Incidence Of Serious Bacterial Infections Research Articles

Intravenous piperacillin/tazobactam plus fluoroquinolone prophylaxis prior to prostate ultrasound biopsy reduces serious infectious complications and is cost effective

Intravenous piperacillin/tazobactam plus fluoroquinolone prophylaxis prior to prostate ultrasound biopsy reduces serious infectious complications and is cost effective Louis C Remynse III, Patrick J Sweeney, Kevin A Brewton, Jay M LonswayUrology Associates of Battle Creek, PC, Battle Creek, MI, USAAbstract: Infectious complications related to prostate ultrasound and biopsy have increased in the past decade with the emergence of increasing fluoroquinolone bacterial resistance. We investigated the addition of intravenous (iv) piperacillin/tazobactam immediately prior to prostate ultrasound and biopsy with standard fluoroquinolone prophylaxis to determine if it would decrease the incidence of serious infectious complications after prostate ultrasound and biopsy. Group 1 patients were a historic control of 197 patients who underwent prostate ultrasound and biopsy with standard fluoroquinolone prophylaxis. Group 2 patients, 104 patients, received standard fluoroquinolone prophylaxis and the addition of a single dose of iv piperacillin/tazobactam 30 minutes prior to prostate ultrasound and biopsy. There were ten serious bacterial infectious complications in group 1 patients. No patients in group 2 developed serious bacterial infections after prostate ultrasound and biopsy. There was approximately a 5% incidence of serious bacterial infection in group 1 patients. Subgroup analysis revealed an almost 2.5 times increased risk of infection in diabetes patients undergoing prostate ultrasound and biopsy. There was a 10% risk of serious bacterial infection in diabetics compared with a 3.8% risk group 1 nondiabetes patients. The addition of a single dose of iv piperacillin/tazobactam along with standard fluoroquinolone prophylaxis substantially reduces the risk of serious bacterial infection after prostate ultrasound and biopsy (P < 0.02).Keywords: piperacillin/tazobactam, fluoroquinolone, prostate biopsy, infectious complications

Intravenous piperacillin/tazobactam plus fluoroquinolone prophylaxis prior to prostate ultrasound biopsy reduces serious infectious complications and is cost effective

Infectious complications related to prostate ultrasound and biopsy have increased in the past decade with the emergence of increasing fluoroquinolone bacterial resistance. We investigated the addition of intravenous (iv) piperacillin/tazobactam immediately prior to prostate ultrasound and biopsy with standard fluoroquinolone prophylaxis to determine if it would decrease the incidence of serious infectious complications after prostate ultrasound and biopsy. Group 1 patients were a historic control of 197 patients who underwent prostate ultrasound and biopsy with standard fluoroquinolone prophylaxis. Group 2 patients, 104 patients, received standard fluoroquinolone prophylaxis and the addition of a single dose of iv piperacillin/tazobactam 30 minutes prior to prostate ultrasound and biopsy. There were ten serious bacterial infectious complications in group 1 patients. No patients in group 2 developed serious bacterial infections after prostate ultrasound and biopsy. There was approximately a 5% incidence of serious bacterial infection in group 1 patients. Subgroup analysis revealed an almost 2.5 times increased risk of infection in diabetes patients undergoing prostate ultrasound and biopsy. There was a 10% risk of serious bacterial infection in diabetics compared with a 3.8% risk group 1 nondiabetes patients. The addition of a single dose of iv piperacillin/tazobactam along with standard fluoroquinolone prophylaxis substantially reduces the risk of serious bacterial infection after prostate ultrasound and biopsy (P < 0.02).

Month-by-Month Age Analysis of the Risk for Serious Bacterial Infections in Febrile Infants With Bronchiolitis

This study's aim was to assess the risk of serious bacterial infections (SBI) in each of the first 3 months in hospitalizes febrile infants with bronchiolitis. The risk of SBI was compared between hospitalized infant with or without bronchiolitis by age in months. A total of 1125 febrile infants aged ≤3 months were admitted during the study period, 948 without and 177 with bronchiolitis. The incidence of SBI was significantly lower among infants with bronchiolitis compared with those without (4% vs 12.2%, P < .001). However, within the subgroup of neonates with bronchiolitis aged ≤28 days, the incidence of SBI was 9.7% and was not significantly lower than in neonates without bronchiolitis. The risk of SBI among febrile infants with bronchiolitis is significantly lower compared with febrile infants without bronchiolitis, but only after the neonatal period in which the risk for urinary tract infection was relatively high (9.7%).

