Neonatology. Lesson 4. Topics:
Bacterial infections iewborns. Neonatal pneumonia.
The localized forms of infections: skin diseases, subcutaneous fat diseases, and umbilical wound infection.
Problem of the newborns’ localized purulent infection is topical question because of frequent severe consequences. This pathology is more common in premature, low weight children, newborns with birth asphyxia, birth injury. The life prognosis depends on in time diagnosis and effective treatment. That’s why doctors of different specializations have to know this pathology.
The newborn infant is more vulnerable than the older child to certain infections. The preterm baby is even less able to withstand infection and more liable to suffer serious complications.
· Humoral antibodies
o IgG is transferred across the placenta especially in the last trimester, and protects the baby against specific infections to which the mother has been immunized, e.g. measles, mumps, polio, diphtheria, tetanus, typhoid.
o This passive immunity wanes after four to six months, but may persist to 9 months e.g. measles.
o Neither IgM nor IgA cross the placenta. They are normally only produced by the infant after birth. (Note: the fetus can produce IgM in response to an intra-uterine infection e.g. congenital syphilis)
· Cell-mediated immunity:
o Lymphocytes are involved in the killing of bacteria
o The lymphocytes have not been exposed previously to antigens
· Inflammatory reaction:
o In the newborn the inflammatory response is poor and phagocytosis of bacteria by leucocytes is inefficient (due to reduced opsonins and delayed chemotaxis)
· Antenatal:
o The placenta filters out most organisms but not rubella virus, HIV, Toxoplasma, CMV and Treponema pallidum
o amniotic fluid contains lysozymes and other antibacterial agents to reduce the risk of infection
· Postnatal:
· Breast feeding:
o breast milk has IgG, IgM, IgA, macrophages and lysozymes
o lactoferrin and transferrin protect against gram negative organisms
o breast feeding promotes growth of Lactobacilli and inhibits E.coli
· Nursery care:
o Infection may be prevented by hand-washing, bathing baby and cord and eye care.
· Antenatal:
o Syphilis, HIV, rubella, CMV, varicella and bacterial chorioamnionitis
· Intranatal:
o Herpes, Streptococci, Gonococci, Candida, Chlamydia (increased risk with prolonged labour)
· Postnatal:
o Cross-infection: hands, feeds, inhalation.
· Antenatal :
o Stillbirth, fetal anomalies (e.g. rubella), congenital infections (e.g. syphilis, amniotic fluid infection syndrome with pneumonia).
· Postnatal :
o Common: conjunctivitis, oral thrush.
o Less common: cord infection, skin sepsis.
o Uncommon: urinary infection, pneumonia, septicaemia, meningitis.
· Clinical:
o superficial infection: usually obvious
o generalised infections: may present with poor feeding, lethargy, failure to gain weight, jaundice, anaemia, rash, hepatosplenomegaly, diarrhoea, vomiting, etc
o The temperature may be raised but is more ofteormal or sub-normal.
· Viral infections:
o isolate the virus, or demonstrate a rise in antibody titre
o total or specific IgM levels
o demonstrate organism, e.g. Candida, on slide using Gram stain, or culture on special agar
o obtain cultures from mother
o gastric aspirate M/C/S
o white blood count (normal 5000 to 20 000)
o immature/total neutrophil ratio (normal 0-12%)
o C reactive protein
o pus, urine, CSF, blood culture
o x-rays of chest or bones
o ECG (? myocarditis)
Scalded skin syndrome (Ritter’s disease).
Conjunctivitis. Gonococcal conjunctivitis is a serious acute inflammation which may damage the cornea leading to blindness. The onset is often rapid with red swollen mucus membranes and a copious purulent discharge. The diagnosis can be made quickly with a Gram stain on a smear of pus (Gram negative diplococci in leucocytes).
Treatment involves the instillation of Penicillin eyedrops (20,000 units/ml), frequently enough to keep eye free of pus. Repeated irrigation of the eye with saline can be used if penicillin drops are not available.
It is essential to give an additional 100,000 units of intramuscular procaine penicillin daily for 3 days in severe gonococcal conjunctivitis. Don’t forget to also treat the mother and have her VDRL checked.
Gonococcal conjunctivitis can be prevented by putting chloromycetin eye ointment into both eyes routinely after delivery.
Non-Gonococcal Conjunctivitis: Chloramphenicol ointment or drops applied 8 hourly for a week is usually sufficient for most infections aquired after delivery.
Use tetracycline or erythromycin ointment if Chlamydia infection is suspected or if inflammation recurs after chloramphenicol therapy. Proven Chlamydia infections should also be treated with oral erythromycin for 10 days.
Thrush:
Moniliasis is caused by the fungus Candida albicans and commonly affects the mouth or the nappy area. The source is usually mother’s vagina or nipples, or contaminated hands, bottles, etc.
Small white patches are found on the tongue and may spread to the inside of the cheeks and lips. These white plaques resemble curds of milk but are difficult to dislodge. The underlying mucosa is inflammed and sucking is often painful. The diagnosis is proved by the identification of spores and hyphae on microscopy. In the nappy area, the insides of skin folds (groin) are affected.
Treatment:
Mycostatin suspension (Nystatin) 1 ml (100,000 units) after each feed for 7-10 days. If mother is breast feeding, mycostatin should be applied to the nipples while vaginal infection should be eradicated. Dummies, teats and bottle must be boiled.
Skin Infections: Mostly due to Staph. aureus and may present as one or more pustules, infected vesicles, abscesses, etc. The diagnosis is made on Gram stain and culture, the results of which will determine the form of treatment. Mild superficial infection may be treated with chlorhexidine (Hibiscrub). Abscesses need incision and drainage. More severe infections, e.g. cellulitis require systemic antibiotic therapy.
Phlegmona of the newborn: local signs + expressed intoxication.
There are 4 clinical stages: incidence, alterative-necrotic, declination, reparation.
This is a local hyperemia, infiltration with distinct margins, it enlarges quickly ® infiltration became cyanotic with softening in the center ® formation of the wound surface with digger margins ® granulations, epithelization with scars formation.
Localization: chest, back, buttocks, arms and legs.
Treatment: surgical + conservative (antibiotics, desintoxication, immune therapy, symptomatic).
Mastitis of the newborn
Local signs: enlargement of the breast, condensation, local hyperthermia, hyperemia, tenderness, later – fluctuation;
Expressed intoxication (high body temperature, lost of appetite, poor sucking);
Treatment: conservative in the infiltrative stage (antibiotics), surgical in case of abscess formation).
Umbilical Infection (Omphalitis):
Causes: Omphalitis is a polymicrobial infection typically caused by a mixture of aerobic and anaerobic organisms. Associated risk factors include the following:
o Low birthweight (<
o Prior umbilical catheterization
o Septic delivery (as suggested by premature rupture of membranes, nonsterile delivery, or maternal infection)
o Prolonged rupture of membranes
Omphalitis occasionally manifests from an underlying immunologic disorder.
Rarely, an anatomic abnormality may be present, such as a patent urachus or patent omphalomesenteric duct.
Serous omphalitis: serous discharge from the umbilical stump, prolonged epithelization; symptoms from organs and systems, intoxication are absent.
Treatment: local (3% Hydrogen peroxide, Spiritus camphoratus, Viridis nitens, xerophormum).
Purulent omphalitis Local disease: Physical signs vary with the extent of disease. Signs of localized infection include the following:
o Purulent or malodorous discharge from the umbilical stump
o Periumbilical erythema
o Edema
o Tenderness
Extensive local disease: The following signs indicate more extensive local disease, such as fasciitis or myonecrosis. These signs also may suggest infection by both aerobic and anaerobic organisms and include the following:
o Periumbilical ecchymoses
o Crepitus
o Bullae
o Progression of cellulitis despite antimicrobial therapy
Fig. 1. Purulent omphalytis.
