Neutropaenic Sepsis

Based on the 2002 IDSA Guidelines for Use of Antimicrobial Agents in

Neutropaenic Patients with Cancer

Definitions

Fever Single oral temperature >/= 38.3oC

Neutropaenia Neutrophil count < 500 cells/mm3

At least 50% of neutropaenic patients who become febrile have an

established or occult infection.

At least 20% of patients with neutrophil counts <100 cells/mm3 have

bacteraemia

Common sites of Infection

Periodontium

Pharynx/ Lwr Oesophagus

Lungs

Vascular Catheter/Tissue around nails

Perineum/ Anus

Eye

BMA sites

Symptoms and Signs of Inflammation may be absent!

No induration/erythemaNo cellulitis

No CXR changesNo pyuria

No pleocytosis in CSF

Investigations

Full Blood Count and Urea/Electrolytes/Creatinine

Chest X-rayUrine Culture/MicroscopyLumbar PunctureBlood CulturesBiopsy/Aspiration of Skin lesions

FBC & U/E/Cr

For: monitoring drug toxicity* planning supportive care

Every 3 days during antibiotic treatment

(*Esp. for nephrotoxic drugs like amphoterecin B, cisplatin, cyclosporine, vancomycin, gentamycin etc.)

Back to Investigations

CXR

For patients with signs and symptoms of a respiratory tract

abnormality managed as outpatients

Not cost-effective on a routine basis

Back to Investigations

Urine Culture/Microscopy

For patients who have: signs and symptoms of a urinary tract infection urinary catheter in place

Little use as a routine investigation

Back to Investigations

Lumbar Puncture

For patients with: suspected CNS infection No/manageable thrombocytopaenia

Not recommended as a routine procedure

Back to Investigations

Blood Cultures

>/= 1 set of blood cultures from catheter lumen + from peripheral vein

Allows for comparison when catheter-related infection is suspected

Any fluid from an inflamed/draining catheter site should be Gram-stained/cultured for bacteria/fungi/non-TB mycobacterium

Back to Investigations

Biopsy/Aspiration of Skin Lesions

For skin lesions that appear infectedSend for cytology, Gram staining and

culture

Investigations

Full Blood Count and Urea/Electrolytes/Creatinine

Chest X-rayUrine Culture/MicroscopyLumbar PunctureBlood CulturesBiopsy/Aspiration of Skin lesions

All neutropaenic patients with fever or with signs and symptoms

compatible with an infection require prompt empirical antibiotic

therapy

Microbiology

Gram + (60%) S. aureus* S. epidermidis* S. pneumoniae* S. pyogenes* Viridans Strep* Enterococcus* Corynebacteria* Listeria monocytogenes

Gram – E. coli* Klebsiella* P. aeruginosa* Enterobacter Proteus H. influenzae

Anaerobes Bacteroides Clostridium

Vascular Access Devices

May be left in place even in catheter-related infections

Remove if: Infection is recurrent Not responsive to antibiotics after 2-3 days Tunnel infection established Bacillus, P. aeruginosa, VRE, C. jeikeium,

Acinetobacter, Candida responsible

May require debridement for atypical mycobacterium

“…no single empirical therapeutic regimen…can be recommended…many

antibiotic regimens are effective in the control of infection with minimal toxicity…

selection(should be) based on local patterns of infection and antibiotic

susceptibilities”

ISDA 2002 Guidelines

Starting Antibiotic Therapy – 3 Questions

1. Is the patient a LOW risk or a HIGH risk patient?

2. For HIGH risk patients, to start with 1 antibiotic or 2 antibiotics?

3. To add vancomycin?

Low Risk >/= 21Extent of illness

No symptoms 5 Mild symptoms 5 Moderate symptoms 3

No hypotension 5

No COPD 4

Solid tumour/no fungal infection 4

No dehydration 3

Outpatient at onset of fever 3

Age < 60 2

Other “LOW RISK” factors Absolute neutrophil count >/= 100 Absolute monocyte count >/= 100 Normal CXR, LFT, U/E/Cr Duration of neutropaenia < 7 days Expected resolution < 10 days Evidence of bone marrow recovery Malignancy in remission Peak temperature < 39.0oC No IV site infection Patient is well, no neurological changes, no

abdominal pain, no complications

Oral Antibiotics & Outpatient Management

For LOW RISK patients who have: no focus of bacterial infection no symptoms and signs suggestive of systemic

infectionOutcome similar when treated with IV

antibiotics in hospitalReduced costs, convenience, no IV

devices required, outpatient settingCiprofloxacin + Amoxycillin + ClavulanateBack

Monotherapy3rd or 4th generation Cephalosporin or

CarapenemEgs. Ceftazidime, Cefepime, Imipenem,

MeropenemMany studies show patients have better

response to meropenem compared to ceftazidime

Quinolones and aminoglycosides not recommended

Precautions for Monotherapy

Monitor for: Non-responsiveness Emergence of secondary infections Drug-resistance Adverse effects

Not active against: coag- Staph, VRE, MRSA, some strains of S. pneumoniae

Back

Two-drug Therapy

Aminoglycoside + antipseudomonal penicillin

Aminoglycoside + CefepimeAminoglycoside + CeftazidimeAminoglycoside + Carbapenem

Advantages: Synergistic effect against G- rods Minimal emergence of Drug-Resistant strains

Disadvantages: Inactive against some G+ bacteria Nephrotoicity Ototoxicity Hypokalaemia

Back

Vancomycin or not?

Indications: Suspected serious catheter-related infections Known colonisation with penicillin- and

cephalosporin- resistant pneumococci or MRSA Blood culture positive for Gram + Hypotension or cardiovascular impairment Intensive chemoRx causing substantial

mucosal damage* Afebrile neutropaenic patients on quinolone

prophylais before onset of fever*

Recommended Regimens

Vancomycin + CefepimeVancomycin + CeftazidimeVancomycin + Carbapenem

Aminoglycosides can also be added as a 3rd drug.

The roles of Linezolid, Quinupristine-dalfopristine and Teicoplanin are still undetermined.