Serious Bacterial Infections in Febrile Outpatient Pediatric Kidney Transplant Recipients

the purpose of this study was to describe the incidence of serious bacterial infections in febrile outpatient pediatric kidney transplant recipients and to assess the utility of using white blood cell indices to identify patients at low risk for bacteremia. a retrospective study was conducted on all kidney transplant recipients followed at a single children's hospital. All outpatient visits from January 1, 1995 to June 6, 2007 in which fever was evaluated were reviewed. Patients with history of a primary immunodeficiency, receiving concurrent chemotherapy, or a stem cell or small bowel transplant were excluded. Demographic, historical, physical examination, laboratory, and radiographic data were then recorded. in all, 101 patients had 251 individual episodes of fever evaluation. In 209 visits, a blood culture was drawn with results available. There were 21 (10.0%) true positive blood cultures and 3 (1.4%) false positives. Two-thirds of the true positive blood cultures occurred in patients with indwelling hardware. There was a positive urine culture in 52/192 (27.1%) visits. Pneumonia was diagnosed in 14/74 (18.9%) visits. In nonill-appearing children without indwelling central lines or focal bacterial infections, the incidence of bacteremia was zero. No practical decision rule based on white blood cell indices could be derived. the majority of bacteremic cases in febrile outpatient pediatric kidney transplant patients occurred in patients with indwelling hardware. We did not detect any occult cases of bacteremia in this study cohort. A larger prospective multicenter study is required to confirm the low incidence of bacteremia in this patient subset.

Oral Antibiotic Prophylaxis of Early Infection In Multiple Myeloma: A URCC/ECOG Phase III Study

AbstractAbstract 3017 Introduction:Multiple myeloma (MM) is a malignancy of clonal plasma cells with resulting in an increase production of ineffective immunoglobulins with suppression of non-involved immunoglobulins. Patients with MM are at increased risk of infectious complications, particularly to those organisms in which opsonization is one of the key defense mechanisms, e.g. strep and staph infections. Treatment of MM is virtually always associated with further immunosuppression, at least in the immediate term, until the malignant clone is eradicated and normal immunoglobulins are produced. Rationale:Due to further compromise of an already incompetent immune system by initial chemotherapy and the previous suggestion (Oken et al Am J Med 1996; 100:624-628) that prophylactic antibiotics may reduce infectious complications, this study was designed to evaluate the impact of prophylactic antibiotics on the incidence of serious bacterial infections during the first two months of treatment. Methods:Pts with untreated MM receiving chemotherapy were randomized on a 1:1:1 basis to receive either a daily ciprofloxacin (C; 500 mg), trimetheprim-sulfamethoxazole (T; DS bid) or observation (O) for the first 2 months of treatment. Pts were evaluated for serious bacterial infection (grade 3 or 4) during the first two months of myelotoxic/suppressive therapy. Secondary endpoints (EP) included: incidence of non-bacterial infections, resistant organisms due to prophylaxis, the incidence of infection the third month OFF of antibiotic prophylaxis and whether protection against infection is associated with an improved response rate. Results:From July 1998 to January 2008, 212 untreated, symptomatic MM pts being treated with myelotoxic/suppressive chemotherapy were randomized to C (n=69), T (n=76) or O (n=67) for the first 2 months of treatment. The incidence of serious infection (> grade 3 ECOG toxicity criteria and/or hospitalization) was comparable among groups: C=10 (14.7%), T=5 (6.9%), O=9 (14.5%); p= 0.268 which was the primary EP. The incidence of any infection during the first 2 months was also comparable (20% vs 23% vs 22%, respectively, p=0.910). There were 25 grade 2 infections and 4 grade 3 infections involving respiratory (n =13), sepsis/bacteremia (n = 4), and urinary (n =3), joint/bone (n =2), unknown (n =2) or various GI tract (n = 5) and skin (n =1). Eight pts expired within the first 2 months: 2 from MM, 3 cardiac, 2 respiratory, 1 renal (unrelated to MM or Rx) occurring in the C (4), T (1), O (2). Secondary EPs failed to show a difference in the incidence of serious bacterial infection during the third month in the absence of prophylaxis (C=3%, T=4%, O=2%; p=0.874), development of resistant infections, initial response to therapy or overall survival. Conclusions:The use of prophylactic antibiotics did not decrease the incidence of serious infection (> grade 3 and/or hospitalization) nor of any infection within the first 2 months of treatment. Infection prophylaxis did not affect the incidence of infection upon completion of 2 months of therapy (nor, ultimately, at any time during the subsequent 2 years), the response to therapy or to overall survival. Incidentally, there were no documented cases of PCP despite the assumption that MM pts, with compromised immune systems, are more susceptible.The incidence of serious infections in this study, in which few patients received novel agents, is comparable to that observed in more modern regimens even in the presence of mandated/recommended prophylactic antibiotics. Utilizing either lenalidomide plus dexamethasone or clarithromycin, lenalidomide and dexamethasone resulted in > grade 3 infectious complications in 16.7% and 9.7%, respectively, as reported by the Mayo Clinic and Cornell groups, respectively (Gay et al Am J Hematol, in press). Furthermore, in the ECOG E4A03 randomized trial of lenalidomide plus either high dose dexamethasone (LD) or low dose dexamethasone (Ld) in which prophylactic antibiotics were recommended, the incidence of > grade 3 infectious complications were 9.4% and 6.4%, respectively (Rajkumar et al Lancet Oncol 2010; 11: 29–37). We conclude that routine use of prophylactic antibiotics should not be mandated for patients receiving induction chemotherapy. Prophylactic antibiotics should be considered on a case-by-case basis after analyzing the potential infection risk in individuals. Disclosures:No relevant conflicts of interest to declare.

