Perinatal/Neonatal Case Presentation. Necrotizing Staphylococcal Pneumonia in a Neonate ... INTRODUCTION. Staphylococcus aureus pneumonia has been ...
Perinatal/Neonatal Case Presentation Necrotizing Staphylococcal Pneumonia in a Neonate Ryan M. McAdams, MD Edward Mazuchowski, MD Michael W. Ellis, MD Michael Rajnik, MD
Hospitalized neonates are commonly colonized soon after birth with Staphylococcus aureus. The majority of neonates do not develop infectious sequelae; however, premature neonates appear to be more susceptible to serious infections, such as pneumonia. We report a case of an extremely low birth weight infant who developed necrotizing pneumonia due to methicillin-resistant Staphylococcal aureus (MRSA). The MRSA isolate from this neonate is identical to the strains that have been causing primarily community-associated skin and soft tissue infections. The severe course of this patient may be attributed to the presence of the PantonValentine leukocidin gene, a well-known virulence factor leading to soft tissue and pulmonary infections. Journal of Perinatology (2005) 25, 677–679. doi:10.1038/sj.jp.7211364
INTRODUCTION Staphylococcus aureus pneumonia has been reported in infancy and early childhood. Although the current incidence of Staphylococcal pneumonia is low, methicillin-resistant Staphylococcal aureus (MRSA) is emerging as a pathogen-causing pneumonia in both community and hospital settings.1–3 We report a case of an extremely low birth weight infant who developed necrotizing pneumonia due to MRSA that harbored the PantonValentine leukocidin (PVL) gene, a virulence factor that causes soft tissue and pulmonary infections, normally associated with community-acquired MRSA strains.
Department of Pediatrics (R.M.M, M.R.), Brooke Army Medical Center, Wilford Hall Medical Center, San Antonio, TX, USA; Department of Pathology (E.M), Brooke Army Medical Center, Wilford Hall Medical Center, San Antonio, TX, USA; Department of Infectious Disease (M.W.E.), Brooke Army Medical Center, Wilford Hall Medical Center, San Antonio, TX, USA. The opinions expressed in this paper are solely those of the authors and do not represent the views of the United States Air Force, Department of Defense, or the United States Government. Address correspondence and reprint requests to Ryan M. McAdams, MD, Department of Pediatrics, Wilford Hall Medical Center, 2200 Bergquist Dr Suite 1, Lackland AFB, TX 78236, USA.
CASE REPORT Clinical Course This 700 g male infant was born at 25 weeks’ gestation. At 19 days of age, he was noted to be lethargic, pale appearing, and hypoxic. His exam was significant for a distended abdomen and an abdominal radiograph showed free air. Blood, urine, and cerebrospinal fluid cultures were obtained. A complete blood count revealed neutropenia and an absolute neutrophil count of 47/mm3. The patient was intubated and mechanically ventilated. The patient developed signs of shock and DIC. A chest radiograph revealed a large right-sided pneumothorax that was managed with two chest tubes. Initial antimicrobial therapy included intravenous vancomycin, amikacin, and amphotericin. Other management included high-dose pressors, nitric oxide, fluid resuscitation, blood and platelet transfusions, steroids, intravenous immunoglobulin, and granulocyte stimulating factor. Blood cultures grew MRSA. Cerebrospinal fluid and urine cultures were sterile. Subsequent blood cultures repeatedly grew MRSA. The patient continued to deteriorate and died 8 days after onset of symptoms. Pathology and Molecular Biology Autopsy revealed green–black discoloration of the pleura and cut surfaces of the lung. The lungs showed liquefying necrosis and several lobes also had prominent cystic degeneration. Microscopic sections of the lungs demonstrated extensive necrotizing pneumonia with abscess formation, coagulative necrosis, destruction of lung parenchyma, and red blood cell extravasation with multiple foci of Gram-positive bacteria colonies seen in all sections examined (Figures 1 and 2). Post-mortem cultures from the lung tissue had heavy growth of MRSA. Histological sections of the large and small bowel demonstrated normal mucosa and submucosa with no evidence of necrotizing enterocolitis. The MRSA isolate was determined by oxacillin-screening agar and tested for antibiotic susceptibilities by disk diffusion.4 The MRSA isolate was resisitant to ampicillin/sulbactam, cefazolin, oxacillin, and erythromycin. It was susceptible to vancomycin, clindamycin, tetracycline, and trimethoprim-sulfamethoxazole. The clindamycin susceptibilities were confirmed by utilizing a double disk diffusion (D-test) to rule out inducible resistance to clindamycin. Using pulsed-field gel electrophoresis our isolate was determined to be a USA 300 MRSA isolate consistent with community-acquired isolates.5 Additionally, mecA and PVL were detected in a previously described manner.3,6,7 Epidemiology Active surveillance of our NICU found two asymptomatic children colonized with the same strain of MRSA. In retrospective analysis,
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Figure 1. Photomicrograph of lung tissue demonstrating foci of necrotizing pneumonia with abscess formation (hematoxylin and eosin stain; 200 magnification; bar represents 100 mm).
