penicillin binding protein site.
Toxin neutralization: clindamycin has the ability to suppress synthesis of bacterial toxins that cause systemic symptoms in patients with NF.
Other therapies such as hyperbaric oxygen and IVIG have not shown reliable evidence of benefit in studies and are not currently recommended by the IDSA.
Mortality is high even with appropriate treatment (up to 45%).
Refer to this amazing review by NEJM for more info on NF.
Today, we talked about the very interesting case of a middle-aged man who presented with acute migrating oligoarthritis, found to be febrile with an inflammatory synovial fluid and elevated ASO titers consistent with acute rheumatic fever!
Nonsuppurative manifestations of GAS infection include acute rheumatic fever (ARF), acute GN, and Scarlet fever.
Use the modified Jones Criteria to help you diagnose ARF and treat early if high suspicion for the disease (do not wait for titers to come back).
Late complications of ARF include rheumatic heart disease (10-20 years after infection) and Jaccoud arthropathy.
Treatment of ARF involves NSAIDs for arthritis, PCN G IM x 1 dose for acute presentation and then monthly for prophylaxis, and patient education about oral hygiene to prevent endocarditis and need for prophylaxis before invasive procedures.
Differential diagnosis for a migratory arthritis
Vasculitis (IgA, cryo, ANCA associated)
Bacteremia (staph, strep, mening/gonococcal)
Pulmonary infections (mycoplasma, histoplasma)
Nonsuppurative complications of GAS infection
Nonsuppurative sequela that occurs 2-4 weeks after GAS pharyngitis
More common in children 5-15 years of age
More common in resource limited settings
Poorly understood, ?molecular mimicry
Two primary manifestations of disease
(Table above from UpToDate)
Rheumatic heart disease (10-20 years after infection), primary involves the mitral valve >aortic valve.
Leading cause of cardiovascular death in the first 5 decades of life in resource limited settings
Revised Jones criteria (joint and cardiac manifestations can only be counted once).
Carditis and valvulitis (clinical or subclinical) – 50-70%
Usually pancarditis. Valvulitis especially of mitral and aortic valves, shown as regurg on echo.
Carey Coombs murmur: short mid-diastolic murmur heard loudest at the apex
Arthritis (migratory, involving large joints) – 35-66%, earliest symptom
Several joints affected in quick succession, each inflamed for a day or two to one week. Most common are knees, ankles, elbows, and wrists.
CNS involvement (Sydenham chorea) – 10-30%
Subcutaneous nodules – 0-10%
Erythema marginatum – <6%
Elevated acute phase reactants (ESR, CRP)
Prolonged PR interval on EKG
Diagnosis requires evidence of prior GAS infection plus:
2 major OR
1 major + 2 minor criteria OR
3 minor criteria (only if patient has history of prior episode of ARF)
In a high prevalence setting, slightly modified criteria are used.
Prior GAS infection through either
Positive rapid strep antigen test
Elevated or rising ASO titers
Symptomatic relief of acute disease manifestations
Carditis: if severe, heart failure treatments
Eradication of GAS
IM PCN G benzathine x 1
Contacts (throat culture test and treat if positive)
Ppx against future GAS infection to prevent progression of cardiac disease
PCN G IM once a month
For 5 years or until 21 years of age (whichever is longer)
If ARF with carditis and residual heart disease
10 years or until 40 years, sometimes even lifelong
Thanks to Katie for presenting the interesting case of a young man with history of disseminated TB with TB meningitis and hydrocephalus requiring VP shunts, admitted for acute LUE weakness, L homonymous hemianopsia, and memory impairment, found to have acute strokes in multiple vascular territories due to TB related CNS vasculitis!
Remember that arterial dissection is the most common cause of stroke in a young patient.
CNS vasculitis can be primary or secondary to a systemic illness. It typically presents with infarcts in multiple vascular territories. Treatment involves immunosuppression with high dose steroids + cytoxan/rituxan.
CNS vasculitis is the most common cause of severe neurologic deficit in patients with TB meningitis.
Vasculitis in CNS TB is the result of a hypersensitivity reaction to proteins released from the bacteria.
