A 50-year-old man presents to hospital with fever and an acute abdomen. He undergoes an emergency laparotomy, the findings of which include perforated carcinoma in the splenic
flexure and generalized faecal soiling of the peritoneum. He undergoes a left hemicolectomy with a defunctioning colostomy. Post-operatively he is transferred to the intensive care unit because of septic shock.

a) What antibiotic regimen will you consider and why?

Despite a five-day course of antibiotics he remains unwell with fever up to 38.50C, WCC 16.7 x 109 /l. He is unable to tolerate oral feeds and is on TPN.

b) List the likely abdominal causes of persistent fever and leukocytosis?

Blood cultures show Candida glabrata in one of the three bottles.

c) List 4 predisposing factors for this infection in this patient.

d) What antibiotic therapy will you commence whilst waiting for sensitivities and why?

e) Based on the culture report, give one other investigation, the results of which might influence the prognosis and duration of antifungal treatment, and the rationale for your choice.

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College Answer

a) What antibiotic regimen will you consider and why?

  • Triple therapy or Timentin or Tazocin – cover enterococcus, gram negatives and anaerobes.
  • May consider adding empiric fluconazole
  • Vancomycin, gentamicin, metronidazole if penicillin allergic

Despite a five-day course of antibiotics he remains unwell with fever up to 38.50C, WCC 16.7 x 109 /l.

He is unable to tolerate oral feeds and is on TPN.


b) List the likely abdominal causes of persistent fever and leukocytosis?

  • Intra-abdominal collection
  • Wound infection
  • Acalculous cholecystitis
  • Pancreatitis
  • Stomal necrosis


Blood cultures show Candida glabrata in one of the three bottles.
c) List 4 predisposing factors for this infection in this patient.

  • Malignancy
  • Abdominal soiling
  • TPN
  • Recent broad spectrum antibiotic therapy
  • Indwelling CVC

d) What antibiotic therapy will you commence whilst waiting for sensitivities and why?

  • Voriconazole or amphotericin B or caspafungin
  • Candida glabrata may not be sensitive to fluconazole


e) Based on the culture report, give one other investigation, the results of which might influence the prognosis and duration of antifungal treatment, and the rationale for your choice.

  • Echocardiography – vegetations
  • CT / USS abdomen – liver abscess
  • Ophthalmic examination – retinal abscesses

Discussion

This question refers to the management of faecal peritonitis.

 The first part asks for empirical antibiotic therapy in abdominal sepsis. The "triple therapy" this refers to is the well known ampicillin-gentamicin-metronidazole combination. There is reference to the fact that single broad agent therapy may be equivalent in its efficacy to the standard multidrug regimen. As a single agent, Tazocin (piperacillin/tazobactam) is a fine choice. Perhaps it will not cover some of the more resistant enterococci, but their low pathogenicity makes it unlikely that they will pose a problem. And it will certainly wipe the floor with most of the gram-negatives.

The second part asks for the potential causes of fever in the feed-intolerant post-laparotomy patient. Acalculous cholecystitis and pancreatitis should be mentioned. Stomal necrosis is another possibility.

The presence of Candida glabrata in the blood cultures is explored; the candidate is invited to produce a list of factors which predispose post-operative patients to such an infection. A good article on this exact subject is available. It had found that non-albicans candidaemia is associated with CVCs and multiple antibiotic therapy. TPN also seems to all but triple the risk of non-albicans candidaemia. There is also an association with malignancy, which is biased by the fact that most studies of candidaemia have been performed in solid or hematological cancer patients. The college answer doesnt mention renal failure (because the scenario patient does not have it), but this is another significant risk factor.

Thus, in summary, risk factors for non-albicans candidaemia are as follows:

  • Repeated abdominal surgeries
  • Exposure to broad-spectrum antibiotics
  • Exposure to fluconazole
  • Diabetes
  • CVC insertion
  • TPN use
  • Malignancy
  • Renal failure

One ought to also mention that specifically the use of fluconazole may select for a fluconazole-resistant species such as C.glabrata. The next question asks which agent is the most appropriate empirical therapy for this yeast, and voriconazole or liposomal amphotericin are valid answers.

The last question asks the candidate to think about the complications of candidaemia.

One can list a few:

  • Candida endopthalimitis/retinitis
  • Candia endocarditis
  • Hepatosplenic abscesses
  • Pulmonary cavitating lesions
  • CNS involvement (meningitis or abscesses)
  • Candida arthritis

Candida endocarditis is the most feared complication, and it seems that the most common pathogen (28%) is a non-albicans species.

Candida endophthalmitis (specifically, retinitis) occurs via haematogenous seeding, and is enough of a problem for the Infectious Diseases Society of America to issue recommendations regarding early retinal examination for these patients.

The whole business of scanning the abdomen for collections is laudable, but I am not sure why the college has latched on to the idea of looking specifically for hepatic abscesses. This seems more a feature of liver transplant recipients.

References

References

Harris, Anthony D., et al. "Risk factors for nosocomial candiduria due to Candida glabrata and Candida albicans." Clinical infectious diseases 29.4 (1999): 926-928.

Lee, Ingi, et al. "Risk factors for fluconazole-resistant Candida glabrata bloodstream infections." Archives of internal medicine 169.4 (2009): 379-383.

D M Mosdell, D M Morris, A Voltura, D E Pitcher, M W Twiest, R L Milne, B G Miscall, and D E Fry Antibiotic treatment for surgical peritonitis. Ann Surg. 1991 November; 214(5): 543–549.

Chow, Jennifer K., et al. "Factors associated with candidemia caused by non-albicans Candida species versus Candida albicans in the intensive care unit."Clinical infectious diseases 46.8 (2008): 1206-1213.

Chow JK, Golan Y, Ruthazer R, Karchmer AW, Carmeli Y, Lichtenberg DA, Chawla V, Young JA, Hadley S.Risk factors for albicans and non-albicans candidemia in the intensive care unit.Crit Care Med. 2008 Jul;36(7):1993-8.

Blumberg HM, Jarvis WR, Soucie JM, Edwards JE, Patterson JE, Pfaller MA, Rangel-Frausto MS, Rinaldi MG, Saiman L, Wiblin RT, Wenzel RP; National Epidemiology of Mycoses Survey(NEMIS) Study Group. Risk factors for candidal bloodstream infections in surgical intensive care unit patients: the NEMIS prospective multicenter study. The National Epidemiology of Mycosis Survey. Clin Infect Dis. 2001 Jul 15;33(2):177-86. Epub 2001 Jun 20.

Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, Filler SG, Fisher JF, Kullberg BJ, Ostrosky-Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel JD; Infectious Diseases Society of America.Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009 Mar 1;48(5):503-35. doi: 10.1086/596757.