An infant in septic shock _ Commentary
Jones, Clay; Steele, Russell
Clinical Pediatrics
yline: Jones, Clay; Steele, Russell
Volume: 42
Number: 1
ISSN: 00099228
Publication Date:
Page: 85
Type: Periodical
Language: English
Resident Rounds
HEADNOTE
The following Brief Report was written by a resident. A discussion by a member
of the resident's faculty follows. We invite any resident to submit such
articles, together with commentary by a faculty member.
Patient Report
Clay Jones, MD
An 8-month-old white male infant presented to his community hospital with a
1-day history of progressive respiratory distress, decreased feeding, decreased
urine output, and an overall toxic appearance, for which he was transferred to
our children's hospital. His medical history was negative for any prior
illness. He was the product of a full-term delivery by cesarean section with no
perinatal complications and had been regularly breastfed with occasional
formula feeds up to the day of presentation. His immunizations were up to date,
and the only historical finding of note was the recent episode of methicillin-resistant
Staphylococcus aureus (MRSA) cellulitis in the father 2-3 weeks before our
patient's admission.
On physical examination the infant was toxic appearing with suprasternal,
intercostal, and subcostal retractions and stridor. Several erythematous
macules were found on the left upper chest and his extremities were cold and
mottied with delayed capillary refill of 3-4 seconds. Vital signs were as
follows: temperature 101 deg F, heart rate 180 beats/minute, respiratory rate
40 breaths/minute, blood pressure of 77/38 mmHg, and oxygen saturation 80% on
room air. Initial laboratory findings revealed a white blood cell count of
2,200 cells/mm^sup 3^ with a differential of 38% granulocytes, 13% immature
granulocytes, 42% lymphocytes, and 7% monocytes.
Bolus IV fluids were administered and the infant was placed on 30% oxygen in a
hood, and treatment was initiated with vancomycin, cefotaxime, and activated
protein C. Within 24 hours of admission his condition worsened; he developed
acute renal failure requiring peritoneal dialysis and disseminated
intravascular coagulopathy, necessitating several transfusions of fresh frozen
plasma, platelets, and packed red blood cells. The cold and mottled extremities
began to show signs of vascular insufficiency, resulting in necrosis and
subsequently requiring amputation of the arms below the elbow and the legs
below the knees.
Following amputation 3 weeks into his hospital course the
patient's condition improved, repeat cultures were negative, and he remained
afebrile. Throughout his illness his caloric needs were maintained, initially
with total parenteral nutrition (TPN) and subsequently with enteral nasojejunal
tube feeds until he was able to resume bottle and spoonfeeding. The now
10-month-old infant was discharged after 7 weeks of hospitalization.
Blood and urine cultures obtained while at the referral facility were positive
for methicillin-resistant Staphylococcus aureus.
Commentary
Russell Steele, MD
Department of Pediatrics, Children's Hospital, New Orleans, LA
Staphylococcus aureus, a ubiquitous and resilient gram-positive organism, has
been a known cause of bacterial infection since 1882.1 It is responsible for
many nosocomial and community-acquired infections and for toxin-mediated
diseases.2 Though many of these infections occur in patients with predisposing
factors such as congenital and acquired immunodeficient states or the presence
of central venous catheters, it is an increasingly recognized cause of
community-acquired infection in otherwise normal hosts.1
S. aureus remains viable in acidic and high sodium environments and thrives in
wide temperature variations. Infection is most commonly spread by contact with
an infected or colonized individual, usually a patient with an open skin lesion
or respiratory infections but frequently an asymptomatic carrier. In
particular, the anterior nasal vestibule is a common site of chronic
colonization. This potential pathogen may be spread by airborne particles or
contact with a contaminated object, where it may live for several days to a
week.2
The first line of defense against S. aureus infection is intact skin and mucous
membranes. Disorders that disrupt skin and mucous membrane integrity such as
acute burns or chronic eczema increase risk of infection. Patients with
indwelling devices such as cardiac pacemakers, as well as patients with
neutropenia or qualitative neutrophil defects are at greater risk than the
general population.2
The major clinical syndromes of S. aureus infection are subcutaneous abscesses,
osteomyelitis, septic arthritis, scalded skin syndrome, toxic shock syndrome,
sepsis and septic shock, and pneumonia with pleural effusion. A report from the
Centers for Disease Control and Prevention's National Nosocomial Infections
Surveillance system cited S. aureus as the most common cause of
hospital-acquired infection in
Currently, most strains of S. aureus are resistant to penicillin and
ampicillin. These isolates usually remain susceptible to other betalactams that
are penicillinase-resistant such as nafcillin and oxacillin,
penicillin-beta-lactamase inhibitor combinations, and most cephalosporins. In
US hospitals, the percentage of S. aureus isolates resistant to methicillin
(MRSA), and associated with nosocomial infections, has consistently increased
since the 1970s.1 In 1999 the CDC reported that more than 50% of S. aureus
nosocomial infections were methicillin resistant.3 This trend of increasing
resistance to antibiotics has begun to include a greater number of
community-acquired infections (CA-MRSA).
Increasing prevalence of CAMRSA in patients of all ages has challenged the
notion of MRSA confined to hospital environments and associated with risk
factors. At the University of Chicago Children's Hospital, CA-MRSA increased
from 10/100,000 in 1988-1990 to 208/100,000 in 1998-1999, with half of these
isolates found in patients not associated with any predisposing risk factor.4
This trend is not confined to Chicago but has been documented in reports from
Texas, Minnesota, North Dakota, and Hawaii as well as international centers in
Canada and Australia.