Lab Studies:
· Obtain specimens from umbilical infection routinely, and submit specimens for Gram stain and culture for aerobic and anaerobic organisms. If myonecrosis is suspected, obtain specimens from the involved muscle rather than the wound surface.
· Obtain a blood culture for aerobic and anaerobic organisms.
· Obtain a complete blood count with manual differential.
o Neutrophilia or neutropenia may be present in acute infection. An immature-to-total neutrophil ratio greater than 0.2 may be a useful indicator of systemic bacterial infection in the first few days of life.
o Thrombocytopenia may be present.
TREATMENT Medical Care: Treatment of omphalitis (periumbilical edema, erythema, and tenderness) in the newborn includes antimicrobial therapy and supportive care.
Antimicrobial therapy
o Include parenteral antimicrobial coverage for gram-positive and gram-negative organisms. A combination of an antistaphylococcal penicillin and an aminoglycoside antibiotic is recommended.
o Some believe that anaerobic coverage is important in all patients. Omphalitis complicated by necrotizing fasciitis or myonecrosis requires a more aggressive approach, with antimicrobial therapy directed at anaerobic organisms as well as gram-positive and gram-negative organisms.
§ Metronidazole may provide anaerobic coverage.
§ Clindamycin may be substituted for the antistaphylococcal penicillin.
§ As with antimicrobial therapy for other infections, consider local antibiotic susceptibility patterns.
§ Pseudomonas species have been implicated in particularly rapid or invasive disease.
o Expect erythema of the umbilical stump to improve within 12-24 hours after the initiation of antimicrobial therapy.
Supportive care: In addition to antimicrobial therapy, supportive care is essential to survival. These measures include the following:
o Provide ventilatory assistance and supplementary oxygen for hypoxemia or apnea unresponsive to stimulation.
o Administer fluid, vasoactive agents, or both for hypotension.
o Administration of platelets, fresh frozen plasma, or cryoprecipitate for DIC and clinical bleeding is suggested.
o Treat infants at centers capable of supporting cardiopulmonary function.
Management of necrotizing fasciitis and myonecrosis involves early and complete surgical debridement of the affected tissue and muscle.
Staphylococcus Aureus Infection
· Skin and soft tissue (impetigo) (Fig. 1, 2, 3, 4): Generally, this starts as a small area of erythema that progresses into bullae (filled with cloudy fluid) that rupture and heal with the formation of a crust, previously described as honey-colored. Although group A Streptococcus was considered the primary agent, S aureus has become the major pathogen since the 1980s. Bullous impetigo is caused exclusively by S aureus and is observed less frequently in the
· Initial appearance is a small area of erythema. Bullae, ie, blisterlike lesions filled with cloudy fluid, appear as the disease progresses. As bullae heal, a honey-colored crust develops.
Fig. 2. Impetigo in infant.
Fig. 3,4,5. Bullous impetigo.
· Folliculitis/furuncle/carbuncle: This is a series of progressively severe staphylococcal skin infections. Folliculitis is a tender pustule that involves the hair follicle. A furuncle involves both the skin and the subcutaneous tissues in areas with hair follicles, such as the neck, axillae, and buttocks. They actually are small abscesses characterized by exuding purulent material from a single opening. A carbuncle is an aggregate of connected furuncles and has several pustular openings. Skin infections can be self-limited, but they can also disseminate hematogenously and cause life-threatening septicemia.
Fig. 6. The superficial pustule in axillar region.
· Folliculitis is the appearance of a tender pustule involving a hair follicle. Furuncle is an apparent small abscess that exudes purulent material from a single opening. Carbuncle is an aggregate of furuncles with several openings.
· Laboratory studies: Make the diagnosis based on clinical appearance and occasionally on results of aspiration and culture of purulent material from the lesion.
· Medical Care: Impetigo/folliculitis/furuncle/carbuncle: Treatment of impetigo and other minor skin infections (ie, superficial or localized infections) can be with a topical agent such as mupirocin. Treat more extensive skin disease and bullous impetigo with oral antistaphylococcal agents.
· Scalded skin syndrome (Ritter disease (Fig. 7): A relatively rare syndrome caused by exfoliative toxin takes the form of superficial fragile blisters that burst, leaving a tender base. The patient often is febrile and occasionally has mucopurulent eye discharge. Place special emphasis in making this diagnosis because it can often be mistaken for erythema multiforme and/or toxic epidermal necrolysis, which are treated with corticosteroids. Misdiagnosis delays treatment and allows exfoliation to progress, and corticosteroid therapy could potentiate bacterial superinfection. Although the mortality rate is low in children with this entity, most fatalities are caused by delays in diagnosis.
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Fig. 7. Baby with Ritter’s disease.
· Examination shows superficial fragile blisters that burst, leaving a tender base. Skin sloughs easily when touched, called Nikolsky sign (Fig. 8). Fever is often present. A mucopurulent eye discharge may be present. As discussed above, it can often be mistaken for erythema multiforme and/or toxic epidermal necrolysis. Misdiagnosis must be avoided.
Fig. 8. Nikolsky sign.
· Therapy for this, as with any S aureus toxin–mediated disease, should be aimed at eradicating the focus of infection and ending toxin production. Administer large doses of intravenous antistaphylococcal agents, such as oxacillin (150 mg/kg/d) or a first-generation cephalosporin, such as cefazolin (100 mg/kg/d). In vitro, clindamycin has been shown to inhibit the synthesis of TSST-1, and personal experience has shown it to be extremely effective in combination with one of the above agents. Children with denuded skin should be touched as little as possible. Topical antimicrobial agents have little utility because skin damage is self-limited once systemic antibiotics are administered.
· Bone infections (osteomyelitis) Children often present with a sudden onset of fever and bony tenderness or a limp. The pain can be throbbing and quite severe; however, presentation in neonates can be quite subtle. Infants can appear well except for failure to move an extremity or pain on movement. Redness or swelling indicates that infection has spread into the subperiosteal space. Rupture of a focus of osteomyelitis into a joint space can result in septic arthritis. This is often observed in neonates.
· Bone infections are indicated by fever and bony tenderness or limp. Infants can appear well except for failure to move an extremity or pain on movement. Children with vertebral osteomyelitis present with back pain, and those younger than 3 years present with refusal to walk or with a limp. Occasionally, children with vertebral osteomyelitis may have incontinence as a presenting symptom. Children with discitis tend to present with less fever and often appear less ill than those children with vertebral osteomyelitis.
· Laboratory studies: Blood cultures are positive only in 50% of pediatric patients. Therefore, cultures of bone aspirate are useful in obtaining the organism and planning for long-term therapy. In addition, C-reactive protein or erythrocyte sedimentation rate are generally elevated in acute disease.
· Imaging Studies: On plain film radiographs, destructive bone changes are usually observed 2 weeks after infection. This is because a 30-50% reduction in bone calcium content is required before demonstration of an osteolytic lesion. Clinical diagnosis of osteomyelitis is most often supported by findings on bone scan with technetium diphosphonate. Increased tracer uptake reflects the inflammatory process in the bone lesion. However, this modality is not as useful ieonates or after trauma or surgery. MRI is the best imaging modality for defining purulent collections and for planning surgery.
