Microbiology Nuts & Bolts
  • Home
  • Basic Concepts
    • What is infection?
    • Normal flora
    • Diagnosing infection
  • Microbiology
    • Basic bacterial identification
    • Interpreting bacteriology results
    • Interpreting serology results
  • Infection Control
    • What is infection control?
    • Universal precautions
    • MRSA
    • Clostridium difficile
  • Clinical Scenarios
    • Respiratory infections
    • Urinary infections
    • GI infections >
      • D&V
      • CDAD
    • CNS infections
    • Skin & bone infections
    • Sepsis
  • Antibiotics
    • Antimicrobial Stewardship
    • How antibiotics work
    • How to choose an antibiotic?
    • Reviewing antibiotics
    • Antibiotic resistance
    • Testing antibiotic resistance
    • Penicillin allergy
    • Theraputic Drug Monitoring
  • Guidelines
  • Lectures & Lecture Notes
    • Medical Students
    • Curriculum for the Foundation Program
    • Foundation Year 1
    • Foundation Year 2
    • Other Lectures
  • The Bug Blog
  • Buy the book...
  • NEW Edition Updates
  • Peer Reviews
  • Our Facebook page
  • Want to know more?
  • Contact

No, no, no, … oh no… Nocardia!

11/10/2018

 
Looking down the blood cultures list whilst prioritising what needed phoning out first the Microbiologist noticed a blood culture positive on day 3 with a Gram-positive bacillus in the aerobic bottle only. Normally this wouldn’t provoke much interest as most pathogens grow within 12-24 hours and most Gram-positive bacilli are skin contaminants (Corynebacterium spp. and Cutibacterium spp.). However these were unlikely in this case: Corynebacterium spp. normally grow faster than this and would be in both bottles whereas Cutibacterium spp. although anaerobes tend to grow much slower. The clinical details just said “fever” (not overly helpful!) and considering the sample was 3 days old already, it didn’t seem that urgent, so the Microbiologist put it to the bottom of the list and got on busily calling out all of the Gram-negative bacilli and Gram-positive cocci, as these were more likely to be significant.
Picture
​Having cleared all the other positive blood cultures the Microbiologist came back to the Gram-positive bacillus. Looking up where the patient had been on this admission showed the blood culture had been taken in the Emergency Department, the patient had then briefly gone to the medical admissions unit before being discharged later the same day. Not much to go on there then. Maybe it wasn’t going to be significant after all.
 
Out of curiosity the Microbiologist then decided to check if the patient had been in before. This threw up something unexpected. The patient had had multiple attendances to the haematology ward as well as the outpatient clinic. Pulling up the clinic letters showed that the patient actually had chronic lymphoblastic leukaemia (CLL) and would therefore be immunosuppressed. This changed the situation; the blood culture could be an opportunistic pathogen and not a contaminant at all, muttering to himself, “chronic lymphoblastic anaemia is significant info for the specimen request card, when will they learn!” the Microbiologist decided to phone out the result straight away.
 
Still cursing healthcare staff who don’t fill out request forms with adequate clinical details, the Microbiologist bleeped the Haematology Registrar to find out more…
 
It turned out that the patient had presented to the Emergency Department with a fever and shortness of breath. The fever settled and the blood tests showed the patient wasn’t neutropaenic. The blood cultures had been taken before the blood test results came back. A dose of Piptazobactam had also been given in case the patient had febrile neutropaenia but this had been stopped when the neutrophil count was shown to be in the normal range. “As the patient was feeling better they were allowed to go home”, the Registrar said a little sheepishly knowing something was amiss if the Microbiologist was “showing concern”.
 
