See Practical for diagnosis of infection.
BMJ 2004;329:1277-1280 Clinical review - (ABC of preterm birth) Infection in the preterm infant
GBS emerged in 1960s, replaced GAS in neonatal sepsis. More common in US and Australia, very variable in UK (about 25% but all depends on what cultures you take). Associated (in UK at least) with VLBW. Protective antibodies develop in about half of colonized women by 34/40. Nonetheless, neonatal infection carries 10% mortality, 50% morbidity rate. Risk factors eg prematurity, prolonged rupture of membranes >24hrs, previous carriage predict 60% of cases.
No RCT comparing risk based and universal screening based policies. Screening associated with less early onset disease so used in US. Tends to be easier to give antibiotics, esp since mums will present earlier if aware, but about 30% of all mums eligible! NNT = about 1000 to prevent 1 case. Dangers are anaphylaxis, changes in bowel flora, antibiotic resistance.
RCOG strategy is for selective intrapartum prophylaxis. Indicated for previous baby with neonatal GBS infection, should be considered if known carriage in current pregnancy, and says that " argument for prophylaxis becomes stronger" where 2 risk factors present:
The definition of preterm labour will significantly affect the number of mums/babies who receive intervention, depending on local statistics. PROM without labour does not require treatment; elective section does not require treatment.
For babies, RCOG guideline gives choice of clinical evaluation and observation for 12hrs or blood cultures and penicillin. If a mum has been febrile in labour, suggesting chorioamnionitis, then the baby should probably be treated as potentially infected with a range of different organisms, not just GBS.
Cochrane shows that intrapartum antibiotics protect baby from early onset only (about 60% effective). No reduction in late onset, which is probably related to horizontal transmission. So if colonization is picked up late ie after 48hrs, probably no point in offering prophlyaxis.
Some evidence that prophylaxis is leading to increased gram negative sepsis - although overall incidence and mortality are less. Some evidence of more late onset sepsis esp with ampicillin resistant organisms (case control study) Pediatrics. 2005 Sep;116(3):696-702 [16140710], NEJM 2002, Stoll [12140299]. but metanalysis has come down against increased non GBS early sepsis.
Certain serotypes eg 3 predominate. Now phase 2 conjugate vaccine, but risk of shift in types, and ?teratogenicity of immunizing in pregnancy.
Early onset (ie in first week, but mostly in first 24 hours and about half symptomatic at birth) usually present with tachypnoea - pneumonia, septicaemia mostly but 10% meningitis. Late onset is much more likely to be meningitis (35%), but septicaemia still common. Rx 10/7, 14/7 for meningitis. Not as sensitive to penicillin as GAS so needs high dose.
Probable early-onset group B streptococcal (EOGBS) infection can be defined as colonisation by group B streptococci accompanied by features of clinical sepsis. Data collected prospectively in the UK over 1 year for neonates who required a septic screen in the first 72 h of life indicated a combined rate of definite and probable EOGBS infection of 3.6 per 1000 livebirths. This estimate indicates a much greater disease burden in the UK than that suggested by figures of culture-proven sepsis, and lends support to the need for prevention strategies.
No benefit in neonatal meningitis from steroids.
MRSA sepsis in NICU has 25% mortality. Early onset staph sepsis (non-MRSA) has 39% mortality, mind you. (Australia, Arch Fet 2004)
Linezolid is as effective and better tolerated than vancomycin. Side effects are haematological.
12% of neonates with Staph aureus bacteraemia have infective endocarditis on modified Duke's criteria, but mostly these are associated with congenital heart disease. Mortality rises to 40% with endocarditis.(Pediatrics. 2004 Dec 15)
Notifiable! Chlamydia probably the most common, but also Group B strep, gonococcus, etc. In some countries babies are routinely treated with topical silver nitrate, which prevents transmission of gonococcus but not of chlamydia. Test and treat for both chlamydia and gonococcus pending results. Topical Neomycin preferred to chloramphenicol or gentamicin for non-STI cases in neonates (BNFc). Remember to initiate STI screening for mum and sexual partners where appropriate.
Ophthalmia presents at 5-14/7, mucopurulent, pseudomembrane adherent to conjunctiva. Non scarring cf trachoma (different serovars of chlamydia).
Increased risk of premature delivery. Can cause neonatal afebrile pneumonia, presents at 10-100/7. No wheeze cf bronchiolitis. ?eosinophilia. Asympt coloniz for up to 3yr!
