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16 Infection Key points ■■ ■■ ■■ ■■ ■■ ■■ ■■ Meticulous hand washing and the use of alcohol gel is the best way to prevent crossinfection in a neonatal unit. Infection remains an important cause of morbidity and mortality at all birth weights and gestations, but is particularly important in very preterm babies. Perinatal infection is an important contributor to neuronal damage and adverse outcome in preterm babies, even without meningitis (‘cytokine’-mediated damage). The bacterial organisms that most commonly infect babies are group B betahaemolytic Streptococcus and Escherichia coli, with coagulase-negative staphylococci a frequent cause of late-onset sepsis in very low birth weight babies. Any baby suspected of sepsis must have investigations, including a blood culture, carried out immediately, and antibiotics (usually penicillin and an aminoglycoside) started straight away. Although herpes infection is rare, it is important to think of the diagnosis and start intravenous aciclovir; one clue is the absence of bacterial organisms on a gram stain of cerebrospinal fluid (CSF) when the CSF also contains a high number of white cells in a baby who has not been previously treated with antibiotics. Neonatal bacterial meningitis has a high risk of adverse outcome. All cases should be managed in large centres with appropriate expertise. ■■ Infection control in neonatal units Babies usually emerge from a sterile intra-uterine environment, and it follows from this that most infections in babies admitted to neonatal units (NNUs) are hospitalacquired, or nosocomial, infections. The risk of nosocomial infection is directly proportional to the number and crowding of babies in the unit, the number of infections in those babies, and the number of people (visitors and staff) going in and out of the unit. Staff who are overworked have less time for hand washing. NNUs should be spacious and designed so that only those who need to enter them pass through, and with plenty of sinks. Babies should be admitted to the NNU only if absolutely necessary, and staffing levels should be maintained. Scrupulous attention to hand washing is the single most important factor in the prevention of cross-infection. Hands and forearms should always be washed with a suitable preparation, dried and alcohol gel applied before and after handling a baby. Gel should be applied after touching notes, keyboards or door handles. Watches and jewellery must be removed so that staff are ‘bare below the elbows’. There is no evidence that the use of gowns, masks and overshoes by staff or parents makes any difference to the level of cross-infection in an NNU. Gowns and masks should be used only when it is necessary to protect the staff during outbreaks of serious infection. 185 927717_MONIC_Ch16_185-216.indd 185 6/3/13 9:34 PM Staff with a current infectious disease such as a respiratory illness, boils, gastroenteritis or weeping dermatitis should be excluded from the unit. Staff with cold sores or herpetic whitlows should cover them, treat with aciclovir and cannot work in a clinical area until the lesions have crusted over. Mothers with wound infections, cold sores, vaginal discharge or known pathogens on their high vaginal swab (HVS) should be allowed in, but any exposed lesions should be covered and their hand washing should be supervised and particularly fastidious. Topical aciclovir should be applied to any cold sores. Mothers of babies with Listeria are inevitably faecal carriers and should be isolated themselves, as should their affected baby. Communal equipment such as stethoscopes and thermometers is a major source of cross-infection. Individual pieces of equipment must be provided. Disposable equipment should be used where possible, for example blood pressure cuffs. Neonates with infections which could be a hazard to other babies should be nursed in separate rooms if possible. An incubator provides a moderately secure microenvironment for most infected neonates if the hand-washing technique is rigorous, and is adequate for asymptomatic carriers of pathogenic organisms. When confronted by epidemic infectious disease (e.g. recurrent Serratia septicaemia or enterovirus infections), there is no alternative but to close the unit to new admissions. Occasionally outbreaks of particular organisms require investigation to locate them, or a change in practice to eradicate them – e.g. Pseudomonas can contaminate taps, and gentamicin resistance can spread rapidly between