Thus far, CA-MRSA isolates have been sensitive to a broad range of antibiotic
agents. Those from patients without risk factors have been more susceptible to
clindamycin and trimethoprimsulfamethoxazole, which can therefore be used for
treatment.4 For those patients with hospital acquired MRSA or for those with
CA-MRSA associated with risk factors such as recent hospitalization, prior
surgical procedure, history of endotracheal tube intubation, chronic disorders,
antibiotic therapy within 6
months, indwelling venous or urinary catheter, or household contact with a
person who works in a health care environment, a glycopeptide such as
vancomycin should be used.4 In patients who do not respond initially to
vancomycin, the addition of rifampin is recommended by some experts.1
Most alarming, however, are reports of S. aureus with intermediate levels of
resistance to the glycopeptides, particularly vancomycin, which has long served
as the major treatment for MRSA. Since 1997 however, when
To date, several newly developed agents, including linezolid and
quinupristin-dalfopristin, appear to be effective clinically.3 Linezolid, an
oxazolidinone, is a synthetic antimicrobial active against MRSA with the
additional advantage of an oral formulation. It has shown good efficacy in the
treatment of bacteremia and skin and soft tissue infection.
Quinupristin-dalfopristin, an injectable streptogramin, is effective for MRSA
infections such as bacteremia, nosocomial pneumonia, and skin and soft tissue
infections.1 Both of these antibiotics exert their antibacterial effect at the
ribosomal level.2 These antimicrobial agents will surely have a prominent role
in the future treatment of resistant strains, but for now their use should be
restricted to staphylococcal infections that do not respond to vancomycin, and
perhaps in the case of linezolid, also be considered for multiresistant MRSA
that can be treated orally. Several experimental drugs, such as the carbapenem
LY 333328, and a new semisynthetic tetracycline are also being developed for
the treatment of multiresistant staphylococci.
Clinical disease associated with community-acquired MRSA as compared to
methicillin-sensitive isolates does not typically differ. Both commonly cause
cellulitis, abscess formation, and superficial skin infections but rarely
produce a bacteremia. Nosocomial infections commonly lead to bacteremia and
central nervous system illness but are similar in clinical outcome regardless
of the antibiotic susceptibility of the S. aureus strain.4 The infant described
in the present case had a much more severe presentation of CA-MRSA than would
be expected with his apparent lack of predisposing risk factors.
With our patient's history of exposure to a close family member with a
documented MRSA infection, there is a high probability of colonization
throughout the household. Most cases of S. aureus bacteremia occur in colonized
patients with most initially colonized in the nasal mucosa.5
The systemic manifestations of this patient's infection and severe sequelae
were suggestive of a toxin-mediated process. Fever, tachycardia, and
hypotension are present in both toxic shock and septic shock; unique to toxic
shock are diffuse erythroderma, delayed desquamation of palms and soles,
conjunctival and pharyngeal hyperemia, muscle injury with high levels of
creatinine phosphokinase, rapidly accelerating renal failure, and
gastrointestinal symptoms.6
Septic shock due to S. aureus infection manifests itself much like that of
infection with gramnegative bacteria. Contact with intact bacteria, peptidoglycan,
or lipoteichoic acid leads to activation of monocytes and macrophages, and
release of tumor necrosis factor alpha and interleukin-1, interleukin-6, and
interleukin-8. Phagocytosis of bacteria by endothelial cells also leads to
release of cytokines. These events result in activation of the complement and
coagulation pathways and increased levels of platelet activating factor. This
leads to fever, hypotension, capillary leak, disseminated intravascular
coagulopathy, depressed myocardial function, and multiorgan pathology.7
By fulfilling some of the criteria for both toxic and septic shock, but not
enough to diagnose either with certainty, it remains unclear which process was
occurring. The existence of a virulence factor, such as toxin production, unique
to this particular strain of S. aureus, is a possibility. Further laboratory
testing on the isolate is underway, and it is hoped this will better elucidate
the pathogenesis.
With trends evident in the recent literature further emphasized by this case,
it would be wise to consider S. aureus as a possible cause of septic shock and
to tailor empiric antibiotic coverage accordingly.
REFERENCES
REFERENCE
1. Paradisi F, Giampaolo C, Messeri D. Antistaphylococcal antibiotics. Med Clin
North Am. 2001;85:16-32.
2. Daum RS, Seal JB. Evolving antimicrobial chemotherapy for Staphylococcus
aureus infections: our backs to the wall. Crit Care Med. 2001;29:481-491.
3. Fridkin SK Vancomycin-intermediate and resistant Staphylococcus aureus: what
the infectious disease specialist needs to know. Clin Infect Dis.
2001;32:108-115.
REFERENCE
4. Hussain FM, Boyle-Vavra S, Bethel CD, et al. Current trends in
community-acquired methicillin-resistant Staphylococcus aureus at a tertiary
care pediatric facility. Pediatr Infect Dis J. 2000;19:1163-1166.
5. Von Eiff C, Becker K, Machka K, et al. Nasal carriage as a source of
Staphylococcus aureus bacteremia. NEnglJMed. 2001;344:11-16.
REFERENCE
6. Todd JK, Fishant M, Keprol F, et al. Toxic-shock syndrome associated with phage-group-1 staphylococci. Lancet. 1978;2:1116-1118.
7. Lowy FD. Staphylococcus aureus infections. NEnglJMed. 1998;339:520-532.
AUTHOR_AFFILIATION
