Case 9: Bacteraemic infection with an intra-abdominal focus Clinical outline 92 yr old man Presented with RUQ pain and

vomiting (x5) over one day. Pain was severe, radiating across abdomen to LUQ. Gave history of episodic yellowing for many years. Acute dyspnoea developed while in ED: nebulisers given Past history includes CVA, LVF (moderate), CAL, AAA repair 1979. Medications: verapamil, diuretic, inhalers. O/E: unwell, having rigors, mild jaundice, alert HR 120/m regular, 140/80, Temp 38 O2sat 94% on 24% mask Soft BS bilaterally; prolonged exp wheeze, some bi-basal creps Soft abdomen, distended +, tender over RUQ . No stigmata of liver disease. No splenomegaly.

What is your provisional diagnosis and differential? Pause to think and compose your own answer before proceeding.

Differential diagnosis 1. Ascending cholangitis with bacteraemia; probable gall stone in the common bile duct The most likely diagnosis . This patient displays the syndrome called Charcots Triad. 2. Acute cholecystitis 3. Alcoholic hepatitis: the degree of pain is out of keeping with this diagnosis. Rigors implies secondary infection. Tenderness consistent. 4. Early RLZ pneumococcal pneumonia : may present with an acute abdomen, usually with UQ pain, usually pleuritic. Jaundice not infrequently occurs in pneumococcal pneumonia. Pneumonia may not be clinically apparent at presentation. Absence of cough unusual. In all likelihood decompensation of LVF and CAL probably responsible for dyspnoea. Absence of signs of peritonism make perforation less likely though not impossible in an elderly person.

What investigations would be useful to confirm your clinical suspicions?

Initial investigation results Hb 142g/l WCC 13.6 Plt 127 Film comment: Left shift with mild toxic changes. Mild macrocytosis (102fL). Consistent with liver disease. bilirubin 69 GGT 223 Alk phos 185 ALT 294 AST 317

Blood cultures taken: Gram negative rods isolated after 2 hrs of incubation CXR : increase interstitial markings c/w LVF Abdominal U/S arranged: CBD 9mm in diameter (was 5mm on previous u/s in May 1998). No gall stones seen.

What is your interpretation of these results?

Interpretation of initial results The patient has moderately deranged LFTs with a mixed picture c/w cholangitis Blood cultures confirm bacteraemia; there is a high incidence of bacteraemia in cholangitis The ultrasound is very suggestive of CBD obstruction with diameter of CBD at the upper limit of normal. CBD stones may easily be missed on u/s.

What are the management principles for this condition? Management principles 1. EMPIRIC antibiotic therapy: Patient given gentamicin and ticarcillin/clavualate (Timentin). More usual protocol is ampicillin/gentamicin with metronidazole (see Antibiotic guidelines). Principle is to cover aerobic gram negatives and enteric streptococci (S. milleri group and others) well. Anaerobic cover also important particularly in patients with malignant biliary obstruction. Usual protocol also covers enterococci which may also contribute though these are seldom the major pathogens and antibiotics such as timentin that do not cover enterococci usually work. Temperature, pain and rigors settled over next 48 hrs. Have a look at the relevant section of the antibiotic guidelines for cholangitis. Are there particular problems with giving gentamicin in the presence of liver disease or jaundice?

1. Early ERCP to relieve CBD obstruction: Relief of obstruction is as crucial as providing antibiotic therapy. Patient underwent ERCP on day 2; the ampulla of vater was inflamed and after cholangiogram, spincterotomy was performed. A small gall stone liberated together with dirty-looking bile. A gastric ulcer, possibly malignant was also found and biopsied. 2. Supportive care: judicious hydration, monitor observations closely etc 3. Modify antibiotic therapy in the light of susceptibility of cultures: = DIRECTED THERAPY Culture from blood identified as E. coli resistant to ampicillin, timentin, cefotaxime and sensitive to gentamicin, ciprofloxacin, imipenem. Patient was changed to oral ciprofloxacin 500mg bd and did well. Note that gentamicin not advisable beyond a few doses in elderly patients and does not penetrate well into bile. However it has a good initial impact on the bacteraemic component of this disease which is most important. Ciprofloxacin was the only oral choice available based on susceptibilities. However some elderly can develop an acute confusional state or tremor while on ciprofloxacin, especially at higher doses, so beware. This bacterial isolate is probably making an extended spectrum -lactamase (ESBL) enzyme that is able to destroy ampicillin and third generation cephalosporins. Whilst this enzyme is inhibited by the clavulanate in timentin, this bacteria is probably producing enough -lactamase to overcome the effect of clavulanate. Only relatively simple mutations in the usual plasmid-mediated -lactamase (penicillinase responsible for ampicillin resistance) of E. coli is required to extend its spectrum to include cefotaxime. Further reading Antibiotic guidelines 13th Edition