different gram-negative organisms requiring a change of first-line antibiotic policy. With the current trend to early discharge, babies can be readmitted to the NNU from the community, but we would always ‘isolate’ such infants in incubators pending surface swabs and cultures. Babies who require readmission and who have symptoms of viral infections such as respiratory syncytial virus (RSV) must not be readmitted to NNUs unless they can be isolated, as epidemics can follow. Viral infections can be life-threatening to babies with chronic lung disease (CLD). ■■ Host defences in the newborn and the inflammatory response The newborn baby has a ‘good enough’ immune system for his needs, which are usually limited. He depends on his mother for ‘immune protection’ via transplacental antibody transmission and the protection provided by breast milk. The newborn immune system, like that of the adult, can be described as ‘innate’ and ‘adaptive’ (Table 16.1). The system is ‘downregulated’ in the newborn, but the baby is still capable of mounting a robust, even an exaggerated, pro-inflammatory response to infection in some circumstances. It is this inflammatory response, involving interleukins and other cytokines, which is thought to be potentially damaging to neuronal development, particularly the pre-oligodendrocytes. These are the cells which will make myelin when fully mature. Both the fetal and neonatal inflammatory response have been linked to brain injury in preterm babies, and babies who have mounted an inflammatory response at term may be ‘preconditioned’ and more susceptible to hypoxic ischaemic injury than entirely healthy babies (Malaeb and Damman 2009). Infection Physical defences The neonatal skin is very thin, easily damaged and infected. The umbilical stump becomes necrotic after birth and acts as a locus for infections which can then disseminate. The passage of an endotracheal tube, a nasogastric tube or an intravascular catheter provides a route for pathogenic organisms to enter the body. 186 927717_MONIC_Ch16_185-216.indd 186 6/3/13 9:34 PM Characteristics Components Innate Adaptive Non-specific response Highly specific response Response is fast (minutes) Response is slow (days) Has no memory Has memory Natural barriers, e.g. skin Complement Neutrophils and macrophages Pattern-recognition molecules, e.g. Toll-like receptors and Nod proteins on dendritic cells T and B lymphocytes Major histocompatibility complex restricted antigenrecognition molecules The newborn baby is virtually germ-free at birth, apart from organisms that become smeared over him as he passes through the vagina. He therefore lacks the protection afforded by having a resident flora of non-pathogenic organisms. A normal neonate is colonized by generally non-pathogenic organisms acquired from his mother, including those in her vagina and rectum, to which he was exposed during delivery. However, particularly if he is in an NNU, he may also be colonized by, and subsequently infected with, potentially pathogenic organisms acquired from the hospital environment. The gut is a particularly important organ in this respect due to gut-associated lymphoid tissue, and early feeding with fresh ‘mother’s own’ breast milk is a very important way of establishing a colony of ‘friendly’ bacteria. Approximately 80% of the body’s entire immune system is in the intestine, and nutrition and immune function are closely linked in the newborn period (and remain so throughout life). Much current research is directed at evaluating the role of probiotics in preventing gut-associated lymphoid tissue (necrotizing enterocolitis (NEC)). Probiotics are strains of ‘friendly’ bacteria such as Lactobacillus CG or Bifidobacterium given by mouth, which multiply in the gut and colonize it. However, concerns remain about the emergence of resistant strains, cross-colonization in the nursery and the possibility of septicaemia due to the strain used (Millar et al. 2012). Host defences in the newborn and the inflammatory response Table 16.1 Comparison of innate and adaptive immune systems Cellular immunity Cells involved in the immune system are macrophages, neutrophils, eosinophils and mast cells. Lymphocyte function is well developed even in the 28-week fetus. The absolute number of T-cells present is similar to adult values. T-cells are able to mount a response from the third trimester, and antigen-specific T-cells are found in cord blood. A full complement of B-lymphocyte types is present by the end of the second trimester, and these cells