TB meningitis requires an extended course of anti-TB treatment, generally up to 1 year or more. Serial LPs are obtained to monitor adequate response to therapy.
Etiologies of stroke in a young adult
Coagulopathy (think of conditions that cause both arterial and venous thrombosis)
Leukostasis in setting of leukemia
Myeloproliferative disorders (PV, ET, CML)
Paroxysmal nocturnal hemoglobinuria
Dissection (most common cause of stroke in a young person)
Malformations (AVMs, aneurysms, moyamoya)
Cerebral venous sinus thrombosis
Large vessel: Takayasu, GCS
Small to medium: Kawasaki, PAN, ANCA-associated
Fungi (esp cocci)
Collagen vascular disease (i.e. lupus)
CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)
Organic acid disorders
Cocaine and meth
Rheumatic valve disease
Mitral valve prolapse
Endocarditis with septic emboli
Three main manifestations:
TB meningitis (most common presentation in low incidence settings like the US)
Spinal tuberculous arachnoiditis
Spillage of tubercular protein into the subarachnoid space results in an intense hypersensitivity reaction and inflammation resulting in
Proliferative arachnoiditis (fibrous mass encasing cranial nerves and vessels adjacent to it)
Vasculitis with resultant aneurysm, thrombosis, and infarction
1% of all TB cases, 5% of all extrapulmonary TB cases
Meningitic phase: meningismus, headache, vomiting, lethargy, confusion, CNS signs, some motor deficits
Paralytic phase: stupor, coma, seizures, hemiparesis (death within 5-8 weeks)
Characteristic CSF findings of low glucose, elevated protein, lymphocytic pleocytosis
CSF AFB smear and culture: in general, a minimum of 3 serial LPs should be performed, as diagnostic yield increases f
Nucleic acid tests: Xpert MTB/RIF assay should be submitted in the setting of high clinical suspicion and negative AFB staining.
Intensive phase (2 months): four drugs RIPE. Ethambutol has poor CNS penetration so some use fluoroquinolones instead.
Continuation phase (7-10 months)
A review of 9 trials on 1337 patients found that use of steroids reduced death and disability by ~25%.
Benefit higher if started earlier in disease process.
Treat for 8 weeks, slow taper.
A retrospective study in Stroke 2018 on patients with TB meningitis found that those >40, with concurrent HTN, dysplipidemia, and DM were more likely to have this complication. Some small case series showing benefit in reducing future strokes with the use of Aspirin.
Thanks to Tim for presenting the interesting case of a middle-aged man with h/o inadequately treated syphilis who presented with neck stiffness worse in the mornings, back pain, and blurry vision, admitted for presumed neurosyphilis. Exam revealed inflammation of T2/T3 joints, L SI joint tenderness, and an inflamed R foot with dactylitis of the 3rd and 4th digits. Further history revealed a recent gonorrhea/chlamydia for which he was treated and HLA B27 positivity consistent with reactive arthritis! He was started on NSAIDs with significant improvement of symptoms.
Neurosyphilis is most commonly seen in HIV positive patients and can present at any time after infection.
Early neurosyphilis occurs within the first year after infection and involves the CNS, meninges, and vasculature
Neurosyphilis presents with posterior uveitis or pan-uveitis whereas reactive arthritis presents with anterior uveitis
Late neurosyphilis occurs >10 years after infection and involves the brain and spinal cord parenchyma
The four main spondyloarthropathies are ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and IBD-related arthritis.
The genital pathogen most commonly associated with reactive arthritis is chlamydia trachomatis.
Our doctor-in-training Jacqueline presented a middle man with infrequent medical care, with a history of heavy alcohol use, who presents with generalized swelling and anorexia. He was septic on presentation with a distended abdomen. Ascitic fluid anlysis was concerning for bacterial peritonitis, and blood cultures (4/4 bottles) were positive for acinetobacter with OXA resistance marker!
Spontaneous bacterial peritonitis
Important to distinguish between Spontaneous bacterial peritonitis (SBP) vs Secondary bacterial peritonitis (also SBP but for the sake of clarity, SBP from this point on will refer to spontaneous bacterial peritonitis)
Secondary: Bacterial peritonitis secondary to something else besides spontaneous, i.e. bowel perforation, surgery.