Figure 2. Photomicrograph of lung tissue demonstrating clusters of gram-positive cocci within abscess formation (Brown and Hopps modified Gram stain, 1000 magnification, bar represents 10 mm).
the mother of one of these colonized infants was noted to have an abscess on her leg that required medical attention, but no cultures were obtained. An additional patient developed suppurative submandibular sialadenitis due to an identical strain of MRSA.8
DISCUSSION In the past, studies have shown that S. aureus colonization varies from 20 to 90% over the first week of life.9 A more recent study 678
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found that S. aureus NICU colonization rates were 6.4–13.5 cases per 1000 patient days.10 The skin, nasopharynx, gastrointestinal tract, and umbilical region are common sites of S. aureus colonization in newborns. Most colonizing isolates of the newborn are initially derived from either the nursery staff or immediate environment,11 although newborns with heavy MRSA colonization may serve as the primary reservoir for an outbreak in an intensive care unit setting. Although S. aureus colonization is relatively common in newborns, the development of an infection is uncommon. In a study by Gooch and Britt.12 involving 9423 newborns, 24% were colonized with S. aureus at the time of discharge, however, only 2.3% developed S. aureus infection. The development of infection with S. aureus appears to be related to increased host susceptibility. Premature infants in the intensive care unit are at increased risk for S. aureus infection due to multiple factors: immature immunity, presence of various foreign materials (e.g. central lines, endotracheal, and gastrointestinal tubes), poor nutrition, and prolonged hospitalization. Other factors include disrupted skin integrity due to procedures and tape removal, as well as exposure to broad-spectrum antibiotics that may cause increased selective pressure for the development of resistant organisms. Based on the presence of PVL, resistance to only beta-lactams and erythromycin, and the PFGE typing, we have determined that our patient was infected with a community-acquired MRSA. Most community-acquired MRSA in our region is susceptible to both clindamycin and trimethoprim-sulfamethoxasole differentiating these isolates from nosocomial-acquired isolates. The PVL locus is carried on a bacteriophage that encodes this bicomponent cytotoxin by two contiguous and cotranscribed genes that are present in only a small percentage of S. aureus isolates.13 PVL, which causes leukocyte destruction and tissue necrosis, has been associated with skin infections and necrotizing pneumonia and is found more commonly in community-acquired MRSA.1–3 As previous cases of severe necrotizing pneumonia have been reported in such isolates, the presence of the PVL gene suggests a possible reason for the aggressive nature of this disease process. An additional case of fatal necrotizing pneumonia due to community acquired MRSA was recently described as part of an outbreak in a Houston neonatal intensive care unit.14 In this outbreak, 38% of NICU patients with bloodstream infection due to communityacquired MRSA died. The other cases were complicated by orbital cellulitis, endocarditis, and chronic osteomyelitis. Thus, premature infants may be at an even greater risk for morbidity and mortality when infected with a more virulent organism containing the PVL bacteriophage. Treatment of necrotizing MRSA pneumonia in premature infants has not been well described. Owing to many host factors, our patient did not respond to intravenous vancomycin despite in vitro susceptibilities. Early recognition, prompt removal of Journal of Perinatology 2005; 25:677–679
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potentially infected central lines, more aggressive antibiotic treatment with vancomycin, and supportive measures may prevent adverse outcomes in neonates with necrotizing MRSA infections.
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