can respond by synthesizing antibodies, although their function is still suboptimal (De Vries et al. 1999). A swift antibody synthetic response by the neonatal lymphocyte is dependent on the presence of some immunoglobulin G (IgG) in the plasma to help process the antigen. The response of the neonate will be improved if he has an adequate level of transplacental maternal IgG. Phagocyte function Polymorphonuclear leucocytes from healthy preterm and full-term babies when suspended in normal adult serum show normal phagocytosis and bactericidal activity, but some reduction in chemotaxis and adherence. There is some evidence that phagocytic ability against Escherichia coli is less in cells from cord blood than at 3 days of life, when it reaches adult levels. 187 927717_MONIC_Ch16_185-216.indd 187 6/3/13 9:34 PM Humoral immunity The normal neonate, irrespective of gestation, has virtually no circulating IgA, IgD, IgE or IgM. If any of these are present in cord blood or the early neonatal period, they have been manufactured by the fetus and imply fetal infection. In general, IgA responses protect against inflammation, while IgG is more pro-inflammatory and serves to ‘opsonize’ bacteria (make them more ‘tasty’ to phagocytes). IgE responses may also promote inflammation by disrupting epithelial barrier and neural function. IgG, meanwhile, is both actively and passively transported across the placenta from about the twentieth week of gestation, and by full term the baby’s IgG level is higher than that of his mother. Following delivery, the level of IgG in the baby’s plasma falls with a half-life of about 3 weeks, and until he produces adequate amounts of IgG, IgM and IgA there is a transient postnatal hypogammaglobulinaemia. This is rarely clinically important in a term baby, but a premature baby is born before much IgG has crossed the placenta and is therefore at increased risk of infection from the time of birth for several weeks until after the postnatal hypogammaglobulinaemia has been corrected. At the trough, about 3–4 weeks after delivery, the preterm baby may have IgG levels less than 0.2 g/L. Since the neonate acquires his IgG from his mother, he is immune to the infections to which she is immune, except for those conditions in which immunity is IgM mediated or cell mediated (E. coli, tuberculosis (TB)). The levels of the components of the complement cascade and the alternative complement pathway in the neonate are 50–80% of adult values, and even lower in premature babies. The neonate is technically immunodeficient because he lacks these defence mechanisms. However, it is important to recognize that he is immunocompetent since he can, and does, respond to the antigenic challenges he receives postnatally, particularly if he has adequate levels of IgG. ■■ Bacterial infection in the newborn The major bacterial pathogens now encountered are E. coli, the group B β-haemolytic Streptococcus (GBS; Streptococcus agalactiae) and Staphylococcus epidermidis (coagulase-negative staphylococci (CONS)), which are responsible for 80–85% of severe neonatal infections. Many NNUs contribute data to national or international infection-surveillance networks, which are able to monitor changes in infecting pathogens and antibiotic resistance over time. The UK NeonIN data demonstrate that, with the inclusion of CONS, the incidence of all neonatal infection is 0.8% of live births. Other bacteria which are commonly responsible for serious infection are: 1. Pseudomonas aeruginosa; 2. other gram-negative bacilli (Klebsiella, Proteus, Enterobacter, Haemophilus); 3. Staphylococcus aureus; 4. Pneumococcus and other streptococci (groups A, D, G and viridans); 5. Listeria monocytogenes; Infection Superficial infections Bacterial infection of the umbilicus and skin Effective umbilical cord care is important. Maternity units no longer treat the umbilical cord stump with antibiotic powder or spray, but the umbilicus should be kept clean and dry. A slightly sticky cord can usually be treated with alcohol wipes. 