100% mortality without surgical intervention. Surgical risk is high but patient mortality is almost guaranteed without surgery!
If Spontaneous BP, mortality can approach 80% with abdominal surgery.
Diagnosis: history, fluid analysis
Cultures from peritoneal fluid usually polymicrobial (gut flora)
Tertiary bacterial peritonitis: Persistence of peritonitis or abscess following adequate treatment of primary or secondary peritonitis
Pts with cirrhotic ascites, suspect SBP in all these patients, and also pts with ascites suffering from a GIB.
Organisms: E.coli, Klebsiella, strep pneumo are most common, usually single organism
Less common: Acinetobacter, pseudomonas, proteus
If polymicrobial of anaerobes, suspect secondary bacterial peritonitis
Rarely fungal but they have been described, poor prognosis.
S/S of ascites
May have fever, malaise, encephalopathy, decompensated liver cirrhosis, peritoneal signs sometimes.
Frequently an instigator for hepatorenal syndrome in cirrhotic patients.
PMN > 250 cells/mL
Absence of secondary causes
Cefotaxime 2g Q8H
Ceftriaxone once daily is an alterative with some evidence trending toward improved survival and less ICU stay with 2g daily dosing vs 1g.
Cefepime 1-2g Q8H is an alternative as well esp for resistant pathogens.
Fluoroquinolones: Consider alternative if pt already on a quinolone for prophylaxis prior to developing SBP. Can use Cipro, Levo, or Moxi.
Beta lactam/Beta lactamase inhibitors i.e. Zosyn
Duration: At least 5 days
Albumin: Recommended, RCT published in NEJM in 1999 established the administration of albumin decreases the incidence of renal failure with albumin + antibiotics as well as decrease in mortality.
Patients in the study who were most likely to benefit from albumin had:
Bili > 4
Cr > 1
BUN > 30
1.5g albumin /kg on day 1, the 1.0g/kg on day 3. Dose limited to max of 100g
HRS (Hepatorenal syndrome): 1.0g/kg albumin days 1 & 2 and see if renal function improves (albumin challenge)
Renal failure can be seen in 30-40% of patients with SBP
Prognosis tends to be poor once HRS sets in
Type 1: Rapid progressive decline, 50% 1 month mortality
Type 2: More subacute/chronic, not associated with an inciting event, median survival 6 months
Cirrhotics presenting with GIB should get primary prophylaxis, total duration of therapy x 7 days
Ascitic protein < 1.0 g/dL can also be considered (RCT published in Journal of Hepatology in 2008)
Ascitic protein <1 and Childs Pugh > 9 or T.bili > 3 or renal dysfunction: can also consider long-term primary prophylaxis, based on an RCT from Gastroenterology in 2007, drug of study was norfloxacin.
Indicated after first episode of SBP, one year recurrence rate of 40-70%, mortality rate of 50-70%
Meds: Norfloxacin or cipro daily, Bactrim also an equivocal alternative
Certain strains can survive in a desiccated environment for weeks.
Most commonly in ventilator associated pneumonia and blood stream infection (1.5% – 2.4%)
Others: Central line, catheters, surgical site infection
Can be contamination, pts and health care workers can be colonized
Can also present as endocarditis or meningitis or ocular infection (contact lens)
Peritonitis secondary to acinetobacter usually more common in peritoneal dialysis patients.
Prior antibiotics, especially beta lactams, carbapenems, fluoroquinolones
Presence of catheters, ICU
PD (especially in setting of peritonitis secondary to actinobacteria)
Trauma, burn, immunosuppression
Increasingly resistant, both acquired and inherent
ESBL phenotype also emerging
1st line: cephalosporin (ceftaz, cefepime), beta-lactam/beta lactamase inhibitor, carbapenems are highly effective, ampicillin0sulbactam is also very effective.
Sometimes combination therapy is used i.e. with a fluoroquinolone or aminoglycoside due to concerns of emerging and acquired resistance but limited data on combo therapy vs emergences of resistance or whether clinical outcome is improved.
Other possible options: minocycline, tigecycline, polymyxins
2x more likely to die from a carbapenem resistant strain