“Mmmmm…” said the Microbiologist to himself, “a blood culture positive on day 3 with a Gram-positive bacillus in the aerobic bottle only”… “Mmmmm…” he said again “this could be Nocardia”. The Microbiologist suggested getting the patient back in for a review whilst the laboratory tried to identify the microorganism. By the time the patient had been reassessed the organism had a name, Nocardia farcinica.
Nocardia farcinica
Nocardia farcinica
​What are the Nocardia spp.?
Nocardia spp. are a group of aerobic Gram-positive bacilli which do not take up Gram’s stain very well and so appear as long beaded Gram-positive bacilli. They have some mycolic acid in their cell wall, as a result they can be stained using a modified Ziehl-Neelsen (ZN) stain. The modified ZN stain uses 0.5-1% acid-alcohol as a decolouriser rather than the normal 3% used for Mycobacterium spp.  
 
Nocardia spp. live ubiquitously in soil, water and organic material within the environment. They are found worldwide.
 
On culture Nocardia spp. are slow growing, taking 2-3 days to produce typical colonies which look a bit like small fungi with hyphae. In fact early Microbiologists thought they were fungi and hence named all of the similar organisms to Nocardia spp. the Actinomycetes (a mycete is a fungus). They are bacteria though.
 
There are over 80 species within the Nocardia genus but the most common causing human disease include:
  • Nocardia asteroides
  • Nocardia farcinica
  • Nocardia nova
  • Nocardia camea
  • Nocardia braziliensis
  • Nocardia otitidiscaviarum
  • Nocardia cyriacigeorgica
  • Nocardia abscessus
 
How does infection with Nocardia spp. present?
The most common presentation of infection with Nocardia spp., known as nocardiosis, is with pneumonia, lung abscesses and lung cavitation. This is because the bacteria are most commonly acquired by inhalation. People with a normal immune system usually clear the bacteria but immunosuppression, especially defective cell mediated immunity, predisposes to this opportunistic pathogen. The most common immune problems include prolonged steroid use, haematological cancer, chemotherapy, organ transplantation and Human Immunodeficiency Virus infection.
 
Occasional infections occur in skin and soft tissue following contamination of wounds e.g. soil inoculation of a thorn injury or an animal or insect bite. In this case cellulitis or superficial abscesses are the most common presentations.
 
With pulmonary infections, infection spreads from the lungs via the blood stream to any body organ, but especially the brain where the bacteria cause abscesses; this is more common with N. farcinica than other species. Untreated pulmonary infections sometimes erode through the tissues of the thorax to discharge onto the chest wall through sinuses.
Nocardia farcinica chest xray
Click for larger image
How is nocardiosis diagnosed?
Nocardiosis is diagnosed through the culture of Nocardia spp. from normally sterile sites. Identification of the bacterium used to be a bit of a nightmare and was based upon colonial appearance on agar, Gram appearance, modified ZN and unreliable biochemical methods. Nowadays MaldiTOF and PCR are excellent and reliable ways of identifying this bacterium.
 
If someone is suspected of having nocardiosis then further imaging is required, especially of the thorax. It is worth talking directly to the Radiologists to find the best modality for investigating. In my experience CT is often useful but I’m not a Radiologist. Confirmation of infection usually requires sticking a needle into the suspected site and aspirating pus for further laboratory testing; again this is often conducted by Radiologists.
 
Any immunocompromised patient with cutaneous or pulmonary infection should also have a brain scan to look for dissemination.
 
How is nocardiosis treated?
The treatment of nocardiosis can be difficult. It is important to test the individual bacteria for antimicrobial sensitivity as they are not always predictable. There is no national or international standard method for doing this but both Etests and broth dilution are suitable.
 
The species of bacterium is also important as some are more resistant than others e.g. N. farcinica is usually resistant to 3rd generation cephalosporins such as Ceftriaxone as well as Imipenem. Source control is also important, including drainage of abscesses and debridement of infected tissue wherever possible.
 