188 927717_MONIC_Ch16_185-216.indd 188 6/3/13 9:34 PM Bacterial infection in the newborn If infection does occur, with periumbilical redness and local discharge, it is usually due to staphylococci or E. coli. Systemic antibiotics are indicated if the discharge is copious or oedema and inflammation are spreading onto the abdominal wall. Staphylococcal skin infection is now rarely seen. It is important to recognize the condition of neonatal pustular melanosis for the benign condition that it is, and not to treat these babies with antibiotics. Neonatal pustular melanosis is quite common in babies with deeply pigmented skin, and the rash is present at birth. In addition to the pustules, look for older lesions with a freckle-like appearance and a flaky collar to them; characteristically, there are lesions at different stages of development. All paediatricians should also be familiar with the appearance of erythema toxicum. Occasionally toxic epidermal necrolysis (Ritter’s disease) develops. This responds to adequate parenteral fluid replacement and intravenous flucloxacillin. Group A Streptococcus can cause extensive tissue loss owing to ‘nectrotizing fasciitis’ and toxic shock, resulting in very serious illness, albeit rare. Thrush (usually Candida infection) This is usually a trivial oral or perianal infection in otherwise healthy term babies. It presents as white plaques on the buccal mucosa and tongue which cannot be wiped off, or as the typical bright erythematous perianal rash with discrete lesions looking like the base of thin-roofed blisters, lying peripheral to the confluent rash. This usually responds promptly to treatment with topical miconazole gel or nystatin suspension. Thrush is more common in very low birth weight (VLBW) babies who are on broad-spectrum antibiotics for a prolonged period of time, especially if they are also receiving steroids for CLD (see Chapter 14). In such babies systemic candidiasis may occur. We use prophylactic fluconazole intravenously in babies of birth weight less than 1 kg with long lines or umbilical catheters in place, and there is some evidence to support this practice. Conjunctivitis The diagnosis and management of this condition is outlined in Table 16.2. Superficial abscesses These develop at the site of intravenous infusions, heel sticks or any other place where the skin is damaged. The local lesion is obvious, but care should be taken to ensure that Table 16.2 Management of neonatal conjunctivitis Organism Age at presentation Diagnosis Treatment Gonococcus 1 day (some recognized in 1st week) Maternal history Single dose of ceftriaxone, 25– 50 mg/kg IV or IM to a maximum dose of 125 mg is effective and topical treatment is not then necessary. Older regimens of IV and topical penicillin are also effective. Notifiable disease. Remember to isolate baby with mother, organize treatment and contact tracing for mother Profuse conjunctival discharge Urgent gram stain on pus shows gramnegative intracellular diplococci. Culture of swab sent in transport medium (continued ) 189 927717_MONIC_Ch16_185-216.indd 189 6/3/13 9:34 PM Table 16.2 (Continued) Organism Age at presentation Diagnosis Treatment Chlamydia trachomatis 5 days or more No distinguishing clinical features. May be maternal history Systemic erythromycin (45 mg/ kg/24 h in three divided doses) for at least 2 weeks to prevent pneumonia. Well absorbed orally. Also use 1% chlortetracycline eye ointment or drops Conventional cultures can be sterile. Antigen detected in eye swab by immunofluorescence Others; most common are Staphylococcus aureus, Escherichia coli, Haemophilus, Streptococcus pneumoniae 3–5 days peak, but may be at any time including day 1 Culture of swab If mild, sterile saline cleaning. If discharge persists for more than 48 hours and there is lid oedema, use chloramphenicol eye drops IM, intramuscular; IV, intravenous. the underlying bone is not affected. If fluctuant, the abscess should be aspirated and the pus sent for gram stain and culture. The other routine investigations for infection should also be carried out (pp. 192–193). Treatment with intravenous flucloxacillin and gentamicin should be given initially for 7 days or until the lesion is healed. Systemic bacterial infection The comparative immunodeficiency of neonates not only predisposes them to infection but also means that when infection occurs it may disseminate rapidly, with septicaemic shock and death occurring within 12 hours of the first signs of illness. This dissemination, which is particularly rapid in the most immature, has two major implications: 1. Early diagnosis is essential. Even very trivial clinical findings that suggest infection demand full laboratory evaluation. 2. Initial therapy must be started on the basis of clinical suspicion. There is not time to wait for the laboratory results to come back 24–48 hours later. Shrewd and vigilant observation by the nurses and parents who are with the babies all the time is the cornerstone of early diagnosis. Woe betide the neonatal resident who ignores such observations made by an experienced nurse. History Infection Apart from verifying the presenting history, the following points should always be checked: 1. Is the baby compromised in any way that would predispose him to infection (e.g. very premature, indwelling catheter, endotracheal tube)? 