- Author: Michael P Sherman, MD, FAAP; Chief Editor: Ted Rosenkrantz, MD more...
Early delivery, supportive care, and antibiotic administration for the mother with chorioamnionitis are discussed in Medical Care. The antibiotics used most often to treat mothers with acute chorioamnionitis are also discussed.
The treatment of bacterial vaginosis has also been discussed above; however, antibiotic therapy for this condition is often not successful.[189, 190]
The treatment of the potentially septic neonate is complex. An overview of the treatment for early-onset neonatal infection is summarized in Medical Care.
Maternal antibiotics for chorioamnionitis
The standard drug treatment in the mother with chorioamnionitis includes ampicillin and an aminoglycoside (ie, usually gentamicin), although clindamycin may be added for anaerobic pathogens. Clindamycin may also be used if the mother is allergic to penicillin, although some experts propose use of a cephalosporin. In cases involving premature labor or premature, pre-labor rupture of membranes, penicillin or ampicillin is frequently administered as a chemotherapeutic agent to prevent group B streptococcal (GBS) colonization of the fetus. The use of penicillin alone is suggested for GBS chemoprophylaxis during the intrapartum period. Using penicillin rather than ampicillin may avoid colonization of the fetus with ampicillin-resistant E coli. The rationale for ampicillin use when maternal chorioamnionitis is suspected is that ampicillin would treat GBS, Haemophilus species, many enterococci strains, and Lmonocytogenes.
For more information on intrapartum antibiotic use to prevent GBS, see the Medscape Reference topic Bacterial Infections and Pregnancy.
Clindamycin may treat S aureus and anaerobes. Gentamicin provides broad-spectrum coverage against gram-negative bacteria. These antibiotics should be given intravenously. The drugs mentioned above are generally safe for mother and fetus. An absolute contraindication to use of these antibiotics is a known allergic reaction to them. Renal function must always be considered when using antibiotics, especially aminoglycosides.
If a urinary tract infection is present, the appropriate antibiotic or combination of antibiotics should be used to treat the specific bacterium isolated from the urine.
Erythromycin is infrequently used in women allergic to penicillin. Its ability to enter urogenital secretions has been questioned, especially in the treatment of Ureaplasma urealyticum -related or Mycoplasma hominis -related colonization in pregnant women. An effective treatment of Ureaplasma or Mycoplasma infections in mothers or their infants is needed because these potential pathogens cause substantial morbidity and even mortality in the preterm neonate.[62, 191]
Of the invasive GBS strains that were isolated in one study, resistance to either clindamycin or erythromycin was in excess of 20%, whereas colonizing isolates of GBS had resistance in more than 40% of cases. A report from the CDC noted that, of 4882 isolates of GBS, 15% and 32% were resistant to clindamycin and erythromycin, respectively. This suggests that erythromycin or clindamycin used as chemoprophylaxis to prevent GBS infection in neonates is problematic in women with penicillin allergy.
Dosages of antibiotics to treat maternal chorioamnionitis are not provided because this is a pediatric review addressing maternal chorioamnionitis as it affects the newborn infant.
Supportive, immune, and antibiotic therapy of early onset bacterial infection
An extensive discussion of the management of septic neonates is not possible in this article but is available in other Medscape Reference chapters (see Neonatal Sepsis). Critical points to ensure intact survival of the neonate are mentioned for completeness. For example, ventilator management and surfactant replacement therapy can be used to treat the neonate with congenital bacterial pneumonia, but a complete discussion of the techniques involved in this therapy are covered in other articles. Physicians and nurses attending the delivery of a newborn whose mother is suspected of having chorioamnionitis should be ready to perform a full resuscitation, including intubation, providing positive-pressure ventilation, and treatment of hypovolemia, shock, and respiratory and/or metabolic acidosis. Low Apgar scores may be another indicator of sepsis.
After initial stabilization of a neonate with potential infection in the delivery room, attention is directed toward the following variables that influence survival:
Warmth, monitoring of vital signs, and maintenance of fluid, electrolyte balance, and correction of significant metabolic acidosis
Management of the circulation, including correction of hypovolemia and enhancement of cardiac performance with inotropic drugs if sepsis-related myocardial dysfunction is noted
Treatment of respiratory distress that may entail surfactant replacement (for pneumonia, respiratory distress syndrome) and different modes of assisted ventilation (Inhaled nitric oxide may be considered as a therapy in the presence of pulmonary hypertension.)
Assessment and treatment of thrombocytopenia and coagulopathy, if present
The aforementioned elements of supportive care are essential to reducing morbidity and mortality. When myocardial dysfunction, cardiovascular collapse, and severe pulmonary hypertension are not reversible, extracorporeal membrane oxygenation (ECMO) may be a life-saving intervention. In critically-ill septic neonates that are near-term or term, the importance of early referral for ECMO cannot be overstated.