· Differential diagnosis
Signs |
Osteomyelitis |
Dushen-Erb paralysis |
|
History |
Mother infections during pregnancy, delivery |
Birth trauma |
|
Time of appearing |
On the 3-5 day after birth |
From the birth |
|
Changes of the movements |
+ |
+ |
|
Intoxication |
+ |
– |
|
Local infiltration |
+ |
– |
|
Active movements in the arm |
absent |
absent |
|
Passive movements in the arm |
Very painful |
painless |
|
Blood count (leucocytosis, formula left shift) |
+ |
– |
|
Roentgenologic signes |
+ |
– |
· Therapy: Starting a semisynthetic penicillin, such as oxacillin (150 mg/kg/d), empirically is a good choice for most cases of community-acquired osteomyelitis. In patients with allergy to penicillin, a first-generation cephalosporin and lyncomycin (40 mg/kg/d) are both excellent alternatives. Cefuroxime (150 mg/kg/d) is a good alternative in younger children who are incompletely immunized because it covers H influenzae type B as well as S aureus. Only use vancomycin when the other drugs mentioned are absolutely not tolerated or when a possibility of a methicillin-resistant strain exists. The duration of therapy is a controversial topic in the literature, but the consensus among multiple authors is that the minimum effective treatment time is 4-6 weeks. A switch to oral therapy is acceptable if the child is able to take oral antibiotics, is afebrile, and if an etiologic agent is found after a good clinical response to parenteral antibiotics has been shown. Absorption of the antibiotic should be measured using serum bactericidal peaks and troughs.
· Surgical Care: Surgery is usually indicated to drain purulent material from the subperiosteal space or if infected foreign material is present.
· Septic arthritis: Typical findings include warmth, erythema, and tenderness of the joint together with constitutional symptoms and fever. An important exception to this is in infants (in whom the hip is the most commonly involved joint), where these signs may be absent. The child typically lies with the involved joint abducted and externally rotated. Because pain fibers are located within the joint capsule, movements, such as changing a diaper, that compress the head of the femur into the acetabulum cause pain. A portal of infection is almost never found, and the infection is nearly always unilateral. Patients with infection of the sacroiliac joint present with tenderness elicited during digital rectal examination and with pain during flexion, abduction, and external rotation of the hip.
· Examination shows warmth, erythema, and tenderness of the joint. Constitutional symptoms and fever are frequent. These findings may be absent in an infant. Children with infection of the sacroiliac joint present with tenderness elicited during digital rectal examination.
· Laboratory studies: Joint fluid, when obtained, is the primary means of diagnosis. The fluid should be Gram stained and cultured. In addition, the number and type of leukocytes should be determined. Median cell count in bacterial arthritis is 60.5 X 109 cells with a neutrophil predominance of greater than 75%.
· Imaging Studies: Plain radiographs show capsular swelling. They are most useful in identifying other causes of hip pain, such as Legg-Calve-Perthes disease. They should be obtained with the child in the frog leg position as well as with the legs extended and slightly internally rotated. Displacement of gluteal fat lines because of the swelling of the joint capsule is an early radiologic sign of septic arthritis. If a bone scan is performed, increased uptake on either side of the joint is visible. Pyogenic sacroiliitis is difficult to diagnose, and the radiologic method of choice is computerized tomography imaging.
· Therapy: As in osteomyelitis, start an appropriate antistaphylococcal drug (eg, oxacillin, which is penicillinase resistant; clindamycin; cefazolin) parenterally. These antibiotics reach joint fluid readily, and the concentration in the joint fluid is 30% the serum value. Therapy usually is for at least 4 weeks. Duration of parenteral therapy is often debated. Some authors have demonstrated efficacy with 1 week of parenteral therapy followed by 3 weeks of oral therapy. Make the decision to switch to oral therapy based on the ability to reliably administer a drug dosage with a peak bactericidal titer of at least 1:8. Any reaccumulation of joint fluid should be removed and cultured to assess the efficacy of therapy as well as to make the patient more comfortable.
· Surgical care: In an infant, septic arthritis of the hip and shoulder is a surgical emergency because these joints should be drained as soon as possible to prevent bony destruction. In addition, any joint should be surgically drained if a large amount of fibrin, tissue debris, or loculation is present, preventing adequate drainage by needle aspiration.
· Thrombophlebitis: Usually occurring in a hospitalized patient, the patient develops fever, pain, and sometimes erythema at the insertion site of an intravenous catheter. Occasionally, pus can be expressed. Severe suppurative thrombophlebitis can occur in burn patients, with fewer than half of diagnoses made while patients are alive.
· Patients usually have a fever and sometimes have cutaneous involvement such as erythema, induration, or tenderness. Occasionally, pus can be expressed at the insertion site of the catheter. Commonly, the exit site does not show signs of infection. Establishing infection of an intravascular device as the cause of fever in a hospitalized patient is a diagnosis of exclusion.
· Laboratory studies: Thrombophlebitis: Although management is sometimes controversial, obtaining a blood culture through the line and a peripheral blood culture is usually recommended.
· Therapy: Immediately remove the lines in any patient who is immunocompromised or severely ill. In mildly-to-moderately ill patients, a trial of antibiotic therapy, usually vancomycin and gentamicin, may be attempted. However, if the infecting organism is S aureus, such trials are usually unsuccessful.
· Surgical care: Remove the infected line in immunocompromised or severely ill patients or when infection is impossible to eradicate medically.
NECROTISING ENTEROLOCITIS Necrosis of the bowel wall may complicate bowel ischaemia after asphyxia, infection or shock iewborn infants.
Stages of the necrotizing enterocolitis
|
Stage |
Clinical signs |
X-ray |
|
І – incidence |
Bad thermoregulation, poor sucking, loss of appetite, vomiting; Local signs: meteorism, defecation up to 10 per day with large amount of mucus. |
bowel wall thickening and bubbles of air in bowel |
|
ІІ – height |
General status is hard, often apneas, bradicardia, hypotonia, lethargy; blood in stools; Local signs: vomiting is often, edema of the anterior abdominal wall, sex organs. Abdomen is enlarged, lustering, peristalsis is depressed or absent |
Enlargement bubbles of air in bowel, levels of the fluid, bubbles of air in bowel wall |
|
ІІІ – progressive |
The same + increasing of the brease and cardiac defficiency, hypothermia, jaundice, DIC-syndrome; peritonitis, bowel inpassage, ascitis |
Fluid sequestration in the abdominal cavity, bowel wall necrosis |
|
ІV – complications |
Perforation, peritonitis, anuria, DIC–syndrom, septic shock. |
The same + pneumoperitoneum |
· Complications:
o perforation, later – stenosis
· Treatment:
o nasogastric drainage
o total parenteral nutrition
o penicillin, gentamicin and metronidazole IV
o may need bowel resection
MENINGITIS Usually presents as in septicaemia. Later may show local signs e.g. full tense fontanelle, squint, convulsions, etc. Neck stiffness is unusual.
· Diagnosis:
o confirmed by lumbar puncture
· Treatment:
o suitable antibiotics given intravenously for 3 weeks e.g. Cefotaxime or Ceftriaxone or combination of ampicillin, cotrimoxazole and chloramphenicol.
URINARY TRACT INFECTION: Infection usually blood-borne. Commonest pathogen E.coli. Predisposed to by urinary tract anomalies e.g. pelvi-ureteric junction obstruction, vesico-ureteric reflux. Signs of infection are usually non-specific. The kidneys may be enlarged.
· Diagnosis:
o made by obtaining a pure growth of more than 105 orgs/ml (“clean catch” specimen), suprapubic aspiration is useful when the diagnosis is in doubt.
· Treatment:
o Cefotaxime or Ceftriaxone or an aminoglycoside. Modify once sensitivities are known.
Frequent follow-up urine examinations are advisable. An ultrasound examination and micturating cystogram should be considered at a later stage to exclude an underlying abnormality.
Prophylaxis
· Sanation and treatment of future mother
· Saving of health of healthy woman
· Hygiene of the family and sex life
In the postnatal period:
· Early breast feeding;
· Mother and her child should be together after birth;
· Natural breast feeding.