Risk of Serious Bacterial Infection in ALTEs

Source: Mittal M, Shofer F, Baren J. Serious bacterial infection in infants who have experienced an apparent life-threatening event. Ann Emerg Med. 2009; 54:(4) 523– 527; doi: 10.1016/j.annemergmed.2008.12.037To determine the incidence of serious bacterial infection (SBI) among infants who experience an apparent life-threatening event (ALTE), investigators at the Children’s Hospital of Philadelphia performed a prospective observational study. Between June 2006 and May 2007, infants younger than 12 months presenting to the emergency department (ED) with a history of ALTE were prospectively enrolled. The National Institutes of Health consensus statement was used to define ALTE,1 characterized by some combination of apnea, color change, choking, gagging, or marked change in muscle tone. Infants with a clear alternative medical diagnosis at the time of presentation (eg, febrile seizure or bronchiolitis) were excluded.A standardized interview of parents or guardians of enrolled infants was conducted and the physical examination performed by the ED physician was recorded. Medical records were reviewed to establish the hospital course and final diagnosis. The primary outcome of SBI was defined as detection of a bacterial pathogen in blood, urine, or cerebrospinal fluid. Parents or guardians of all enrolled infants were surveyed by telephone four weeks after the ED visit to detect missed cases of SBI.During the study period, 228 infants met the study definition for ALTE. Parents or guardians of 12 infants refused consent and 18 infants were missed. The median age of enrolled infants was 49.5 days and 34% were born prematurely. The rate of hospital admission was 76%. While only 4.5% of infants experienced fever during the ED visit, 22% underwent some component of an evaluation for SBI (19% had a blood culture, 18% had a urine culture, and 9% had a cerebrospinal fluid culture). There were no true positive culture results. Of the 154 infants who did not undergo any component of SBI evaluation, none were found to have an SBI during the four-week follow-up interview. Only 1 of the 198 families was unable to be reached for telephone follow-up. This infant was 3 days old with hyperbilirubinemia at the time of ED evaluation and had negative blood and urine cultures. Two other infants with ALTE were diagnosed with enteroviral meningitis (8-week-old premature twins) and did undergo a full evaluation for SBI which was negative. Approximately 9% of infants in the cohort were found to have evidence of a viral infection.The authors report that the incidence of SBI among infants presenting to the ED with a history of ALTE is very low (95% CI, 0%–1.8%). Therefore, the investigators conclude that routine full evaluation for SBI in well-appearing infants is unnecessary.ALTEs occur at an estimated frequency of 2.46 per 1,000 live births2 and are a common cause of ED visits in young infants. The diagnostic evaluation and management of infants presenting with a history of ALTE varies widely.3 (For information about risk factors for extreme events in infants hospitalized for ALTE, see AAP Grand Rounds, June 2009;21:66.4)While participating pediatric emergency medicine physicians ordered testing for SBI less frequently than previously reported,5 the study’s conclusions are strengthened by the excellent rate of follow-up. The authors acknowledge that although no infant in the study was found to have a urinary tract infection (UTI), rates of UTI among infants with ALTE range from 0% to 8% in the existing literature.6–8Even though this study was performed at a single institution, both its large size and prospective methodology provide practitioners with further evidence that most infants with ALTE need not undergo invasive testing for bacterial illness with blood and cerebrospinal fluid cultures. Physicians should continue to evaluate infants experiencing ALTE who appear ill or have other signs of infection for SBI as clinically warranted.

