Gram Negative Rod Septicaemia

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Gram negative bacillary septicaemia is a relatively uncommon finding in palliative medicine as deteriorating patients who develop sepsis are often treated conservatively with comfort care and investigations such as blood culture would be inappropriate in this context. However in patients who are not thought to be in their last few weeks of life, when there is a sudden deterioration potentially due to sepsis, blood cultures along with treatment with broad-spectrum antibiotics might be appropriate, and in these cases there will be occasions where blood cultures grow a gram negative rod.

Underlying aetiology, epidemiology and organisms

Aetiology and Risk Factors

In the palliative medicine context, gram negative septicaemia is most likely to occur in the following situations:

  • Urosepsis, especially in patients who have bladder or prostate pathology (e.g. transitional cell cancer of the bladder) or a ureteric stent (e.g. from previous malignant obstruction)
  • Peritonitis or an intra-abdominal collection in the context of a malignancy invading into the bowel wall (e.g. colorectal cancer)
  • Biliary sepsis in the context of a malignancy obstructing the biliary tract (e.g. cholangiocarcinoma)
  • Spontaneous bacterial peritonitis, especially in the context of patients with cirrhosis

Additional risk factors for gram negative sepsis include:

  • Immunosuppressive treatments (e.g. steroids)
  • Liver failure
  • Poor nutritional status
  • Hypoalbuminaemia
  • Pulmonary disease
  • Central venous catheter in situ

Organisms

Some of the more common organisms causing gram negative septicaemia are:

Antibiotic Resistance

There is increasing rates of antibiotic resistance so that traditionally standard antibiotics are having less effect. Resistance patterns varies geographically. Some figures from a large study from the United States showed the following resistance rates:

Organisms Fluoroquinolone resistance Third and fourth generation cephalosporin resistance Carbapenem resistance
E. coli 40% 20%
P. aeruginosa 30% 25% 25%
K. pneumoniae 30%
Enterobacter 40%

Some gram negative organisms, primarily K. pneumoniae but also a small proportion of E. coli, have extended-spectrum beta lactamases (ESBL) which gives resistance against beta-lactams. These bacteria often are also resistant to multiple other antibiotics too.

Clinical Presentation and Complications

Most patients feel unwell and are found to have a fever. Confusion and drowsiness is also common.

Additionally there are often symptoms and signs of the site of primary infection (e.g. flank pain and dysuria in the case of pyelonephritis).

Hypotension (septic shock) is common, occurring in about one-quarter patients with gram negative septicaemia. Disseminated intravascular coagulation may also complicate gram negative sepsis and this may manifest with bruising and petechiae.

Investigations and Diagnosis

Gram negative septicaemia is diagnosed on blood cultures. Identification of the specific organism and sensitivities often is delayed by a day or two from the initial diagnosis.

Other tests that may be helpful include:

  • C-reactive protein - This will be elevated and will drop with effective therapy. Usually the drop in CRP lags one or two days behind treatment.
  • Full blood count - A low platelet count may be suggestive of DI
  • Creatinine - Acute kidney injury is common
  • Billirubin and liver enzymes - elevation of bilirubin, GGT and ALP may suggest biliary sepsis, especially in the context of right upper quadrant pain (Charcot's triad)
  • Urine microscopy and cultures are useful if urosepsis is thought to be a possible source of the infection.

Imaging to look for the potential source may also be helpful. If biliary sepsis is suspected liver and biliary tract ultrasound may confirm biliary obstruction. If an intra-abdominal collection is possible, an abdominal and pelvic CT scan may be useful. If spontaneous bacterial peritonitis is suspected, a diagnostic ascitic tap testing for white cell count and differential and culture will be useful to confirm the diagnosis and guide treatment.

Management

The appropriate treatment of Gram negative sepsis, like any acute medical problem in palliative medicine, will depend a lot on the prognosis of the underlying palliative illness, the patient's usual functional state, and patient and family wishes. In some cases a comfort care based approach to treatment will be most appropriate; in others basic ward treatment with IV antibiotics and IV fluids will be reasonable. Usually escalation of treatment (e.g. management with inotropic support for septic shock in intensive care) is not appropriate in palliative care patients although there will be the occasional time this might be considered.

Empirical antibiotic therapy

The appropriate antibiotic therapy will vary depending on which region of the world the patient lives in and local guidelines should be considered. For immunocompetent patients often a good choice will be piperacillin/tazobactam, e.g.

Tazosin 4.5 g three times a day IV 

For immunocompromised patients (e.g. neutropaenic) broad spectrum dual antibiotic therapy is usually recommended, for example:

Gentamicin 5mg/kg IV daily
AND One of the following
 An anti-pseudomonal cephalosporin (e.g. ceftazadime 2 g three times a day IV)
 OR
 Piperacillin/tazobactam (e.g. Tazocin 4.5 g three times a day IV) OR a carbapenem (e.g. meropenem 1 g three times a day IV) 

For patients with severe penicillin allergies a fluoroquinolone may be a good alternative (e.g. ciprofloxacin 400 mg twice daily IV).

Once organism identification and sensitivities are available, antibiotics can be modified as appropriate.

Duration of therapy

There are no randomized controlled trials suggesting the best length of course of therapy. A good rule of thumb is to continue IV antibiotics until there has been at least 48 hours without a fever and the patient is starting to look better. Conversion to an oral antibiotic at this stage is probably appropriate.

Catheter removal

If a central line catheter is in situ and is thought to be the source of the infection, then this should be removed.

Prognosis

The prognosis depends quite a lot on the underlying palliative illness.

Specific negative prognostic indicators also include:

  • Septic shock
  • ARDS
  • DIC
  • Anuria
  • Unknown origin of infection

Authors

Graham Llewellyn Grove