Controversies in managing neonatal infections

David Isaacs

Children’s Hospital at Westmead

Sydney Australia

Controversies in managing neonatal infections

• Should I start antibiotics?

• Should I do a lumbar puncture first?

• Which antibiotics?

• Reluctance to stop antibiotics.

• How can I prevent fungal infections?

• How can I prevent coagulase negative staphylococcal

infection?

Should I start antibiotics?

• Maternal risk factors in early sepsis

• Clinical examination

• Laboratory: blood count, acute phase reactants

• If in doubt, start them

Immediate

• Biopsy: alters treatment

in 25% (Ecoli)

• 15-40% with meningitis

have negative blood

cultures

• Avoids confusion

Delayed

• Respiratory compromise

• Trauma

• Cerebral herniation

• Rare

Should I do a lumbar puncture first?

LP and possible early sepsis

• Baby with RDS:

0.3% have meningitis

1500 LPs to find one meningitis

• Indications for Selective LP

Clinical suspicion

Risk factors (greatly prolonged rupture)

• Wiswell, 1995

169,000 babies: Selective LP would mean delay or missed diagnosis in 16 of 43 babies (37%)

LP and late sepsis

Traditional data: up to 10% of babies with late sepsis have meningitis

Recent data: 50-60% of late sepsis is with coagulase negative staphylococci

Inclination:

• take blood culture, urine but not CSF (unless very sick)

• start antibiotics

• LP only if blood growing likely meningitis pathogen

Which antibiotics?

Narrowest spectrum possible:

• Penicillin and gentamicin

• Flucloxacillin and gentamicin

• Vancomycin and gentamicin

Not third generation cephalosporins

Not imipenem or carbapenem

Antibiotic abuse

Paper to review:

• European country

• Thanksgiving

• 30 babies treated for Pseudomonas infection with

ciprofloxacin

• Used ciprofloxacin because had run out of other options

• Only 4 had sepsis; 26 had endotracheal tube isolates

• Treated for 8 to 30 days

Antibiotics abuse (cont)

• Treating colonisation not sepsis

• Treating for long periods of time

• Using very broad spectrum (and expensive) antibiotics

Good antibiotic practise

• Use narrowest spectrum antibiotics possible

• Treat sepsis, not colonisation

• Stop antibiotics if cultures negative

Reasons given for continuing antibiotics

• Baby looked sick

• Acute phase reactants elevated

• Cultures might be false negatives

• Cultures unreliable

• Culture results not back

Antibiotic use, Oxford 1984-6(ADC 1987: 62: 727-8)

1984 1986

Mean duration of antibiotics 5.5 days 3.6 days

Weight of antibiotics (g) 202.7 122.1

% treated 50% 42%

Late sepsis 12 16

No. after stopping antibiotics0 0

Reasons for stopping antibiotics

• Baby looked sick

• Courage, other causes

• Raised CRP

• Stop measuring it

• False negative cultures

• Rare in late sepsis

• Results not back

• Go to the lab and ask

How do I prevent fungal infections?

• Reduce duration of antibiotics

• Reduce duration of parenteral feeding

• Prophylactic antifungals

Fluconazole prophylaxis(Kaufman et al, NESM 2001; 345: 1660-6)

100 babies < 1000g BW over 30 month period

50 IV fluconazole for 6 weeks

50 placebo

Fluconazole Placebo

Colonisation 11 30

Infection (urine, blood, CSF) 0 10

Prophylactic oral nystatin

Preterm babies, birthweight <1250g

Oral nystatin 1mL (100,000U) 8-hourly until one week after extubation.

Outcome: colonisation (oropharynx, rectum)

sepsis (blood, urine)

(Sims M et al. Am J Perinatol 1988; 5:33-6)

Prophylactic nystatin for low birthweight babies

Nystatin Control P

(n = 33%) (n = 34)

Colonised : 4 (14%) 15 (44%) <0.01

Systemicinfection : 2 (6%) 11 (32%) <0.001

UTI : 2 (6%) 10 (30%) <0.01

Pneumonia : 0 1 (died)

Candidaemia : 0 2(Sims ME. 1988)

How can we prevent coagulase negative staphylococcal sepsis?

• Change question:

• Should we try to prevent CoNS sepsis?

Coagulase negative staphylococcal neonatal infection

(Australasia 1991 - 2000)

• 1,281 episodes

• 57% of late sepsis

• Meningitis 5 (0.4%)

• Mortality 4 (0.3%)

Conclusions

• Antibiotics are an extremely valuable resource

• Use them wisely

• Use them sparingly

• Prevention important

• Over-vigorous prevention not always wise