Serious Bacterial Infections in Febrile Outpatient Pediatric Heart Transplant Recipients

The purpose of this study was to describe the incidence of serious bacterial infections (SBIs) in febrile outpatient pediatric heart transplant recipients and to assess the utility of using white blood cell (WBC) indices to identify patients at low risk for bacteremia. A retrospective study was conducted on all heart transplant recipients followed at a single children's hospital. All outpatient visits from January 1, 1995, to June 1, 2007, in which fever was evaluated were reviewed. Patients with history of a primary immunodeficiency, receiving concurrent chemotherapy, or having had a stem cell or small bowel transplant were excluded. Demographic, historical, physical examination, laboratory, and radiographic data were then recorded. Sixty-nine patients had 238 individual episodes of fever evaluation; of these, 217 (91.2%) had blood cultures drawn with results available in their initial evaluation. There were six (2.8%) true-positive blood cultures and eight (3.7%) false-positive cultures. Chest radiography was done in 185 evaluations (77.8%), and 44 episodes of pneumonia (23.8%) were diagnosed. Of 112 urine cultures done, one (0.9%) was positive. Neither of two lumbar punctures performed were positive. In non-ill-appearing children without indwelling central lines or focal bacterial infections (pneumonia, cellulitis), the incidence of bacteremia was 1.2%. In children with a focal bacterial infection, the rate of bacteremia was 6.3%. WBC indices were not significantly different between bacteremic and nonbacteremic patients. A band-to-neutrophil ratio (BNR) of > or =0.25 and a published guideline for identifying low-risk infants using WBC indices identified all bacteremic patients, each with a sensitivity of 100% (95% confidence interval [CI] = 48% to 100% and 54% to 100%, respectively). The incidence of bacteremia was low in febrile, outpatient pediatric heart transplant patients, especially in those who were not ill-appearing and did not have a focus of serious infection. Two different low-risk criteria performed well in identifying the bacteremic patients, although given the low number of true-positive cultures, the CIs for the sensitivities of these tests were extremely wide, and neither test could be reliably used at present. A prospective multicenter study is required to confirm the low incidence of bacteremia and low-risk criteria in this population.