Diagnosis: Swab everted eyelid for EIA, PCR (but do twice with different primer in sex abuse cases). Urine PCR not as sensitive but good for screening mum.
Treat with oral erythromycin for 14 days. Topical treatment cures ophthalmia but does not eradicate carriage and pneumonia may develop later. Cure rate is only about 80% so test at end of treatment and be prepared to give another course or 2 if necessary. There is limited experience of using azithro. Treat pregnant mum with Amox or single dose Azithro but check for cure at 3/52. Immunity short lived & serovar specific. NB V high reinfection rate (?relapse).
Has potential to cause perforation of the globe as well as disseminated infection (oropharynx becomes colonized, as for meningococcus). Signs usually develop from day 2 onwards, with prominent oedema and purulent discharge. Gram stain will show gram neg diplococci for gonococcus (but differential includes moraxella and other neiserrias so don't jump to conclusions). If unwell, do LP and blood cultures too. Single-dose ceftriaxone 50mg/kg (max 125mg) unless jaundiced, in which case single dose cefotaxime 100mg/kg IM or IV. N Engl J Med. 1986 Nov 27;315(22):1382-5.
Abundant neutrophil precursors at term, but limited ability to increase proliferation so infection often causes rapid depletion of pool. No evidence for granulocytes infusion in sepsis (but small numbers) - too late anyway? G(M)-CSF promote production, survival and function: levels lower in preterm, plus less complement & Ig in serum, fewer receptors, killing defects. Therapeutic use reduced mortality in septic neutropenic preterms. Benefit was nonsignificant when used prophylactically (but PROGRAMS study was supposed to report back...)
Nadir in IgG @ 4/12. Gradual climb in IgA/M from term up to 12/12 (?beyond too?). Risks of IVIg - HCV was transmitted before its recognition, Prion risk uncertain. Inactivation steps in manufacture. Used prophylactically, it decreased sepsis (approx 3% incl serious) but not mortality in preterm/LBW. Used therapeutically, it decreased mortality in proven infection but not signif across all cases. NB different products/regimens...
Stool microflora in prems consists of CNS and candida! Rarely the usual lactobacilli or bifidobacteria. Gene expression in the gut is driven by colonising organisms, so this abnormal flora likely to have profound implications for immunity. The gut mucosal surface area is about 200x the skin surface area, hence clearly the most important source of bugs. Note that the usual vaginal delivery style encourages transfer of normal flora from mum to baby...!
3rd most common cause of late onset sepsis in VLBW. Mostly albicans, but parapsilosis (assoc with health care workers) and glabrata also feature. GI colonization followed by translocation. Associated with broad spectrum antibiotics esp 3rd gen cephalosporins, venous catheters, lack of enteral feeding and extreme prematurity. Systemic spread is the rule - any one organ affected should prompt evaluation of others esp kidney, CNS, eye, heart, joints.
Failure to remove central lines within 24 hours of positive blood culture for candida increases mortality.
Treat with Ambisome or Fluconazole (just as good if susceptible - C. glabrata, krusei are often resistant). Consider caspofungin.
PIDJ Volume 24(9), September 2005, pp 831-832. Pediatrics. 2006 Jan;117(1):84-92.
Once colonized, the usual risk factors apply for progression to sepsis eg birth weight, bacterial sepsis, intubation. On logistic regression, central venous catheter colonization and multiple-site colonization are independent risk factors. Fluconazole prophylaxis is an independent protective factor (Pediatrics. 2006;118:2359-64). Nystatin prophylaxis has also been demonstrated to be effective Arch Dis Child Fetal Neonatal Ed. 2008 Nov 26, PMID: 19036756).
But is background rate high enough to make routing prophylaxis worthwhile? Esp if 3rd gen cephalosporins are not used as empirical treatment Pediatrics. 2006 Jan;117(1):e22-32. Epub 2005. Pediatrics. 2006 Jan;117(1):67-74. High risk eg VLBW getting broad spectrum antibiotics for more than 3 days gives NNT=10 Lancet May 2006
Leuconostoc has been reported as a cause of gram positive sepsis with vancomycin resistance. Treat with Ampicillin and gentamicin (Am J Perinatol. 2008 Nov 21 PMID: 19031357). Vancomycin resistant enterococci have also been described.
See also Basic microbiology for more on antibiotic resistance.
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