December 2004

My guest columnist for this month is again Josué Molina, MD, a pediatrician from Del Rio, Texas. Dr. Molina is a graduate of the medical school in Monterey, Mexico. Dr. Molina began his pediatric training in Mexico City and then came to Scott & White to complete his pediatric residency in 1997. He has been in practice in Del Rio since then, at the United Medical Center, a nonprofit organization that operates using government grants to see the uninsured and underinsured. Dr. Molina also sees pediatric patients at Laughlin Air Force Base.

Case

A 14-month-old girl is admitted from the emergency department of the local hospital for evaluation of lethargy. The problem started about two weeks earlier with the onset of fever up to 104°F and a runny nose. Mother denied any other symptoms at that time, and the patient was treated symptomatically without antibiotics. In the ensuing two weeks, her oral intake and activity level decreased as she continued to spike occasional fevers. A few days prior to admission, the patient was seen again by her primary care provider with ongoing fevers and the development of nausea without emesis or diarrhea. He performed a “sepsis workup” but held antibiotics because the initial studies returned normal. Cerebrospinal fluid (CSF) was not obtained as a part of the sepsis workup. He prescribed Phenergan (promethazine, Wyeth) for the nausea. The day prior to admission, the patient’s mental status and activity level had significantly changed for the worse, but her fever had become less noticeable. She had taken two doses of Phenergan, and her mother denied any possibility of any toxic ingestion.

Her past medical history is positive for being diagnosed with vesicoureteral reflux after a urinary tract infection, and she is being treated with trimethoprim-sulfamethoxazole prophylaxis. She was also jaundiced at birth, requiring phototherapy, and her developmental history is normal for her age. Her review of systems and the rest of her history are otherwise unremarkable. Her family history is positive for cigarette smoking but no sick contacts. There is no known animal exposure. Her immunizations are up to date and documented, and she has no known allergies.

On examination, the child is lethargic but awakens and reacts to stimuli, then falls asleep again. Her vital signs reveal a temperature of 98°F, pulse of 122, respiratory rate of 30 with 99% oxygen saturation on room air and a blood pressure of 101/55 with a capillary refill of two to three seconds. In addition to the lethargy, she is found to have ptosis of her right upper lid and generally decreased muscle tone. The rest of her examination is unremarkable. A complete blood count reveals a white blood cell count of 12,400, with a normal differential, but a platelet count of 1,132,000. A computed tomography (CT) scan of her head is shown in Figures 1-3. The patient is given a bolus of saline (20 cc/kg) and a dose of ceftriaxone and is transferred to a tertiary center where she has surgery, more antibiotics and intensive care.

What’s Your Treatment?

1. Ceftriaxone + vancomycin
2. Cefuroxime + metronidazole
3. Ceftriaxone + clindamycin + vancomycin
4. Ceftriaxone + metronidazole + vancomycin

Answer

Of the choices listed, D is most recommended (a third-generation cephalosporin, metronidazole and vancomycin). The reason for this choice will be explained below.

The patient had a massive subdural empyema that required surgical drainage. The most likely organisms that would cause this infection depend on the underlying pathophysiology or disease process. A wide variety of bacteria have been recovered from these infections, especially when good anaerobic techniques are used.

Itzhak Brook, MD, MSc, professor of pediatrics and medicine at Georgetown University in Washington, has been the leader in the area of anaerobic organisms and the role they play in many different infectious conditions. Dr. Brook’s excellent treatment of this subject in his textbook, “Pediatric Anaerobic Infections, Diagnosis and Management,” chapter 16, “Infections of the Central Nervous System,” is a concise but thorough review. Largely through his work, it is now well recognized that anaerobic bacteria play a significant role in many of these pyogenic infections in and about the brain.

Because of this, it is recommended that metronidazole be part of the initial therapy. It has good central nervous system (CNS) penetration and is effective against the vast majority of anaerobes of the head and neck area. While clindamycin is an excellent anti-anaerobic antimicrobial, it is not recommended for use in CNS infections because of its limited penetration.

As Brook and others have shown, Staphylococcus aureus must also be considered and empirically treated pending culture results, and with the high incidence of methicillin-resistant S. aureus (MRSA), vancomycin is recommended. This also helps cover the possibility of a penicillin- and cephalosporin-resistant Streptococcus pneumoniae. One needs to remember that the starting dose of vancomycin for CNS infections is 60 mg/kg/day, divided every 6 hours. A third-generation cephalosporin, with its excellent CNS penetration, is used to cover most of the aerobes. No combination is going to cover every possibility, but for most cases, this is reasonable. In some situations, fungal, acid-fast organisms or protozoa (toxoplasma) may be likely, calling for a different choice of empiric treatment. These organisms are much less likely in the normal host.