Ancillary testing in children with rotavirus gastroenteritis

Costly microbiological assays are frequently performed in patients with rotavirus gastroenteritis (RGE) to exclude concurrent serious bacterial infection (SBI). The incidence of concurrent SBI in this population is unknown but estimated to be low. The primary objective was to describe the incidence of SBI in children with RGE. The secondary objective was to elucidate risk factors for prolonged length of stay (LOS) in the cohort. All children < or =18 years seen at a community hospital for laboratory-confirmed RGE over a 4-year period were included in a retrospective cohort study to describe the incidence of concurrent SBI and to identify risk factors for prolonged LOS. Prolonged LOS was defined as hospitalization for > or =3 days. Ninety-four cases of RGE were identified; 58 (61.7%) males and 80 (85.1%) African Americans. The median age was 8 months (interquartile range [IQR], 1 month to 16 years) and 83 patients (88.3%) required admission. There were no cases of SBI. The median LOS was 2 days. Age < or = 6 months (adjusted odds ratio [OR], 3.0; 95% confidence interval [CI], 1.2-7.7; P = 0.022) and collection of a peripheral blood culture (adjusted OR, 2.7; 95% CI, 1.0-7.1; P = 0.043) were associated with LOS > or = 3 days. In children evaluated at a community hospital with laboratory-confirmed RGE, no episodes of SBI occurred. This finding challenges the need to perform invasive, costly, microbiological assays to exclude concurrent SBI in this population. Children 6 months and younger were at increased risk of prolonged hospitalization from RGE.

Serious Bacterial Infections in Infants Who Have Experienced an Apparent Life-Threatening Event

We determine the incidence of serious bacterial infection in infants presenting to the emergency department (ED) with an apparent life-threatening event. This was a prospective cohort study of infants younger than 12 months who were treated at an urban children's hospital ED during 1 year and who met standard criteria for an apparent life-threatening event. Sociodemographic data, presenting features, diagnostic testing, hospital course, and final diagnosis were collected. Follow-up information was obtained 4 weeks after the visit. Of the 198 infants enrolled, 44 (22.2%) had evaluation for serious bacterial infection: urine culture 36 (18%), blood culture 38 (19%) and cerebrospinal fluid culture 18 (9%). No infant (0/198; 95% confidence interval 0% to 1.8%) was found to have bacteremia, urinary tract infection, or bacterial meningitis, which was confirmed at the 4-week interview (99% ascertainment). Two infants were found to have enteroviral meningitis. The incidence of serious bacterial infection in this cohort was extremely low. Infants presenting with an apparent life-threatening event need not be subjected to a full serious bacterial infection evaluation routinely.

Anti–tumor necrosis factor α therapy and the risk of serious bacterial infections in elderly patients with rheumatoid arthritis

To assess the association between the initiation of anti-tumor necrosis factor alpha (anti-TNFalpha) therapy and the risk of serious bacterial infections in routine care. This was a cohort study of patients with rheumatoid arthritis (RA) in whom specific disease-modifying antirheumatic drugs (DMARDs) were initiated. Patients were Medicare beneficiaries ages 65 years and older (mean age 76.5 years) who were concurrently enrolled in the Pharmaceutical Assistance Contract for the Elderly provided by the state of Pennsylvania. A total of 15,597 RA patients in whom a DMARD was initiated between January 1, 1995 and December 31, 2003 were identified using linked data on all prescription drug dispensings, physician services, and hospitalizations. Initiation of anti-TNFalpha therapy, cytotoxic agents other than methotrexate (MTX), noncytotoxic agents, and glucocorticoids was compared with initiation of MTX. The main outcome measure was serious bacterial infections that required hospitalization. The incidence of serious bacterial infections was, on average, 2.2 per 100 patient-years in this population (95% confidence interval [95% CI] 2.0-2.4). Glucocorticoid use doubled the rate of serious bacterial infections as compared with MTX use, independent of previous DMARD use (rate ratio [RR] 2.1 [95% CI 1.5-3.1]), with a clear dose-response relationship for dosages >5 mg/day (for < or = 5 mg/day, RR 1.34; for 6-9 mg/day, RR 1.53; for 10-19 mg/day, RR 2.97; and for > or = 20 mg/day, RR 5.48 [P for trend < 0.0001]). Adjusted models showed no increase in the rate of serious infections among initiators of anti-TNFalpha therapy (RR 1.0 [95% CI 0.6-1.7]) or other DMARDs as compared with initiators of MTX. In a large cohort of patients with RA, we found no increase in serious bacterial infections among users of anti-TNFalpha therapy compared with users of MTX. Glucocorticoid use was associated with a dose-dependent increase in such infections.