2. Was there anything in the perinatal history suggesting an infectious risk (e.g. maternal illness or pyrexia, prolonged rupture of membranes, pathogens known in the mother’s HVS)? 3. Is there a risk of nosocomial infection from relatives, staff or other sick babies on the unit? 190 927717_MONIC_Ch16_185-216.indd 190 6/3/13 9:34 PM Temperature change. Hypothermia and hyperthermia are often due to deficiencies in the control of the environmental temperature (Chapter 7). A body temperature below 36°C or above 37.5°C sustained for more than an hour or two in an appropriate environmental temperature is due to infection until proved otherwise. The higher or lower the temperature, the more significant it is. ■■ Reluctant to feed. When a term baby is reluctant to feed from breast or bottle, infection should be suspected, particularly in a baby who was previously feeding well. ■■ Listlessness, lethargy, hypotonia, pallor, mottled skin. These are often the first, mild, non-specific signs that a baby is unwell. The baby just does not seem ‘right’. Very preterm babies are often described as ‘not handling well’ or ‘going off’ – nonspecific terms that neonatal nurses use when the baby has an increase of apnoeas and bradycardias, particularly when moved or touched. ■■ Irritability. A baby who is irritable and will not stop crying or whimpering, even for a feed, may be developing septicaemia or meningitis. A high-pitched monotonous cry is a neonatal danger sign. ■■ Jaundice. If this develops rapidly in a baby without haemolytic disease, sepsis is present until proved otherwise, although the yield of infection screens when jaundice is the only presenting sign in a well baby is very low. ■■ Vomiting. If persistent, this is suggestive of infection (as well as intestinal obstruction). Diarrhoea and vomiting are not necessarily signs of gastroenteritis in neonates, and are much more commonly non-specific features of early infection. ■■ Ileus/intestinal obstruction. Sepsis may present as vomiting, abdominal distension and constipation due to an ileus, particularly when there is intra-abdominal infection (e.g. NEC, pp. 278–283). ■■ Pseudoparalysis. The lack of movement owing to limb pain may alert the clinician to the presence of arthritis or osteomyelitis before local or generalized signs develop. ■■ Apnoea. Commonly the first sign of infection in premature babies. ■■ Tachypnoea. Tachypnoea accompanying any of the above signs is often the first sign of pneumonia or septicaemia. ■■ Cardiovascular signs. Tachycardia is common in any infection and marked in cardiac infections. Delayed capillary filling is a useful early sign. Skin blanched by pressure should return to normal colour within 1–2 seconds. ■■ Bacterial infection in the newborn Early symptoms and signs Late signs and symptoms These are usually specific to one organ system. If infection presents in this way it suggests that the diagnosis could have been made earlier if the baby had been more carefully and expertly observed. Respiratory: cyanosis, grunting, respiratory distress, cough. Abdominal: bilious or faeculent vomiting, gross abdominal distension, livid flanks, indurated abdominal skin and periumbilical staining, absent bowel sounds. ■■ central nervous system (CNS): high-pitched cry, retracted head, bulging fontanelle, convulsion. ■■ Haemorrhagic diathesis: petechiae, bleeding from puncture sites. ■■ Sclerema: this is a late feature of any serious illness, especially in preterm neonates. It has no specific significance or specific therapy. ■■ ■■ 191 927717_MONIC_Ch16_185-216.indd 191 6/3/13 9:34 PM Clinical examination The baby should be completely undressed and carefully examined, paying particular attention to the following points: 1. 2. 3. 4. 5. 6. Confirm the presenting signs (e.g. fever, jaundice, pallor, grunting). Are there any lesions on the skin, subcutaneous tissues or scalp? Is there periodic breathing or tachypnoea at rest? Is there tachycardia or murmurs suggesting cardiac disease? Are there added sounds on auscultation of the chest? Is there hepatosplenomegaly which accompanies generalized infection as well as hepatitis? 7. Is there kidney enlargement? Cortical swelling of the kidneys may be present in early septicaemia as well as urinary tract infection (UTI). 