Pulmonary hypertension can complicate the management of neonatal sepsis, and inhaled nitric oxide may reverse this complication. The use of inhaled nitric oxide in a non-ECMO facility may be problematic. This is particularly true if the septic neonate deteriorates and must be transferred to an ECMO facility while on inhaled nitric oxide therapy. The referring facility may not have the capability to provide inhaled nitric oxide during transport to the ECMO facility. In this circumstance, the seriously-ill infant may become critically ill with the cessation of inhaled nitric oxide therapy during transport. Therefore, guidelines for referral to an ECMO center should be established for each neonatal ICU (NICU) based on the center's own resources and ability to safely transport such infants.
Guidelines for immunotherapy in early onset sepsis (EOS) are not well established. Treatments used include administration of granulocyte or granulocyte-macrophage colony-stimulating factors (eg, filgrastim, sargramostim); intravenous administration of immunoglobulin G (IgG), particularly if a high-titer IgG antibody is specifically directed against the bacterial pathogen; and leukocyte transfusions for depletion of neutrophils in the bone marrow storage pool. Despite research on each of these immunotherapies, no agreement regarding their use has been reached. A neonatologist, pediatric infectious disease subspecialist, or both should be consulted if immunotherapy is contemplated.
Antibiotic therapy for early onset bacterial infection of the neonate usually includes the administration of a penicillin (ie, ampicillin is most often used for additional coverage against Haemophilus species, enterococci, and listeriosis) and an aminoglycoside (ie, usually gentamicin). Generally, gentamicin provides ample coverage against gram-negative bacteria that cause EOS. The third-generation cephalosporins should be used as part of the antibiotic regimen if resistant E coli is suspected based on maternal history, amniotic fluid cultures, and the clinical picture. Cefotaxime has been advocated by experts when meningitis is suspected or when an asphyxiated infant or an extremely preterm infant is being treated and severe renal dysfunction may occur.
Antibiotic administration in newborns is based on birth weight criteria and gestational age at birth. Doses of antibiotics change as postnatal age increase and renal function improves. Administration of aminoglycosides should include changes in dosing based on pharmacokinetics.
Final decisions about antibiotics should be based on positive culture results from appropriate anatomic sites. If renal dysfunction is present, antibiotic dosages should be adjusted during the course of their administration. This is particularly true for aminoglycoside administration in extremely premature newborns and in newborns with urogenital anomalies.
Recommendations on the appropriate antibiotic dose can be found in soft-cover neonatology textbooks (ie, Neonatology: Management, Procedures, On-Call Problems, Diseases, and Drugsor Manual of Neonatal Care) and classic textbooks of neonatal-perinatal medicine. Specific textbooks about antibiotic use in pediatric patients, including neonates (ie, Nelson's Pocketbook of Pediatric Antimicrobial Therapy), have also been written. For this article, the NEOFAX 2009 was used for selecting the dose per kilogram and the dosing interval for specific antibiotics. The review on antibiotics to treat EOS is not exhaustive.
Lastly, the physician must consider the duration of antibiotic therapy. This is particularly true when deciding the duration of antibiotic treatment for well-appearing term neonates. In the era of managed care, in which cost reductions are typical, discontinuing antibiotics in healthy term neonates within 24-48 hours of initiating therapy is probably safe. With current bacteriologic techniques, more than 90-95% of neonatal blood cultures become positive within 48 hours of the time they are cultivated. A negative C-reactive protein (CRP) result when reviewed at 48 hours after birth suggests antibiotic treatment can be stopped.
In neonates with proven infection, the well-being of the infected newborn should guide the duration of antibiotic therapy. The bacterium causing the infection and the site of the infection also influence the duration of antibiotic therapy. For example, bacterial pneumonia is often treated for 7-10 days with antibiotics. Bacteremia is often treated with antibiotics for 10-14 days. This duration is based on the potential for recurrence with shorter courses of treatment (ie, 10 days of antibiotics is often considered a minimum for GBS-associated bacteremia).
Cerebrospinal fluid (CSF) infections may require antibiotic therapy for 2-4 weeks based on the bacterium responsible for the infection, findings on an analysis of CSF indicating the resolution of infection, and the presence of complications associated with meningitis. For uncomplicated GBS-related infections of the CSF, 2 weeks may be sufficient; other gram-positive and all gram-negative bacteria often require 3-4 weeks of antibiotic therapy. Surgical interventions for localized CNS infections (eg, an infectious epidural collection, brain abscess) or the presence of post-infectious hydrocephalus may indicate antibiotic therapy needs to be provided for as long as 4-6 weeks.