Duration of fever and markers of serious bacterial infection inyoung febrile children

Despite the drastic change in the evaluation of the febrile young child due to the decreased incidence of serious bacterial infections (SBI) effected by Haemophilus influenza type B and pneumococcal vaccine, there remains a small role for blood work in the evaluation of these patients. Bacterial markers including white blood cell (WBC) count, absolute neutrophil count (ANC) and C-reactive protein (CRP) have been studied and are widely used as predictors of SBI in febrile children. It has been suggested that CRP values should be interpreted cautiously when fever has been present <12 h based on the kinetics of this biological marker. This limitation has not been previously addressed with CRP, nor was it described with other markers, specifically WBC and ANC, therefore the purpose of the present paper was to assess WBC, ANC and CRP values as predictors of SBI in relation to duration of fever. Patients who presented to a pediatric emergency department between the ages of 1 and 36 months, with fever > or =39 degrees C and no source of infection had a complete blood count (CBC) blood culture, and CRP level drawn. A urinalysis and/or urine culture was obtained when age and gender appropriate. A chest X-ray was performed at the discretion of the treating physician. The study subjects were enrolled prospectively and then divided into two groups based on duration of fever of < or = or >12 h, and compared. One hundred and twenty-eight patients were originally enrolled. Nine patients were excluded. Seventeen patients (14%) had SBI. One patient (<1%) had bacteremia, three (3%) had pneumonia, and 13 (10%) had urinary tract infections. Forty-five patients presented with fever < or =12 h and 74 patients presented with fever >12 h. Area under the curve (AUC) for WBC, ANC and CRP was significantly larger in patients with SBI presenting with fever >12 h (0.85, 0.83, 0.92 respectively) compared to patients with SBI who presented with fever for <12 h (0.37, 0.42, 0.68 respectively). Bacterial markers studied were more predictive of SBI if the duration of fever was >12 h as shown by the AUC. CRP performed better than WBC and ANC in both scenarios.

Granulocyte functions and changes in ability with age in newborns; Report no. 2: Activation of granulocyte functions by cytokines

The aim of the present study was to examine the function of granulocytes in newborns from the perspective of granulocyte activation by cytokines. Granulocytes were stimulated with tumor necrosis factor-alpha, granulocyte-macrophage colony stimulating factor (GM-CSF) or granulocyte colony stimulating factor, and the reactivity of granulocytes to these substances was then compared between newborns (umbilical cord blood, peripheral blood obtained at age 5 days and at age 1 month) and peripheral blood obtained from adults. In addition, the expression of cytokine receptors on the surface of granulocytes was measured for each age group. The amplification of CD11b expression on the surface of granulocytes and suppression of l-selectin expression were weaker for cord blood regardless of which cytokine was added. In addition, the increases in the activity of intracellular elastase when stimulated with tumor necrosis factor-alpha or GM-CSF were significantly lower for cord blood. Moreover, the expression of GM-CSF receptors and granulocyte colony stimulating factor receptors on the surface of granulocytes was lower for cord blood, and this expression approached the level found in adults as age increased. Granulocytes during early infancy exhibit low reactivity to inflammatory cytokines, and this was considered to be one of the factors contributing to the higher incidence of serious bacterial infections in infants.

The Rate of Serious Bacterial Infections Among HIV-Infected Children With Immune Reconstitution Who Have Discontinued Opportunistic Infection Prophylaxis