8. Is the umbilicus red and tender with a thickened cord of inflamed umbilical vein extending up the falciform ligament? 9. Can osteomyelitis and arthritis be excluded by the presence of full and painless limb movements? 10. Are bowel sounds present? Does the baby cry during palpation of his abdomen, suggesting peritonitis? 11. Meningism is rare in neonatal meningitis, but check the back and skull for pits or other skin defects that might be the entry site for spinal infection. 12. Assess the baby’s overall neurological state. 13. Babies do not have dysuria or frequency, but with pyelonephritis they may have loin tenderness which can be detected by gentle pressure on the renal angle. 14. Is the baby dehydrated? Has he lost more than 10% of his birth weight, suggesting major gut fluid loss? Investigations Infection Whenever there is any suspicion of infection on the above features, the following tests should always be carried out: 1. Take swabs. There is little benefit from taking swabs from any site other than the ear and throat when assessing babies in the first 6–12 hours. Gastric aspirate reflects the liquor and the contents of the birth canal, is not helpful after the first feed, and has largely been abandoned. Swab any skin wound or spot. Remember viral cultures. 2. In the presence of early-onset sepsis, a maternal HVS should always be cultured. 3. In late-onset sepsis or NEC, stool culture or rectal swabs can be helpful. 4. Endotracheal tube aspirate (if applicable). 5. Bag urine in investigation after 24 hours of age. The vulva or penis should be cleaned as carefully as possible and any infection noted, to assist interpretation of the result. The urine should be decanted from the bag into a sterile container as soon as possible after voiding. Results from bag specimens of urine collected from neonates should always be viewed with grave suspicion unless pus cells or bacteria were seen immediately on examination of the sample. If any doubt exists, urine must be obtained by suprapubic bladder puncture. 6. Blood culture. The ‘gold standard’ test. Use a strict aseptic technique with a closed system and aim for at least 0.5 mL of blood. Great care should be taken in interpreting positive results when more than one organism is grown or the organisms grown are also skin commensals. Unless these grow in pure culture within 24–48 hours, they are probably contaminants. 192 927717_MONIC_Ch16_185-216.indd 192 6/3/13 9:34 PM Bacterial infection in the newborn 7. White blood cell (WBC) count and differential. Polymorph counts above 7.5–8.0 × 109/L (7500–8000/mm3) or below 2 × 109/L (2000/mm3), more than 0.8 × 109 myelocytes/L (800/mm3) an I:T ratio of >0.2 (the ratio of immature to total neutrophils) and a left shift or toxic granulation of the white cells are all suggestive of neonatal bacterial infection after the third day of life, but the range is wide. On the first day of life a polymorphonuclear leucocytosis is not usually due to infection, but neutropenia, an I:T ratio of >0.2 and the presence of immature cells, and toxic granulation are. Thrombocytopenia (<100 × 109/L) is common in infected babies. 8. C-reactive protein (CRP). A CRP above 10 mg/L suggests infection, but the levels often take 12 hours to rise. The CRP doubling time is 8 hours, and the half-life is about 19 hours. CRP is more helpful for monitoring progress than for establishing the diagnosis. The following investigations should also be carried out in most situations: 1. Lumbar puncture: this should be carried out in all babies with suspected sepsis with the exception of babies with respiratory distress syndrome in whom antibiotics are started at birth (p. 149) or those with CLD on intermittent positive pressure ventilation (IPPV) who develop lung infection (p. 174). 2. Chest X-ray (CXR): this often gets forgotten – unwisely! CXR should be done unless there is an obvious extrapulmonary focus of infection. 3. Abdominal X-ray: if the symptoms suggest intra-abdominal pathology, if there is any abdominal distension, or if there is blood in the stool. The main diagnosis of importance is NEC. 4. Blood gases: a metabolic acidaemia is often present in severe infections, and if the base deficit is above 8 mmol/L not only does it suggest sepsis but it may need correction. Hypoxia, hypercapnia or apneoic attacks are indications for ventilation in sepsis. 