The major antibiotics active against the staphylococcal organism are presented here.
|
Drug Name |
Cephalexin (Biocef, Keflex, Keftab) |
|
Pediatric Dose |
25-100 mg/kg/d |
|
Drug Name |
Cefuroxime (Ceftin oral, Kefurox injection, Zinacef) injection |
|
Pediatric Dose |
Serious infections: 150 mg/kg/d IV divided q8h |
|
Drug Name |
Nafcillin (Nafcil injection, Nallpen injection, Unipen injection/oral) |
|
Pediatric Dose |
Neonates: |
|
Drug Name |
Cefazolin (Ancef, Kefzol, Zolicef) |
|
Pediatric Dose |
50-100 mg/kg/d IV divided q8h; not to exceed 6 g/d |
|
Drug Name |
Vancomycin (Lyphocin, Vancocin, Vancoled) |
|
Pediatric Dose |
Neonates: |
|
Drug Name |
Rifampin (Rifadin injection/oral, Rimactane oral |
|
Pediatric Dose |
S aureus: 15 mg/kg/d PO/IV divided q12h with other antibiotics |
|
Drug Name |
Mupirocin (Bactroban) — For elimination of S aureus. Inhibits bacterial growth by inhibiting RNA and protein synthesis. |
|
Adult Dose |
Apply small amount topically to affected area 2-5 times per d for 5-14 d |
|
Pediatric Dose |
Administer as in adults |
|
Contraindications |
Documented hypersensitivity; hypersensitivity to polyethylene glycol |
|
Interactions |
Concurrent intranasal administration of other medicatioot studied |
|
Pregnancy |
B – Usually safe but benefits must outweigh the risks. |
|
Precautions |
For topical use only; avoid contact with eyes; polyethylene glycol can be absorbed to toxic levels in patients with burns or open wounds; may irritate mucous membranes; overgrowth of nonsusceptible organisms can result with prolonged use |
|
Drug Name |
Amoxicillin and clavulanate (Augmentin) |
|
Pediatric Dose |
<3 months: 30 mg (based on amoxicillin component) per kg/d PO divided q12h Use 125 mg/5 mL |
|
Drug Name |
Oxacillin (Bactocill) |
|
Pediatric Dose |
Postnatal age <7 days: |
|
Drug Name |
Clindamycin (Cleocin) — Used to treat infections caused by anaerobic bacteria. |
|
Pediatric Dose |
Postnatal age <7 days: |
|
|
Other medicine to treat omphalitis |
|
Drug Name |
Metronidazole IV (Flagyl) |
|
Pediatric Dose |
Postnatal age <7 days: |
|
Drug Name |
Gentamicin (Garamycin) |
|
Pediatric Dose |
Postconception and postnatal age: |
Background: Neonatal sepsis may be categorized as early or late onset. Eighty-five percent of newborns with early-onset infection present within 24 hours, 5% present at 24-48 hours, and a smaller percentage of patients present between 48 hours and 6 days of life. Onset is most rapid in premature neonates. Early-onset sepsis syndrome is associated with acquisition of microorganisms from the mother. Transplacental infection or an ascending infection from the cervix may be caused by organisms that colonize in the mother’s genitourinary tract. The infant may acquire the microbe by passage through a colonized birth canal at delivery. The microorganisms most commonly associated with early-onset infection include group B Streptococcus (GBS), Escherichia coli, Haemophilus influenzae, and Listeria monocytogenes.
Late-onset sepsis syndrome occurs at 7-90 days of life and is acquired from the caregiving environment. Organisms that have been implicated in causing late-onset sepsis syndrome include coagulase-negative staphylococci, Staphylococcus aureus, E coli, Klebsiella, Pseudomonas, Enterobacter, Candida, GBS, Serratia, Acinetobacter, and anaerobes. The infant’s skin, respiratory tract, conjunctivae, gastrointestinal tract, and umbilicus may become colonized from the environment, leading to the possibility of late-onset sepsis from invasive microorganisms. Vectors for such colonization may include vascular or urinary catheters, other indwelling lines, or contact from caregivers with bacterial colonization.
Pneumonia is more common in early-onset sepsis, whereas meningitis and/or bacteremia are more common in late-onset sepsis. Premature and ill infants have an increased susceptibility to sepsis and subtle nonspecific initial presentations; therefore, they require much vigilance so that sepsis can be identified and treated effectively.
Pathophysiology: The infectious agents associated with neonatal sepsis have changed over the past 50 years. S aureus and E coli were the most common infectious hazards for neonates in the 1950s in the
Meningoencephalitis and neonatal sepsis syndrome can also be caused by infection with adenovirus, enterovirus, or coxsackievirus. Additionally, sexually transmitted diseases and viral diseases, such as gonorrhea, syphilis, herpes simplex virus (HSV), cytomegalovirus (CMV), hepatitis, HIV, rubella, toxoplasmosis, Trichomonas vaginalis, and Candida species, have all been implicated ieonatal infection. Bacterial organisms with increased antibiotic resistance have also emerged and have further complicated the management of neonatal sepsis. The colonization patterns iurseries and personnel are reflected in the organisms currently associated with nosocomial infection. Infants with lower birth weight and infants who are less mature in today’s neonatal intensive care units (NICUs) have increased susceptibility to these organisms.
Staphylococcus epidermidis, or coagulase-negative Staphylococcus is increasingly seen as a cause of nosocomial or late-onset sepsis, especially in the premature infant. It is considered the leading cause of late-onset infections for this population.
The neonate is unable to respond effectively to infectious hazards because of deficits in the physiological response to infectious agents.
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Fig. 7. Spread of Infection Via the Blood to the Entire Body in an Infant.
The fetus has some preimmune immunoglobulin present; however, preimmune immunoglobulin is relatively limited in fetuses compared to adults. The infant receives immunoglobulin G (IgG) prenatally after 16 weeks of gestation; however, the infant born prematurely has less IgG due to the shorter period of placental transmission of immunoglobulin.
Additionally, if the mother is immunosuppressed, it is possible that less IgG can be transmitted to the infant. The neonate is capable of synthesizing immunoglobulin M (IgM) in utero at 10 weeks of gestation; however, IgM levels are generally low at birth, unless the infant was exposed to an infectious agent during the pregnancy, thereby stimulating increased IgM production. IgG and immunoglobulin E (IgE) may be synthesized in utero; however, only traces are found in cord blood at delivery. The neonate may receive immunoglobulin A (IgA) from breastfeeding but does not secrete IgA until 2-5 weeks after birth. Response to bacterial polysaccharide antigen is diminished and remains so during the first 2 years of life.
The physical and chemical barriers to infection in the human body are present in the newborn but are functionally deficient. Skin and mucus membranes are broken down easily in the premature infant. Neonates who are ill and/or premature are additionally at risk because of the invasive procedures that breach their physical barriers to infection. Because of the interdependence of the immune response, these individual deficiencies of the various components of immune activity in the neonate conspire to create a hazardous situation for the neonate exposed to infectious threats.
Scheme of sepsis pathogenesis
pathogen, toxins, ferments
distortion of hemostasis, changes of immunogenesis
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|
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macrophages endothelial thrombocytes complement T, В–lymphocytes coagulation
cells system system
mediators of inflammation: ТNА, interleukins– IL 1,6,8, NO, prostaglandins, thromboxan А2, prostacyclin
increase of penetrate ability, vasodilatation, blood depot, hypovolemia, metabolic disorders
polyorganic insufficiency
septic shock
Mortality/Morbidity: The mortality rate ieonatal sepsis may be as high as 50% for infants who are not treated. Infection is a major cause of fatality during the first month of life, contributing to 13-15% of all neonatal deaths. Neonatal meningitis, a serious morbidity of neonatal sepsis, occurs in 2-4 cases per 10,000 live births and significantly contributes to the mortality rate ieonatal sepsis; it is responsible for 4% of all neonatal deaths.
