Patient presenting with

diabetes mellitus and fever is

admitted to hospital for
diagnosis and treatment
History
A 72-year-old female who had suffered for
many years from type 1 diabetes is admitted
to hospital presenting with:
a raised temperature during the previous 8 days
malaise and muscle weakness
petechial erythema

Screening
Following a complete haematological
screening, the patient was positive for CD10
markers (CALLA
+
)
The patient was diagnosed with common
acute lymphoblastic leukaemia
Clinical course I
During a 4-month period in hospital, the
patient underwent 4 cycles of
chemotherapy with vincristine and
methylprednisolone
Clinical course II
The patient also received broad-
spectrum antibiotics at intervals to
control episodes of febrile neutropenia
The patient developed 5 episodes of
febrile neutropenia (see table in next
slide)

Clinical course II
Episode Infection Culture results Treatment
1 Pneumonia Negative Ceftazidime
2 Pseudomonas
aeruginosa
Bacteraemia Piperacillin/tazobactam
3 Pseudomonas
aeruginosa
Bacteraemia Piperacillin/tazobactam

4 None identified Negative

Cefipime/amikacin/vancomycin
5 None identified Negative

Cefipime/amikacin/vancomycin
Follow-up
One week after completing chemotherapy
the patient presented with erythema and pain
located on the left forearm in the area of insertion
of a standard intravenous (IV) cannula
the catheter was removed
the patient was neutropenic, total white blood cell
(WBC) count 1000/mm
3
,

absolute neutrophil count
100/mm
3

Follow-up
During the following 24 hours:
the patient presented with an elevated
temperature of 39C
the pain increased in severity and could
only be controlled with opioids
the patient presented with oedema in the
left forearm, which developed a dark
necrotic lesion
Inflammatory necrotic lesion
Laboratory results
Analysis of blood
haemoglobin 11.2 g/dL
haematocrit 31.8%
leucocytes 1 x 10
3
/mm
3

platelets 68 x 10
3
/mm
3

Urea, electrolytes and liver function tests
urea at 15.4 mmol/L (43.0 mg/dL)
creatinine 97.2 mol/L (1.1 mg/dL)
glucose 10.3 mmol/L (186 mg/dL)
serum glutamic-oxaloacetic transaminase (SGOT) 31 U/L
serum glutamic-pyruvic transaminase (SGPT) 17 U/L
C-reactive protein
45 mg/L (normal range <0.8 mg/L)
Clinical imaging
Chest X-ray
within normal limits
Computerised tomography
chest, abdomen and brain within normal
limits
Which of the following in your opinion is the
most probable diagnosis?


Septic thrombophlebitis (involving
Gram-positive and Gram-negative
bacilli)
Necrosis due to local extravasation of
administered chemotherapeutics
Mycosis

Which diagnostic steps
would you consider following?


Blood cultures
Samples obtained from the necrotic
tissue in the area of the forearm
Specific cultures for fungi
Histological examination of excised
tissue (biopsy of the area)
Diagnosis
Probable septic thrombophlebitis
Treatment
The patient was initially administered an
empiric regimen of
teicoplanin 400 mg IV once daily
ceftazidime 2 g IV, three-times daily
Do you agree with the treatment
combination administered to this patient?
Yes
No
Hughes WT et al. IDSA Guidelines. Clin Infect Dis 2002;34:730751
Outcome
After 3 days of antimicrobial treatment,
high fever persisted
Tissue samples and blood cultures gave
negative results for microbial pathogens
Would you change the
antimicrobial therapy now?


Yes
No
If yes, what antimicrobial treatment
would you choose now?
Monotherapy based on carbapenem
Combination of aminoglycoside with
carbapenem or piperacillin/tazobactam or
cefepime
Combination of aminoglycoside with
carbapenem or piperacillin/tazobactam or
cefepime and vancomycin

Answer
A change of treatment was
implemented
The patient was given amikacin 1.5 g IV
once daily with meropenem 1 g IV
three-times daily
Further developments
After 5 days of antimicrobial treatment,
the patient:
developed a necrotic-like lesion on the
forearm in a central position
suffered persistent pain, oedema of the
forearm and paralysis of the left upper limb
maintained a fever
The culture results remained negative
Actions
Liposomal amphotericin B 5 mg/kg/day
was added as a supplementary regimen
Due to therapy failure, the necrotic area
was broadly excised (under aseptic
conditions) which revealed involvement
of bone as well
Tissue samples were sent for culture
and histopathological examination
Necrotic lesion of the forearm
What do you think is the most likely
pathogen involved in the lesion?
Methicillin-resistant Staphylococcus aureus
Pseudomonas spp. resistant to -lactams
ESBL-producing enterobacteria
Anaerobic bacilli
Aspergillus spp.
Mucormyces

Findings
Following histopathological examination
necrotic inflammation was detected within the dermis and
hypodermal structures
fungi possessing longitudinal hyphae were found infiltrating
vessels and nerves
Positive Gomoris methenamine silver stain was
consistent with zygomycosis
Mucormycosis due to Rhizopus oryzae was
confirmed following application of specific monoclonal
antibodies against Mucormyces spp.
Histopathological manifestation
of fungal hyphae
Outcome
Tissue surgical excision in combination
with an antimicrobial regime containing
amphotericin resulted in
remission of pain and oedema
decrease in body temperature

Outcome (contd)
On day 10 following treatment:
the mobility of the patients left upper limb
improved
the dermal lesions improved dramatically
The administration of amphotericin B
was continued for 43 days
Do you believe that the selection of
antifungal treatment was
appropriate ?
Background information
Walsh TJ, Teppler H, Donowitz GR, Maertens JA, Baden LR,
Dmoszynska A, et al. Caspofungin versus liposomal
amphotericin B for empirical antifungal therapy in patients
with persistent fever and neutropenia.
National Cancer Institute, National Institutes of Health,
Bethesda, MD, USA. N Engl J Med 2004;351:1391402
Klastersky J. Antifungal therapy in patients with fever and
neutropeniamore rational and less empirical? N Engl J Med
2004;351:14451447.
Apisarnthanarak A, Little JR, Tebas P. Voriconazole versus
liposomal amphotericin B for empirical antifungal therapy.
N Engl J Med 2002;346:17451747; author reply 17451747

Key learning points
Consider a broad range of infections in an
immunocompromised patient
Consider all potential pathogens (not just bacteria)
Alter empiric therapy promptly if the patient does not respond
Histopathology and immunohistochemistry can provide
answers that tissue samples and blood cultures do not
Core principles applied to this case
It is important to start with the appropriate
empiric antibiotic first in nosocomial infections
Administer antibiotics at the right dose for the
appropriate duration
Recognise that prior antibiotic administration
and previous hospitalisation (as well as
catheterisation) are risk factors for the
presence of resistant pathogens