Trimethoprim-Sulfamethoxazole (Septrin) is the usual first line treatment with other agents added as required. Empirical first line treatments include:
Mild/moderate pulmonary infection
PO Trimethoprim-Sulfamethoxazole 5mg/kg BD (TDS if immunocompromised)
Severe pulmonary or disseminated infection (initial treatment)
IV Trimethoprim-Sulfamethoxazole 5mg/kg TDS
PLUS
IV Amikacin 7.5mg/kg BD
PLUS
IV Imipenem 500mg QDS
Cutaneous infection
PO Trimethoprim-Sulfamethoxazole 5mg/kg BD
Follow-on oral treatment
Severe pulmonary or disseminated infection
2 of the following:
PO Trimethoprim-Sulfamethoxazole 5mg/kg BD
PO Minocycline 100mg BD
PO Co-amoxiclav 875mg BD (note this is an unusual dose)
Duration:
  • Pulmonary 6-12 months
  • Immunocompromised or disseminated ≥ 12 months
  • For severe infection or disseminated disease IV antimicrobials should be continued for at least 6 weeks at which stage the patient can be converted to orals
  • Cutaneous 3-6 months
 
Once sensitivities are known patients on three agent regimens can be converted to two agent regimens.
 
If there is no improvement within 2 weeks of starting treatment then the patient should be reviewed, further source control undertaken and consideration given to changing the antibiotics to alternative agents. Other antibiotics shown to have activity against some Nocardia spp. include: Co-amoxiclav, Ceftriaxone, Ciprofloxacin, Clarithromycin, Linezolid, Minocycline, Doxycycline and Tobramycin.
 
Monitoring
It is important to keep a close eye on these patients to look for disease progression as well as treatment toxicity. The most important toxicity is bone marrow suppression from the prolonged Trimethoprim-Sulfamethoxazole treatment. At least fortnightly full blood count, Urea and electrolytes and liver function tests should be checked. In addition further imaging is often required; some experts repeat imaging at 1, 3, 6 and 12 months of treatment and then 6 and 12 months after treatment to ensure there is no relapse.
 
With early diagnosis and targeted antimicrobial treatment the long term survival is 90%.
 
So our patient was brought back into hospital and reassessed. A CT scan of their chest showed a number of cavities however the scan of their head was normal. They were started on IV antimicrobials and by two weeks had started to improve. The patient was advised it was going to be a long course of treatment, the Microbiologist returned to the list of blood cultures to see if he could “intervene”, or more accurately “meddle”, with any other patient and their unsuspecting Registrar!

Comments are closed.

    RSS Feed

    Blog Author:

    David Garner
    Consultant Microbiologist
    Surrey, UK

    Please DO NOT advertise products and conferences on our website or blog

    Categories

    All
    Antibiotic Resistance
    Antibiotics
    Basic Concepts
    Clinical Scenarios
    Guidelines
    Infection Control
    In The News
    Microbiology

    Archives

    October 2020
    September 2020
    August 2020
    July 2020
    June 2020
    May 2020
    April 2020
    March 2020
    February 2020
    January 2020
    December 2019
    November 2019
    October 2019
    September 2019
    August 2019
    July 2019
    June 2019
    May 2019
    April 2019
    March 2019
    February 2019
    January 2019
    December 2018
    November 2018
    October 2018
    September 2018
    August 2018
    July 2018
    June 2018
    May 2018
    April 2018
    March 2018
    February 2018
    January 2018
    December 2017
    November 2017
    October 2017
    September 2017
    August 2017
    July 2017
    June 2017
    May 2017
    March 2017
    February 2017
    January 2017
    December 2016
    November 2016
    October 2016
    September 2016
    August 2016
    July 2016
    June 2016
    May 2016
    April 2016
    March 2016
    February 2016
    January 2016
    December 2015
    November 2015
    October 2015
    September 2015
    August 2015
    July 2015
    June 2015
    May 2015
    April 2015
    March 2015
    February 2015
    January 2015
    December 2014
    November 2014
    October 2014
    September 2014
    August 2014
    July 2014
    June 2014
    May 2014
    April 2014
    March 2014
    February 2014
    January 2014
    December 2013
    October 2013
    September 2013
    August 2013
    July 2013

    Categories

    All
    Antibiotic Resistance
    Antibiotics
    Basic Concepts
    Clinical Scenarios
    Guidelines
    Infection Control
    In The News
    Microbiology

    RSS Feed

Powered by Create your own unique website with customizable templates.