Age: Studies have shown that premature infants have an increased incidence of sepsis. The incidence of sepsis is significantly higher in infants with very low birth weight (<
Classification of sepsis
1. Time of beginning:
· antenatal
· postnatal
o early
o late
· nosocomeal
2. Etiology: streptococcal, staphylococcal, Klebsiella’s, Escherichia’s, Candida’s, mixed etiology.
3. Clinical forms: septicemia, septicopyemia.
4. Entrance region: umbilical, pulmonary, bowel, otogenic, cryptogenic.
5. Duration:
o fulminant – few hours–1-3 days
o acute – 4-8 weeks
o prolonged – more than 8 weeks
6. Periods: initial, significant clinical signs, recovery, period of rehabilitation.
7. Complications: DIC–syndrome, thrombosis, hypotrophy, endomyocarditis, renal failure etc.
Diagnosis example: postnatal umbilical, staphylococcal sepsis, septicopyemia: (omphalitis, bilateral pneumonia with cardiovascular syndrome, respiratory failure ІІ grade, right shoulder proximal epiphysial osteomyelitis), acute duration, DIC–syndrome.
The risk factors that are associated most highly with neonatal sepsis include:
1. maternal GBS colonization (especially if untreated during labor),
2. premature rupture of membranes (PROM),
3. preterm rupture of membranes,
4. prolonged rupture of membranes,
5. prematurity,
6. and chorioamnionitis.
Predisposing risk factors also are associated with neonatal sepsis. They include:
1. maternal urinary tract infection, maternal fever greater than
2. poor maternal nutrition, low socioeconomic status,
3. poor prenatal care,
4. maternal substance abuse,
5. recurrent abortion,
6. difficult delivery,
7. low Apgar score (<6 at 1 or 5 min), birth asphyxia,
8. meconium staining,
9. low birth weight, and congenital anomalies.
An awareness of the myriad of risk factors associated with neonatal sepsis prepares the clinician for early identification and effective treatment, thereby reducing mortality and morbidity.
Physical: The clinical signs of neonatal sepsis are nonspecific and are associated with characteristics of the causative organism and the body’s response to the invasion.
· Congenital pneumonia and intrauterine infection: Inflammatory lesions are observed postmortem in the lungs of infants with congenital and intrauterine pneumonia. This may not be caused by the action of the microorganisms themselves but may be caused by aspiration of amniotic fluid containing maternal leukocytes and cellular debris. Tachypnea, irregular respirations, moderate retracting, apnea, cyanosis, and grunting may be observed. Neonates with intrauterine pneumonia may also be critically ill at birth and require high levels of ventilatory support. The chest radiograph may depict bilateral consolidation or pleural effusions.
· Congenital pneumonia and intrapartum infection: Neonates who are infected during the birth process may acquire pneumonia through aspiration of the microorganisms during the delivery process. The colonization may lead to infection with pulmonary changes, infiltration, and destruction of bronchopulmonary tissue. This damage is partly due to the granulocytes’ release of prostaglandins and leukotrienes. Fibrinous exudation into the alveoli leads to inhibition of pulmonary surfactant function and respiratory failure with an RDS-like presentation. Vascular congestion, hemorrhage, and necrosis may occur.
o Klebsiella species and S aureus are especially capable of considerably damaging the lungs, producing microabscesses and empyema.
o Infectious pneumonia is also characterized by pneumatoceles within the pulmonary tissue. Coughing, grunting, costal and sternal retractions, nasal flaring, tachypnea and/or irregular respiration, rales, decreased breath sounds, and cyanosis may be observed.
o On radiography, segmental or lobar atelectasis or a diffuse reticulogranular pattern may exist, much like what is observed in RDS.
o Pleural effusions may be observed in advanced disease.
· Congenital pneumonia and postnatal infection: Postnatally acquired pneumonia may occur at any age. Because these infectious agents exist in the environment, the likely cause depends heavily on the infant’s recent environment. If the infant has remained hospitalized in an NICU environment, especially with endotracheal intubation and mechanical ventilation, the organisms may include Staphylococcus or Pseudomonas species. Additionally, these hospital-acquired organisms frequently demonstrate multiple antibiotic resistances. Therefore, the choice of antibiotic agents in such cases requires knowledge of the likely causative organisms and the antibiotic-resistance patterns of the hospital.
· Cardiac signs: In overwhelming sepsis, an initial early phase characterized by pulmonary hypertension, decreased cardiac output, and hypoxemia is postulated to occur. These cardiopulmonary disturbances may be due to the activity of granulocyte biochemical mediators, such as hydroxyl radicals and thromboxane B2, an arachidonic acid metabolite. These biochemical agents have vasoconstrictive actions that result in pulmonary hypertension when released in pulmonary tissue. A toxin derived from the polysaccharide capsule of type III Streptococcus has also been shown to cause pulmonary hypertension. The early phase of pulmonary hypertension is followed by further progressive decreases in cardiac output with bradycardia and systemic hypotension. The infant manifests overt shock with pallor, poor capillary perfusion, and edema. These late signs of shock are indicative of severe compromise and are highly associated with mortality.
· Metabolic signs: Hypoglycemia, metabolic acidosis, and jaundice all are metabolic signs that commonly accompany neonatal sepsis syndrome. The infant has an increased glucose requirement because of sepsis. The infant may also have impaired nutrition from a diminished energy intake. Metabolic acidosis is due to a conversion to anaerobic metabolism with the production of lactic acid. When infants are hypothermic or they are not kept in a neutral thermal environment, efforts to regulate body temperature can cause metabolic acidosis. Jaundice occurs in response to decreased hepatic glucuronidation caused by both hepatic dysfunction and increased erythrocyte destruction.
· Neurologic signs: Meningitis is the common manifestation of infection of the central nervous system. It is primarily associated with GBS (36%), E coli (31%), and Listeria species (5-10%) infections, although other organisms such as S pneumoniae, S aureus, Staphylococcus epidermis, Haemophilus influenzae, and species of Pseudomonas, Klebsiella, Serratia, Enterobacter, and Proteus may cause meningitis. Acute and chronic histologic features are associated with specific organisms.
o Ventriculitis is the initiating event with inflammation of the ventricular surface. Exudative material usually appears at the choroid plexus and is external to the plexus. Then, ependymitis occurs with disruption of the ventricular lining and projections of glial tufts into the ventricular lumen. Glial bridges may develop by these tufts and cause obstruction, particularly at the aqueduct of Sylvius. The lateral ventricles may become multiloculated, which is similar to forming abscesses. Multiloculated ventricles can isolate organisms in an area, making treatment more difficult. Meningitis is likely to arise at the choroid plexus and extend via the ventricles through aqueducts into the arachnoid to affect the cerebral and cerebellar surfaces. The high glycogen content in the neonatal choroid plexus provides an excellent medium for the bacteria. Ventricular origination of meningitis causes significant treatment problems because the areas are inaccessible. Ventricular obstruction causes an additional problem.
o Arachnoiditis is the next phase and is the hallmark of meningitis. The arachnoid is infiltrated with inflammatory cells producing an exudate that is thick over the base of the brain and more uniform over the rest of the brain. Early in the infection, the exudate is primarily PMNs, bacteria, and macrophages. Exudate is prominent around the blood vessels and extends into the brain parenchyma. In the second and third weeks of infection, the proportion of PMNs decreases; the dominant cells are histiocytes, macrophages, and some lymphocytes and plasma cells. Exudate infiltration of cranial roots 3-8 occurs. After this period, the exudate decreases. Thick strands of collagen form, and arachnoid fibrosis occurs, which is responsible for obstruction. Hydrocephalus results. Early-onset GBS meningitis is characterized by much less arachnoiditis than late-onset GBS meningitis.