The following information reviews the antibiotics that are commonly used to treat early-onset bacterial infections in the neonate. The antibiotics covered are not exhaustive. For example, the use of azithromycin to treat congenital pneumonia caused by Urealyticum or Mycoplasma is not reviewed. A report that used azithromycin to treat pregnant women revealed this antibiotic was less effective compared with other antimicrobials. Issues related to infections caused by these microbes and other special bacteria in neonates may require consultation with a neonatologist or a pediatric infectious diseases subspecialist.
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the clinical setting. Antibiotic combinations are usually recommended for serious Gram-negative bacillary infections. This approach ensures coverage for a broad range of organisms and polymicrobial infections. In addition, it prevents resistance in bacterial subpopulations and provides additive or synergistic effects. Once organisms and sensitivities are known, the use of antibiotic monotherapy is then recommended. The exception would be bacteria that could attain a highly-resistant plasmid against antimicrobials. Information about antimicrobials used to treat neonates and the source for this review is NEOFAX2009.
Aqueous crystalline penicillin G is considered the first-line agent for GBS. Ampicillin may be used, however, recent concern surrounds ampicillin-resistant E coli infections. Other modified penicillins such as oxacillin or nafcillin (antistaphylococcal), netilmicin (antipseudomonal or other Gram-negative enteric bacteria), and piperacillin (antipseudomonal) are not typically used as first-line antibiotics for treatment of early-onset neonatal infections. The aforementioned modified penicillins are designed to treat infections caused by penicillin-resistant bacteria that can express beta-lactamase. These modified penicillins are usually reserved for the treatment of postnatally acquired infections in hospitalized neonates. Methicillin-resistant staphylococcal infections have emerged in pregnant women, and neonates with EOS who have these staphylococci are reported; such infections require treatment with vancomycin.
Aqueous crystalline penicillin G (pen G) administered IV is the DOC for GBS bacteremia or meningitis. Pen G is also known as benzylpenicillin. Do not confuse pen G with benzathine or procaine penicillin used only for IM injections; pen G is the original antibiotic in the penicillin class and inhibits synthesis of the bacterial cell wall. Pen G may provide adequate coverage for S pneumoniae when it is a cause of early onset bacterial infection in neonates (infrequent) but this bacterium can also have resistance to pen G.
A more broad-spectrum aminopenicillin used for many years as either a definitive or a prophylactic therapy for early-onset bacterial infection of neonates (ie, GBS and susceptible E coli). May provide additional coverage against Haemophilus species, many enterococci, other streptococci, Listeria monocytogenes, and a limited number of susceptible gram-negative enteric bacteria. Indicated for neonatal bacteremia or meningitis due to GBS.
A third-generation cephalosporin with enhanced potency against many gram-negative bacteria. Generally considered inactive against enterococci, Listeria, and most strains of pseudomonads and bacteroides. Some experts consider this antibiotic the preferred therapy for neonatal meningitis caused by gram-negative bacteria if the bacterium is sensitive to it (and in conjunction with an aminoglycoside). This preference is based on more effective CNS penetration of cefotaxime. Indicated when aminoglycosides may be contraindicated (eg, significant renal failure) or when aminoglycosides may have enhanced toxicity.
Gentamicin is one of the aminoglycoside antibiotics (ie, amikacin, netilmicin, and tobramycin). Generally, gentamicin has activity against Pseudomonas aeruginosa, whereas kanamycin does not. First choice for prophylactic or definitive therapy of early-onset bacterial infections in neonates because it has broad activity against many gram-negative bacilli. Amikacin and tobramycin are usually reserved to treat nosocomial infections caused by gram-negative bacteria that are resistant to gentamicin.
Aminoglycosides should not be used alone to treat infections potentially caused by gram-positive bacteria. Thus, a penicillin is always included in the treatment of early-onset bacterial infections in neonates. Furthermore, to prevent the emergence of highly antibiotic-resistant gram-negative bacteria, nosocomial infections in hospitalized neonates should never be treated with an aminoglycoside alone. A second antibiotic should be administered in addition to the aminoglycoside, and its mechanism of action that causes microbial death should be different from that of the aminoglycoside.
This antibiotic has a black box warning. Elevated blood concentrations of aminoglycosides may cause significant injury to the kidney and the vestibular/auditory nerve. Concurrent use of furosemide or other loop diuretics and use of vancomycin can increase nephrotoxicity. Thus, peak and trough levels of aminoglycosides in neonatal sera must be measured if their use is going to exceed an initial period of prophylaxis (ie, 48 h after birth) to exclude sepsis.
Aminoglycosides demonstrate concentration-dependent killing of bacteria, suggesting a potential benefit related to higher serum concentrations that are achieved with less-frequent dosing (eg, once daily administration).
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