5. The plasma electrolytes, urea, glucose, calcium and albumin should also be checked – not only may they be abnormal when sepsis presents, but also a baseline measurement is important when planning fluid and electrolyte balance in the next few days. Interpretation of results When the baby first presents, a quick decision has to be made about whether or not to treat with antibiotics. Of the tests initially carried out, those which give the definitive answer – the cultures – take 24–48 hours to come back, so neonatologists have to rely on tests with a turn-around time of an hour or two to help them make that decision. Basically, if there has been a good reason to perform the infection screen in the first place then antibiotics should be started. If in doubt, treat Treatment of systemic bacterial infection Antibiotics Any baby in whom it is remotely possible that an infection is responsible for the abnormal clinical and laboratory findings should be given antibiotics. These can be stopped in 2 days if the baby’s condition rapidly improves and cultures are negative. CRP is particularly helpful in this regard; there is a lag in the rise, but if the level remains below 10 mg/L, bacterial infection is unlikely. Taken together with negative culture results (or culture results suggesting contamination) in a well baby, a low level of CRP supports a decision to stop antibiotics after 48 hours of treatment. 193 927717_MONIC_Ch16_185-216.indd 193 6/3/13 9:34 PM Proven infections should be treated for at least 7 days, rising to 14 days in babies with S. aureus septicaemia, because of its propensity to seed to other tissues, and at least 21 days in meningitis (see below). In virtually all cases the antibiotic should be given intravenously; intramuscular antibiotics in a neonate may cause nerve and muscle damage. Oral antibiotics have no place other than in the treatment of UTI, chlamydial conjunctivitis (Table 16.1) or trivial superficial skin infections in babies who are systemically well. The choice of antibiotics in the neonatal period is becoming increasingly difficult, with the rising incidence of CONS sepsis and the emergence of multiple antibioticresistant organisms such as meticillin-resistant S. aureus, ampicillin-resistant E. coli and gentamicin-resistant gram-negative organisms. However, penicillin plus an aminoglycoside (usually gentamicin) remain the most suitable antibiotics for routine use in the neonatal period. Cephalosporins are useful second-line antibiotics, but drug resistance can rapidly emerge when they are used as first line. The suggestions in Table 16.3 may be helpful. Our current practice is to give penicillin and amikacin to babies less than 48 hours old in whom streptococci (particularly GBS) and pneumococci are a problem. Most units use gentamicin; we changed to amikacin because of a problem with gentamicin resistance. This combination provides good cover for most early-onset infections apart from S. aureus, which is not currently a major clinical problem. Beyond 48 hours we use flucloxacillin plus an aminoglycoside to cover staphylococcal disease unless the baby has a long line in situ, in which case we use teicoplanin and ceftazidime. In babies with intra-abdominal sepsis and NEC, we add metronidazole to deal with any potential anaerobic infections. Third-generation cephalosporins are very effective against most gram-negative bacilli, and they penetrate the cerebrospinal fluid (CSF) well. However, they are not effective against Streptococcus faecalis, Listeria, Enterobacter species and (with the exception of ceftazidime) Pseudomonas, and there is anxiety about their efficacy against gram-positive cocci (Goldberg 1987). Furthermore, their routine use often results in alterations in the resident flora in the unit, selecting for multiple antibioticresistant gram-negative organisms and anaerobes, such as Bacteroides. The disadvantage of using an aminoglycoside is the need to monitor plasma levels. Standard practice is to monitor the levels around the third dose, although levels should Table 16.3 Summary of suggested antibiotic regimens Choice of antibiotic Early <48 hours–1 week First line Benzyl penicillin with gentamicin or amikacin Consider amoxicillin if Listeria suspected Consider flucloxacillin if Staphylococcus aureus suspected Late >48 hours–1 week First line Flucloxacillin with gentamicin Second line Ceftazidime and teichoplanin Third line Meropenem, ciprofloxacin Meningitis First line Cefotaxime with amoxicillin or benzylpenicillin +/– gentamicin Second line Meropenem Infection Early or late infection 194 927717_MONIC_Ch16_185-216.indd 194 6/3/13 9:34 PM