o Vasculitis extends the inflammation of the arachnoid and ventricles to the blood vessels surrounding the brain. Occlusion of the arteries rarely occurs; however, venous involvement is more severe. Phlebitis may be accompanied with thrombosis and complete occlusion. Multiple fibrin thrombi are especially associated with hemorrhagic infarction. This vascular involvement is apparent within the first days of meningitis and becomes more prominent during the second and third weeks.
o Cerebral edema may occur during the acute state of meningitis. The edema may be severe enough to greatly diminish the ventricular lumen. The cause is unknown, but it is likely related to vasculitis and the increased permeability of blood vessels. It may also be related to the cytotoxins of microorganisms. Herniation of edematous supratentorial structures does not occur ieonates because of the cranium’s distensibility.
o Infarction is a prominent and serious feature of neonatal meningitis. It occurs in 30% of infants who die. Lesions occur because of multiple venous occlusions, which are frequently hemorrhagic. The loci of infarcts are most often in the cerebral cortex and underlying white matter but may also be subependymal within the deep white matter. Neuronal loss occurs, especially in the cerebral cortex, and periventricular leukomalacia may subsequently appear in areas of neuronal cell death.
o Meningitis due to early-onset neonatal sepsis usually occurs within 24-48 hours and is dominated by nonneural signs. Neurologic signs may include stupor and irritability. Overt signs of meningitis occur in only 30% of cases. Even culture-proven meningitis may not demonstrate white cell changes in the CSF. Meningitis due to late-onset disease is more likely to demonstrate neurologic signs (80-90%). Impairment of consciousness (ie, stupor with or without irritability), coma, seizures, bulging anterior fontanel, extensor rigidity, focal cerebral signs, cranial nerve signs, and nuchal rigidity occur.
o The CSF findings in infectious neonatal meningitis are an elevated WBC count (predominately PMNs), an elevated protein level, a decreased CSF glucose concentration, and positive cultures. The decrease in CSF glucose concentration does not necessarily reflect serum hypoglycemia. Glucose concentration abnormalities are more severe in late-onset disease and with gram-negative organisms. The CSF WBC count is within the reference range in 29% of GBS meningitis infections; in gram-negative meningitis, it is within the reference range in only 4%. Reference range CSF protein and glucose concentrations are found in about 50% of patients with GBS meningitis; however, in gram-negative infections, reference range CSF protein and glucose concentrations are found in only 15-20%.
o Temperature instability is observed with neonatal sepsis and meningitis, either in response to pyrogens secreted by the bacterial organisms or from sympathetic nervous system instability. The neonate is most likely to be hypothermic. The infant is also floppy, lethargic, and disinterested in feeding. Signs of neurologic hyperactivity are more likely when late-onset meningitis occurs.
· Hematologic signs
o The platelet count in the healthy newborn is rarely less than 100,000 per mm3 in the first 10 days of life. Thrombocytopenia with counts less than 100,000 may occur in neonatal sepsis in response to the cellular products of the microorganisms. These cellular products cause platelet clumping and adherence leading to platelet destruction. Thrombocytopenia is generally observed after sepsis has been diagnosed and usually lasts 1 week, though it can last as long as 3 weeks. Only 10-60% of infants with sepsis have thrombocytopenia. Because of the appearance of newly formed platelets, mean platelet volume (MPV) and platelet distribution width (PDW) are shown to be significantly higher ieonatal sepsis after 3 days. Because of the myriad of causes of thrombocytopenia and its late appearance ieonatal sepsis, the presence of thrombocytopenia does not aid the diagnosis of neonatal sepsis.
o WBC counts and ratios are more sensitive for determining sepsis than platelet counts, although normal WBC counts may be observed in as many as 50% of cases of culture-proven sepsis. Infants who are not infected may also demonstrate abnormal WBC counts related to the stress of delivery. A differential may be of more use in diagnosing sepsis. Total neutrophil count (PMNs and immature forms) is slightly more sensitive in determining sepsis than total leukocyte count (percent lymphocyte + monocyte/PMNs + bands). Abnormal neutrophil counts, taken at the time of symptom onset, are only observed in two thirds of infants; therefore, the neutrophil count does not provide adequate confirmation of sepsis. Neutropenia is observed with maternal hypertension, severe perinatal asphyxia, and periventricular or intraventricular hemorrhage.
o Neutrophil ratios have been more useful in diagnosing or excluding neonatal sepsis; the immature-to-total (I/T) ratio is the most sensitive. All immature neutrophil forms are counted, and the maximum acceptable ratio for excluding sepsis during the first 24 hours is 0.16. In most newborns, the ratio falls to 0.12 within 60 hours of life. The sensitivity of the I/T ratio has ranged from 60-90%, and elevations may be observed with other physiological events; therefore, when diagnosing sepsis, the elevated I/T ratio should be used in combination with other signs.
· Gastrointestinal signs: The gut can be colonized by organisms in utero or at delivery by swallowing infected amniotic fluid. The immunologic defenses of the gut are not mature, especially in the preterm infant. Lymphocytes proliferate in the gut in response to mitogen stimulation; however, this proliferation is not fully effective in responding to a microorganism because antibody formation and cytokine formation is immature until approximately 46 weeks. Necrotizing enterocolitis (NEC) has been associated with the presence of a number of species of bacteria in the immature gut, and bacterial overgrowth of these organisms in the neonatal lumen is a component of the multifactorial pathophysiology of NEC.
Lab Studies:
Blood, CSF, and urine cultures
· Aerobic cultures are appropriate for most of the bacterial etiologies associated with neonatal sepsis; however, anaerobic cultures are indicated ieonates with abscess formation, processes with bowel involvement, massive hemolysis, and refractory pneumonia.
· A Gram stain provides early identification of the gram-negative or gram-positive status of the organism for preliminary identification.
· Bacterial cultures should generally reveal the organism of infection within 36-48 hours; the subsequent initial identification of the organism occurs within 12-24 hours of the growth.
· Urine cultures are most appropriate when investigating late-onset sepsis.
· Blood and CSF cultures are appropriate for early and late-onset sepsis.
· Because of the low incidence of meningitis in the newborn infant with negative cultures, clinicians may elect to culture the CSF of only those infants with documented or presumed sepsis.
A CBC and differential may be ordered serially to determine changes associated with the infection, such as thrombocytopenia or neutropenia, or to monitor the development of a left shift or an elevated I/T ratio. Such serial monitoring of the CBC may be useful in aiding the differentiation of sepsis syndrome from nonspecific abnormalities due to the stress of delivery.
· The platelet count in the healthy newborn is rarely less than 100,000 per mm3 in the first 10 days of life. Thrombocytopenia with counts less than 100,000 may occur in neonatal sepsis, although this sign is usually observed late in the infection. MPV and PDW have been shown to be significantly elevated in infants with sepsis after 2-3 days of life. These measures may assist in determining the etiology of thrombocytopenia.
· WBC counts and ratios are more sensitive in determining sepsis, although normal WBC counts may be observed in culture-proven sepsis in as many as 50% of cases. Infants who are not infected may also have abnormal WBC counts related to the stress of delivery. A differential may be of more use in diagnosing sepsis. Total neutrophil count (PMNs and immature forms) is slightly more sensitive in determining sepsis than total leukocyte count (percent lymphocyte + monocyte/PMNs + bands). Abnormal neutrophil counts at the time of symptom onset are only observed in two thirds of infants; therefore, neutrophil count does not provide adequate confirmation of sepsis. Neutropenia is also observed with maternal hypertension, severe perinatal asphyxia, and periventricular or intraventricular hemorrhage.