I am certainly no expert on these parameningeal infections. Like most of you, I rely on the published data and experience of those who are. I have already mentioned Itzhak Brook as one of those experts. I should also reference chapter 39 of the new Feigin and Cherry textbook on pediatric infectious diseases. Howard P. Goodkin, MD, PhD, and Scott L. Pomeroy, MD, PhD, put together a very nice and well-organized chapter on this subject. They point out that the empiric treatment can be modified depending on the underlying cause (if known). These causes include direct extension from another site, such as teeth, middle ear, shunts, sinuses, osteomyelitis of the skull as in Pott’s puffy tumor, etc. Other possible causes are mucocutaneous defects, such as a derma sinus (Figure 4) or a nasal glioma as seen in Figure 5 after removal in a patient with recurrent meningitis. Figure 6 shows the repaired area near the cribriform plate where the glioma was located.

The cause is oftentimes unknown, as was the case in the patient presented above. No organism was grown in this case, probably because of the antibiotics received prior to surgical drainage and/or because of inadequate anaerobic culture technique, a frequent cause of “sterile” cultures. It is also noteworthy that the child had a history of complicated urinary tract infections and was on sulfa prophylaxis at the time this occurred. However, whether or not it played a role could not be determined.

Clinically, the symptoms can be rather acute in nature. But oftentimes subdural empyema cases present with symptoms occurring over days to weeks and are usually accompanied by fever, although fever may not be a noteworthy feature, as in this patient. The presenting symptoms obviously depend on a variety of factors, such as the area of the brain most involved, the age of the patient, whether the anterior fontanelle is open or not, under-lying illness or injury, etc. Lab tests may be abnormal but may be of little help, as in this case. While the platelet count was very high, the rest of the CBC was normal. If CSF analysis were done, it would probably appear similar to a case of aseptic meningitis. Also, it should be pointed out that even though one may see radiologic reports and others describing this finding as a subdural abscess, there is a difference between an empyema and an abscess.

According to Dorland’s medical dictionary, an abscess is a collection of pus in a cavity formed by the disintegration of tissue. This results in a wall comprisingnecrotic debris, thickened exudate and congested vessels that will enhance with contrast on CT or MRI imaging, revealing ring enhancement, as seen in Figure 7. An empyema is simply a collection of pus in a cavity or anatomic space of the body. As pointed out by Goodkin and Pomeroy, pus may accumulate over a wide area of the brain because of the anatomy of the subdural space. While the question in this case was in reference to the empiric antimicrobial therapy, I cannot overemphasize the importance of surgical decompression and drainage for therapeutic reasons and microbiological diagnosis.

Postscript and acknowledgements

In response to the October column on nummular eczema with secondary infection, Itzhak Brook correctly pointed out that there are often anaerobic organisms complicating these skin lesions. He published a very nice and concise collection of such cases with 150 secondarily infected skin lesions, revealing a wide array of aerobic and anaerobic microorganisms. You can find this report in the Journal of Medical Microbiology (2002;51:808-812). Of course, if you have Brook’s revised and expanded third edition of his textbook mentioned above, you already have all this information there as well.

I would like to again thank Dr. Molina for contributing these last two cases. I am happy to consider any good case for this column, so if you would like to be a guest columnist, please write me at jhbrien@aol.com. Figures 4, 5 and 6 above are from the Jim Bass collection.

Lastly, I would like to wish you all a most happy and safe holiday season. This is a particularly difficult time of the year for military personnel who are unable to be with their families. So, whether you celebrate Christmas, the Jewish holidays or the month of Ramadan, please keep these brave young people in mind as we celebrate our holiday seasons, especially those deployed in harm’s way. Many of them will never be home for the holidays again. Whether you are happy or unhappy with the outcome of the elections, I believe that this goodwill for our military personnel should always remain above politics.

For more information:

• James H. Brien, DO, Pediatric Infectious Disease, Scott and White’s Children’s Health Center and Associate Professor of Pediatrics, Texas A&M University, College of Medicine, Temple, Texas.
• Josué Molina, MD, general pediatrician practicing in Del Rio, Texas, and Laughlin Air Force Base.