Neutropaenic Sepsis Based on the 2002 IDSA Guidelines for Use of Antimicrobial Agents in Neutropaenic Patients with Cancer

Definitions Fever  Single oral temperature >/= 38.3 o C Neutropaenia  Neutrophil count < 500 cells/mm 3

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/mm 3 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/erythema No cellulitis No CXR changes No pyuria No pleocytosis in CSF

Investigations Full Blood Count and Urea/Electrolytes/Creatinine Full Blood Count and Urea/Electrolytes/Creatinine Chest X-ray Urine Culture/Microscopy Lumbar Puncture Blood Cultures Biopsy/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 InvestigationsInvestigations

CXR For patients  with signs and symptoms of a respiratory tract abnormality  managed as outpatients Not cost-effective on a routine basis Back to InvestigationsInvestigations

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 InvestigationsInvestigations

Lumbar Puncture For patients with:  suspected CNS infection  No/manageable thrombocytopaenia Not recommended as a routine procedure Back to InvestigationsInvestigations

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 InvestigationsInvestigations

Biopsy/Aspiration of Skin Lesions For skin lesions that appear infected Send for cytology, Gram staining and culture

Investigations Full Blood Count and Urea/Electrolytes/Creatinine Chest X-ray Urine Culture/Microscopy Lumbar Puncture Blood Cultures Biopsy/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?LOW risk 2.For HIGH risk patients, to start with 1 antibiotic or 2 antibiotics?1 antibiotic 2 antibiotics 3.To add vancomycin?vancomycin

Low Risk >/= 21 Extent of illness  No symptoms5  Mild symptoms5  Moderate symptoms3 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 < 39.0 o C 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 infection Outcome similar when treated with IV antibiotics in hospital Reduced costs, convenience, no IV devices required, outpatient setting Ciprofloxacin + Amoxycillin + Clavulanate Back

Monotherapy 3 rd or 4 th generation Cephalosporin or Carapenem Egs. Ceftazidime, Cefepime, Imipenem, Meropenem Many 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 + Cefepime Aminoglycoside + Ceftazidime Aminoglycoside + 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 + Cefepime Vancomycin + Ceftazidime Vancomycin + Carbapenem Aminoglycosides can also be added as a 3 rd drug. The roles of Linezolid, Quinupristine-dalfopristine and Teicoplanin are still undetermined.