· Neutrophil ratios have been more useful in diagnosing neonatal sepsis; the I/T ratio is the most sensitive. All immature neutrophil forms are counted, and the maximum acceptable ratio for excluding sepsis in the first 24 hours is 0.16. In most newborns, the ratio falls to 0.12 within 60 hours of life. The sensitivity of the I/T ratio has ranged from 60-90%, and elevations may be observed with other physiological events; therefore, when diagnosing sepsis, the elevated I/T ratio should be used in combination with other signs.
The CSF findings in infectious neonatal meningitis are an elevated WBC (predominately PMNs), an elevated protein level, a depressed glucose level, and positive cultures. The decrease in glucose is not reflective of serum hypoglycemia. The CSF abnormalities are more severe in late onset and with gram-negative organisms. The WBC is within the reference range in 29% of GBS meningitis infections; in gram-negative meningitis, it is within the reference range in only 4%. Reference range protein and glucose concentrations are found in about 50% of patients with GBS meningitis; however, in gram-negative infections, reference range protein and glucose concentration are found in only 15-20%.
C-reactive protein, an acute phase protein associated with tissue injury, is eventually elevated in 50-90% of infants with systemic bacterial infections. This is especially true of infections with abscesses or cellulitis of deep tissue. C-reactive protein usually rises within 24 hours of infection, peaks within 2-3 days, and remains elevated until the inflammation is resolved. The C-reactive protein level is not recommended as a sole indicator of neonatal sepsis, but it may be used as part of a sepsis workup or as a serial study during infection to determine response to antibiotics, duration of therapy, and/or relapse of infection.
IgM concentration in serum may be helpful in determining the presence of an intrauterine infection, especially if present over a period of time.
Imaging Studies:
· Chest radiographs may depict segmental or lobar atelectasis, but they more commonly reveal a diffuse, fine, reticulogranular pattern, much like what is observed in RDS. Hemothorax and pleural effusions may also be observed.
·
scan may be needed late in the course of complex neonatal meningitis to document any occurrence of blocks to CSF flow, the site where the blocks are occurring, and occurrence of major infarctions or abscesses. Signs of chronic stage disease, such as ventricular dilation, multicystic encephalomalacia, and atrophy, are also demonstrated on CT scan.
· Head ultrasonograms ieonates with meningitis show evidence of ventriculitis, abnormal parenchymal echogenicities, extracellular fluid, and chronic changes. Serially, head ultrasonograms can demonstrate the progression of complications.
Procedures: Lumbar puncture is warranted for early- and late-onset sepsis, although clinicians may be unsuccessful in obtaining sufficient or clear fluid for all the studies. Infants may be positioned on their side or sitting with support, but adequate restraint is needed to avoid a traumatic tap. Because the cord is lower in the spinal column in infants, the insertion site should be between L3 and L4. If positive cultures are demonstrated, a follow-up lumbar puncture is often performed within 24-36 hours after antibiotic therapy to document CSF sterility. If organisms are still present, modification of drug type or dosage may be required to adequately treat the meningitis. An additional lumbar puncture within 24-36 hours is necessary if organisms are still present.
Complications
1. Septic shock is sepsis with uncorrected hypotension, hypoperfusion of tissues, acidosis, oliguria, conscious changes.
o Early septic shock is sepsis with hypotension, hypoperfusion of capillaries; which may be corrected in the short period of time by fluids or/and medicine.
o Refractive septic shock is sepsis with hypotension, hypoperfusion of capillaries; which is not corrected by fluids or/and medicine more than 1 hour; need dopamine, adrenalin or noradrenalin correction.
Septic shock’s stages: І – decreasing of blood circulation; ІІ – early decompensation; ІІІ – late decompensation; IV – irreversible (agonizing).
2. DIC–syndrome, stages: І – hypercoagulation; ІІ – hypocoagulation; ІІІ – consume coagulopathy; IV – restoring.
DIFFERENTIALS These nonspecific clinical signs of early sepsis syndrome are also associated with other neonatal diseases, such as Respiratory Distress Syndrome (RDS), metabolic disorders, intracranial hemorrhage, and a traumatic delivery. Therefore, diagnose neonatal sepsis by excluding other disease processes, performing an examination, and testing for more specific indications of neonatal sepsis.
|
Criteria
|
Meningitis
|
Localized forms of infection
|
Congenital infections
|
Birth trauma |
|
1. Anamnesis:
|
|
|
|
|
|
Acute and chronic maternal diseases during the pregnancy
|
+
|
––
|
+ |
––
|
|
Mastitis during breastfeeding period
|
+
|
––
|
–– |
––
|
|
Umbilical late epithelization |
+
|
+
|
–– |
––
|
|
Purulent changes of the skin
|
+
|
+
|
–– |
––
|
|
Rapid delivery
|
–– |
–– |
–– |
+ |
|
Complicated delivery of shoulders
|
––
|
––
|
–– |
+
|
|
Using of forceps, vacuum extraction |
–– |
–– |
––– |
+ |
|
2.Prolonged intoxication:
|
+
|
––
|
+ |
––
|
|
-increased body temperature
|
+
|
––
|
–– |
––
|
|
–loss of appetite
|
+
|
+
|
+ |
+
|
|
–vomiting,
|
+
|
–
|
+ |
+
|
|
–skin color:
|
|
|
|
|
|
–pale-pink
|
––
|
+
|
–– |
–– |
|
–pallor
|
+ |
––
|
–– |
+
|
|
–pale-grey
|
+ |
––
|
+ |
––
|
|
–yellow |
+ |
–– |
+ |
+ |
|
–weight gain: –slow
|
–– |
+ |
–– |
+
|
|
–absent
|
+ – |
––
|
+ |
––
|
|
– jaundice:
|
+
|
––
|
+ |
+
|
|
–conjugated
|
–– |
–– |
–– |
+ |
|
–parenchimatous |
+ |
–– |
+ |
–– |
|
З.Presence of hematogenous methastatic sites of infection
|
+
|
––
|
+ |
––
|
|
–hepatosplenomegaly
|
+
|
––
|
+ |
––
|
|
4.Positive cultures
|
|
|
|
|
|
–blood
|
+
|
––
|
+ |
––
|
|
–from sites of infection |
+
|
+
|
+ |
––
|
|
5. CSF: |
|
|
|
|
|
– transparent
|
––
|
+
|
–– |
––
|
|
–muddy – hemorrhagic – pleocytosis – proteinorrhachia 6. Disappearance of the clinical signs during treatment: – slow – rapid – absent |
+ –– ++ +
+ –– –– –– |
–– –– –– ––
–– + –– ––
|
+ –– + +
+ –– + + |
–– + –– ––
+ –– –– –– |
TREATMENT Medical Care: Initiate treatment immediately because of the neonate’s immunologic weaknesses for fighting infection. Begin antibiotics as soon as diagnostic tests are performed. Additional therapies have been investigated for the treatment of neonatal sepsis; however, no unequivocal proof that these treatments are beneficial exists. These additional therapies include granulocyte transfusion, intravenous immune globulin (IVIG) replacement, exchange transfusion, and the use of recombinant cytokines.
Antibiotic therapy In the
· If infection appears to be nosocomial, direct coverage at organisms implicated in hospital-acquired infections, including S aureus, S epidermis, and Pseudomonas species. Most strains of S aureus produce beta-lactamase, which makes them resistant to penicillin G, ampicillin, carbenicillin, and ticarcillin. Vancomycin has been favored for this coverage; however, concern exists that overuse of this drug may lead to vancomycin-resistant organisms, thereby eliminating the best response to these resistant organisms. Cephalosporins are attractive in the treatment of nosocomial infection because of their lack of dose-related toxicity and adequate serum and CSF concentration; however, resistance by gram-negative organisms has occurred with their use. Do not use ceftriaxone in infants with hyperbilirubinemia because it displaces bilirubin from serum albumen. Resistance and sensitivities for the organism are used to indicate the most effective drug.
