Randall G. Fisher

When to suspect fungal infection in neonates: A clinical comparison of Candida albicans and Candida parapsilosis fungemia with coagulase-negative staphylococcal bacteremia.

Objectives. To determine the epidemiology of candidemia in our neonatal intensive care unit; to compare risk factors, clinical presentation, and outcomes for neonates infected with Candida albicans, Candida parapsilosis,and coagulase-negative staphylococcus (CoNS); and to suggest a rational approach to empiric antifungal therapy of neonates at risk for nosocomial infection. Design. Retrospective chart review of all neonatal intensive care unit patients with systemic candidiasis or CoNS infection between January 1, 1995 and July 31, 1998 at Duke University Medical Center. Results. Fifty-one patients were reviewed. Nine of 19 patients infected with C parapsilosis and 5 of 15 patients infected with C albicans died of fungemia. Seventeen neonates had >2 positive cultures for CoNS obtained within 96 hours and 1 died. There was no statistically significant difference in birth weight, gestational age, or age at diagnosis between patient groups; however, candidemic patients had a sevenfold higher mortality rate. Before diagnosis, candidemic patients had greater exposure to systemic steroids, antibiotics, and catecholamine infusions. Of the 51 patients, 32 received third-generation cephalosporins in the 2 weeks before diagnosis and 19 did not. Twenty-nine of the 32 who were treated with third-generation cephalosporins subsequently developed candidemia, while candidemia occurred in only 5 of 19 patients who were not treated with cephalosporins. At the time of diagnosis, candidemic patients were more likely to have required mechanical ventilation and were less likely to be tolerating enteral feeding. Multivariate clustered logistic regression analysis revealed that candidemic patients had more exposure to third-generation cephalosporins. Once the clinician was notified of a positive blood culture for Candida, patients infected with C parapsilosis retained their central catheters longer than patients infected with C albicans. Conclusions. In this retrospective review, we were able to identify aspects of the clinical presentation and medication history that may be helpful in differentiating between candidemia and CoNS bacteremia. Those key features may be used by clinicians to initiate empiric amphotericin B therapy in premature neonates at risk for nosocomial infections. Prolonged use of third-generation cephalosporins was strongly associated with candidemia. There was no statistically significant difference in the morbidity and mortality between patients infected with C parapsilosis and those infected withC albicans. Observed delays in removal of the central venous catheter may have contributed to finding a mortality rate fromC parapsilosis that was higher than was previously reported.

Local anesthetic and stylet styles: factors associated with resident lumbar puncture success.

OBJECTIVE. To assess the effects of procedural techniques, local anesthetic use, and postgraduate training level on lumbar puncture (LP) success rates. METHODS. In this prospective observational study, medical students and residents (“trainees”) reported techniques used for infant LPs in an urban teaching emergency department. Data on postgraduate year, patient position, draping, total and trainee numbers of attempts, local anesthetic use, and timing of stylet removal were collected. Logistic regression analysis was used to identify predictors of successful LP, with success defined as the trainee obtaining cerebrospinal fluid with <1000 red blood cells per mm3. RESULTS. We collected data on 428 (72%) of 594 infant LPs performed during the study period. Of 377 performed by trainees, 279 (74%) were successful. Local anesthesia was used for 280 (74%), and 225 (60%) were performed with early stylet removal. Controlling for the total number of attempts, LPs were 3 times more likely to be successful among infants >12 weeks of age than among younger infants (odds ratio [OR]: 3.1; 95% confidence interval [CI]: 1.2–8.5). Controlling for attempts and age, LPs performed with local anesthetic were twice as likely to be successful (OR: 2.2; 95% CI: 1.04–4.6). For infants ≤12 weeks of age, early stylet removal improved success rates (OR: 2.4; 95% CI: 1.1–5.2). Position, drape use, and year of training were not significant predictors of success. CONCLUSIONS. Patient age, use of local anesthetic, and trainee stylet techniques were associated with LP success rates. This offers an additional rationale for pain control. Predictors identified in this study should be considered in the training of physicians, to maximize their success with this important procedure.

Candidal Mycetoma in the Neonatal Kidney

Objective. To determine the natural history of renal mycetoma (fungal balls) in the neonate. Design. Retrospective chart review of all neonatal intensive care unit patients with systemic candidiasis and sonographic evidence of renal mycetoma admitted to the Duke University Medical Center between January 1, 1993, and July 1, 1998. Results. Fourteen patients were reviewed. Three died from fungemia, and 3 died from other causes months after completing treatment. Ten patients had urine cultures obtained within 1 week of diagnosis; each had a positive routine or fungal urine culture for candida. The rate of improvement of renal mycetoma by ultrasound was variable, ranging from 10 days to 4 months and was not predictive of survival or long-term renal function. All patients who were discharged from the hospital had creatinine ≤0.5 mg/dL on discharge. Only 1 patient had surgical intervention (nephrostomy tube placement). Of the 11 patients who survived fungemia, 7 were treated for 3 weeks from the time negative cultures were obtained, while 4 were treated for 5 weeks or more after negative cultures. A declining platelet count was suggestive of fungemia in the patients we reviewed. Conclusions. For our patients with renal mycetoma without complete obstruction (patients continued to have urine output) surgical intervention was rarely necessary, the rate of sonographic improvement neither correlated with clinical course nor necessitated longer therapy, and long-term creatinine levels were normal. Sustained declines in platelet count of 10% per day or more in a neonate on broad-spectrum antibiotics for suspected sepsis may be indicative of fungemia.