· Aminoglycosides and vancomycin are both ototoxic and nephrotoxic; have caution when using them. Check the serum level after 48 hours of treatment to determine if levels are above those required for a therapeutic effect. The dosage amount or interval may need to be changed to ensure adequate but nontoxic coverage. A serum level may be warranted when the infant’s clinical condition has not improved to ensure that a therapeutic level has been reached. In addition, perform renal function and hearing screening to determine any short- or long-range toxic effects of these drugs.
· If cultures are negative but the infant has significant risk for sepsis and/or clinical signs, the clinician must decide whether to provide continued treatment. Three days of negative cultures should provide confidence in the data; however, a small number of infants with proven sepsis at postmortem had negative cultures during their initial sepsis workup. Management is further complicated if the mother received antibiotic therapy before delivery, especially close to delivery. This may result iegative cultures in the infant who is still ill. Review all diagnostic data, including cultures, maternal and intrapartal risk factors, CSF results, the CBC and differential radiographs, and the clinical picture to determine the need for continued therapy. Treatment for 7-10 days may be appropriate, even if the infant has negative cultures at 48 hours.
· The clinician may require different antibiotic choice, dosage, and/or treatment time if the infant has bacterial meningitis. Perform a follow-up lumbar puncture within 24-36 hours after antibiotic therapy has been initiated to determine if the CSF is sterile. If organisms are still present, modification of drug type or dosage is required to adequately treat the meningitis. Continue antibiotic treatment for 2 weeks after sterilization of the CSF or for a minimum of 2 weeks for gram-positive meningitis and 3 weeks for gram-negative meningitis, whichever period is longest. Chloramphenicol or trimethoprim-sulfamethoxazole has been shown to be effective in the treatment of highly resistant bacterial meningitis.
Granulocyte transfusion has been shown to be suitable for infants with significant depletion of the storage neutrophil pool; however, the documentation of storage pool depletion requires a bone marrow aspiration, and the granulocyte transfusion must be administered quickly to be beneficial. The number of potential adverse effects, such as graft versus host reaction, transmission of CMV or hepatitis B, and pulmonary leukocyte sequestration, is considerable. Therefore, this therapy remains an experimental treatment.
Intravenous immune globuline has been considered for neonatal sepsis to provide type-specific antibodies to improve opsonization and phagocytosis of bacterial organisms and to improve complement activation and chemotaxis of neonatal neutrophils; however, difficulties with IVIG therapy for neonatal sepsis exist. The effect has been transient, and adverse effects associated with the infusion of any blood product can occur. Dose-related problems with this therapy decrease its usefulness ieonatal populations.
Recombinant human cytokine administration to stimulate granulocyte progenitor cells has been studied as an adjunct to antibiotic therapy. These therapies have shown promise in animal models, especially for GBS sepsis, but require pretreatment or immediate treatment to demonstrate efficacy. The use of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) has been studied in clinical trials, but their use in clinical neonatology remains experimental.
The infant with sepsis may require treatment aimed at the overwhelming systemic effects of the disease. Cardiopulmonary support and intravenous nutrition may be required during the acute phase of the illness until the infant’s condition stabilizes. Monitoring of blood pressure, vital signs, hematocrit, and platelets is vital.
Surgical Care: If hydrocephalus associated with neonatal meningitis occurs, and progressive accumulation of CSF is present, placing a ventriculoperitoneal (VP) shunt may be necessary to drain off the excess fluid. The immediate complications of shunt placement are overdrainage, equipment failure, disconnection, migration of catheter, or shunt infection. Abdominal obstruction, omental cysts, and perforation of the bladder, gall bladder, or bowel occur infrequently. The VP shunt may cause long-term neurologic complications, including slit-ventricle syndrome, seizures, neuro-ophthalmological problems, and craniosynostosis; however, the outcome for children with VP shunt placement is generally good with careful follow-up.
Diet: The neonate may need to be giveothing by mouth (NPO) during the first days of treatment because of gastrointestinal symptoms or poor feeding. Consider parenteral nutrition to ensure that the patient’s intake of calories, protein, minerals, and electrolytes is adequate during this period. Feeding may be restarted via a nasogastric tube for the infant with serious compromise. Encourage that breast milk be given because of the immunologic protection it provides.
Activity: The infant with temperature instability needs thermoregulatory support with a radiant warmer or incubator. Also, encouraging parental contact is important to ease the stress for parents and continue the bonding between the parents and child.
|
Drug Name |
Ampicillin (Marcillin, Omnipen, Polycillin, Principen, Totacillin) |
|
Pediatric Dose |
<7 days and <2000 g: 50 mg/kg/dose IV/IM q12h |
|
Drug Name |
Gentamicin (Garamycin) |
|
Pediatric Dose |
0-4 weeks and <1200 g: 2.5 mg/kg/dose IV/IM q18h |
|
Drug Name |
Cefotaxime (Claforan) |
|
Pediatric Dose |
<7 days: 50 mg/kg/dose IV/IM q12h |
|
Drug Name |
Vancomycin (Lyphocin, Vancocin, Vancoled) — |
|
Pediatric Dose |
<1 month: |
|
Drug Name |
Metronidazole (Flagyl) — Antimicrobial that has shown effectiveness against anaerobic infections, especially Bacteroides fragilis meningitis. |
|
Pediatric Dose |
<4 weeks and <1200 g: 7.5 mg/kg/dose PO/IV q2d |
|
Drug Name |
Erythromycin (E-Mycin, Erythrocin) –. |
|
Pediatric Dose |
<7 days and <2000 g: 5 mg/kg/dose PO/IV/IM q12h |
|
Drug Name |
Piperacillin (Pipracil) |
|
Pediatric Dose |
<7 days and 1200-2000 g: 75 mg/kg IV/IM q12h |
Drug Category: Antifungals — Fungal infections can masquerade as bacterial infections and/or may appear at the end of prolonged antibacterial therapy.
|
Drug Name |
Fluconazole (Diflucan) — Used to treat susceptible fungal infections, including oropharyngeal, esophageal, and vaginal candidiasis. Also used for systemic candidal infections and cryptococcal meningitis. |
|
Pediatric Dose |
0-14 days: Oropharyngeal candidiasis: 6 mg/kg PO/IV initial dose; after 3 d, 3 mg/kg q3d for a total of 14 d |
|
Drug Name |
Amphotericin B (Amphocin, Fungizone) |
|
Pediatric Dose |
Test dose: 0.1 mg/kg/dose IV; not to exceed 1 mg/dose infused over 20-60 min or 0.25 mg/kg infused over 6 h; if tolerated, administer 0.25 mg/kg/d; gradually increase dose by 0.25-mg/kg/d increments until desired daily dose reached |
Deterrence/Prevention: The Committee on Infectious Diseases of the AAP recommends that obstetric care include a strategy to manage early-onset GBS disease. Treat women with GBS bacteriuria during pregnancy when it is diagnosed and at delivery. The committee also recommends that women who have previously given birth to an infant with GBS disease be intrapartally treated. Practitioners should use either a strategy based on screening the mother or a strategy based on the presence of intrapartum risk factors to minimize the risk of early-onset GBS disease.
Prognosis: With early diagnosis and treatment, infants are not likely to experience long-term health problems associated with neonatal sepsis; however, if early signs and/or risk factors are missed, the mortality rate increases. Residual neurologic damage occurs in 15-30% of neonates with septic meningitis. Infants with meningitis may acquire hydrocephalus and/or periventricular leucomalacia. They may also have complications associated with the use of aminoglycosides, such as hearing loss and/or nephrotoxicity.