Very low prevalence of endophthalmitis in very low birthweight infants who survive candidemia.

OBJECTIVE:Candida species often cause sepsis in very low birthweight (VLBW) infants, leading to formal ophthalmologic evaluation for endophthalmitis. Our experience suggests that endophthalmitis is rare in this setting, and retinal vascular compromise in extreme prematurity may decrease the risk. We studied the prevalence of endophthalmitis in surviving VLBW infants with candidemia.STUDY DESIGN:Epidemiologic data and presence of ROP and endophthalmitis were ascertained for all VLBW infants with candidemia at our institution from 1994 to 2001.RESULTS:A total of 123 infants were included. Median EGA was 25 weeks (range, 23 to 32) and median birthweight was 735 g (range, 426 to 1460). Of these 123, only one had transient retinal findings (prevalence 0.8%; 95% confidence interval 0 to 4%), which resolved during therapy. In no case was either the duration of therapy or the outcome of candidemia altered by retinal examination.CONCLUSIONS:Aggressive treatment of candidemia has made endogenous endophthalmitis rare in candidemic VLBW infants.

Successful Prophylaxis Against Pneumocystis carinii Pneumonia in HIV-Infected Children Using Smaller Than Recommended Dosages of Trimethoprim-Sulfamethoxazole

Prophylaxis against Pneumocystis carinii pneumonia (PCP) is an essential part of the management of children with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS). No dose-ranging studies were ever performed; therefore, the amount of trimethoprim-sulfamethoxazole (TMP-SMX) needed to suppress PCP in children with HIV/AIDS is not known. The dose recommended by the Centers for Disease Control (CDC) has been thought to be just above the threshold needed for prevention, based on anecdotal breakthrough PCP in cancer patients who were improperly dosed. We have been giving prophylaxis based on body weight rather than surface area, and this, combined with growth of our children, has led to a large experience with dosages lower than the currently recommended 150 mg/m2. The medical records of children with HIV who met CDC guidelines for institution of PCP prophylaxis were reviewed. To ascertain the per square meter (m2) dosage each child was receiving, body surface area was calculated from height and weight measurements. Dosages were recalculated every 6 months and at each dosage change. Data regarding PCP infection, bacterial infections, and side effects of TMP-SMX were extracted. Data were compiled from 1,719.5 child-months of TMP-SMX prophylaxis, including 1,532.5 child-months below the currently recommended dose. Sixty-seven percent of our child-months were at or below two-thirds the CDC recommended dose. There were no cases of proven or suspected PCP. Incidence of other serious bacterial infections was low. Bacteremia and sepsis with Streptococcus pneumoniae was the most common proven bacterial infection, at a rate of 5.5 episodes per 100 child-years. The incidence of bacterial infection did not vary by the dose of TMP-SMX. TMP-SMX prophylaxis was well tolerated; most reactions were mild and self-limited and did not recur with re-institution of the drug. Only 6.1% of this cohort had TMP-SMX prophylaxis discontinued due to perceived toxicity. These data show that the currently recommended dose of TMP-SMX (150 mg/m2) may not be required to prevent PCP in children with HIV/AIDS. The drug is well tolerated at all dosage levels. The incidence of serious bacterial infection in this cohort of patients did not depend upon the amount of TMP-SMX prescribed. A prospective, controlled clinical trial of low-dose TMP-SMX for children with HIV infection is warranted.

Exploring the Differential Diagnosis of Hemorrhagic Vesicopustules in a Newborn

Hemorrhagic vesicles in a newborn present a challenging differential diagnosis including both infectious and neoplastic disorders. Patients should be evaluated in an efficient manner to arrive at the correct diagnosis as quickly as possible. We present here an interesting case that outlines the methodical workup that ultimately revealed the diagnosis of congenital Langerhans cell histiocytosis. After a diagnosis of Langerhans cell histiocytosis is made, it is important to evaluate the patient thoroughly for systemic involvement. Historically, the diagnosis of congenital self-healing Langerhans cell histiocytosis was used to delineate a benign self-limited disorder limited to the skin with spontaneous resolution during the first several months of life; this disorder may also be referred to as “self-regressive Langerhans cell histiocytosis.” However, some newborns with initial skin-only Langerhans cell histiocytosis progress to have multisystem disease after spontaneous resolution has occurred. For this reason, the nomenclature is changing. We suggest using the term “skin-only Langerhans cell histiocytosis.” Periodic long-term follow-up is recommended to monitor for relapse or progression to systemic disease.

Virologic and CD4 Response to Treatment with Nelfinavir in Therapy Experienced, Protease Inhibitor Naive HIV-Infected Children: 48 Week Follow-Up

Virologic and CD4 Response to Treatment with Nelfinavir in Therapy Experienced, Protease Inhibitor Naive HIV-Infected Children: 48 Week Follow-Up

Factors Associated With Lumbar Puncture Success: In Reply

In Reply .— We thank Drs Molina and Fons for their interest in our article on resident success of lumbar puncture (LP) and for sharing their data regarding the width of the intravertebral space of infants in the sitting versus the supine position. Their ultrasound results may influence the common debate of sitting versus recumbent position. Position did not remain in our model for efficacy …