Receipt of highly active antiretroviral therapy is associated with a decrease in the incidence of opportunistic infections (OIs) among HIV-infected adults. The goal of Pediatric AIDS Clinical Trials Group protocol 1008 was to evaluate prospectively the incidence of serious bacterial infections (SBIs) and other OIs after discontinuation of OI and/or Pneumocystis jiroveci pneumonia (PCP) prophylaxis among HIV-infected pediatric subjects who experienced immune reconstitution while receiving stable antiretroviral therapy. HIV-infected children and adolescents, 2 to 21 years of age, who had received OI and/or PCP prophylaxis for > or =6 months were enrolled if they had sustained responses (>16 weeks before study entry) to antiretroviral therapy, with CD4+ cell percentages of > or =20% for patients >6 years of age or > or =25% for patients 2 to 6 years of age. Prophylaxis was discontinued at entry. To identify whether any correlation existed between functional immune reconstitution and protection from OIs, subjects were immunized with the hepatitis A virus vaccine. The association between the humoral immune response and the likelihood of developing an OI was evaluated. A total of 235 HIV-infected subjects from 43 participating sites had a median follow-up period of 132 weeks, yielding 547 person-years of observation. Twenty SBIs were observed among 19 subjects, resulting in an incidence rate of 3.66 SBIs per 100 person-years (95% confidence interval: 2.24-5.66 SBIs per 100 person-years). Sixteen of the events were presumed bacterial pneumonia, with 4 proven SBIs. One participant experienced 2 separate pneumonia episodes, of presumed bacterial cause. Ten subjects who developed SBIs had baseline CD4+ cell counts of > or =750 cells per mm3, and 15 had CD4+ cell percentages of > or =25% at the time of their SBIs. Two subjects died as a result of non-SBI-related causes. There were no statistically significant differences in changes over time in CD4+ cell counts or CD4+ cell percentages between subjects who experienced primary end points and those who did not. There was no evidence that baseline protease inhibitor use, gender, race/ethnicity, age, or CD4+ cell count or percentage affected the time to development of a SBI. OI or PCP prophylaxis can be withdrawn safely for HIV-infected pediatric patients who experience CD4+ cell recovery while receiving stable antiretroviral therapy. More studies are needed to assess the association between antibody responses to neoantigens and the development of SBIs.

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.

Neutropenia and Bacterial Infection in Acquired Immunodeficiency Syndrome

In human immunodeficiency virus (HIV) disease, neutropenia occurs most commonly in patients who are also severely immunosuppressed. It is not currently known whether neutropenia is an independent risk factor for the development of bacterial infection, which is a potentially serious complication of advanced HIV disease. We compared the incidence of bacterial infection between 118 neutropenic patients (absolute neutrophil count [ANC], < 1 x 10(9)/L) and 118 nonneutropenic patients matched for CD4+ lymphocyte count, use of injecting drugs, and follow-up time from a demographically heterogeneous urban cohort of HIV-infected patients followed up longitudinally at the Johns Hopkins Hospital. The incidence of serious infection was analyzed separately for patients with an ANC of less than 1, less than 0.75, or less than 0.5 x 10(9)/L. There were no statistically significant associations found between neutropenia and several individual bacterial infections, including bacteremia, pneumonia, endocarditis, bacterial enterocolitis, and infection of normally sterile sites for any level of neutropenia. However, for all these infections combined, the adjusted relative risk for the occurrence of bacterial infection was 2.33 (95% confidence interval, 1.00 to 5.40; P = .05) for patients with an ANC of less than 1 x 10(9)/L and 7.92 (95% confidence interval, 1.18 to 53.2; P = .03) for those with an ANC of less than 0.5 x 10(9)/L. The incidence of serious bacterial infection ranged from two to three infections per 100 person-months of neutropenia for patients with an ANC of less than 1 x 10(9)/L and three to five infections per 100 person-months of neutropenia for patients with an ANC of less than 0.5 x 10(9)/L for all bacterial infections combined. Our matched cohort analysis indicates that neutropenia is an independent risk factor for bacterial infection in patients with advanced HIV disease. Given the incidence of infection, the cost-effectiveness of interventions to prevent neutropenia in advanced HIV disease should be assessed.

THE ROLE OF THE SPLEEN IN IMMUNITY

IN VIEW Of the success of splenectomy in dealing with certain clinical problems, and the lack of any clearly unfavorable effects of this procedure, the idea that the spleen is not physiologically essential has been widely accepted. The first serious challenge to this concept arose with the clinical observation of King and Schumaker of a high incidence of serious bacterial infection following splenectomy performed in infancy. This original report has been supplemented during the last decade by additional clinical data, and renewed interest in the role of the spleen in immunity has resulted. Recent experimental data have defined more clearly immunological functions for the spleen that are of special significance during early development. The purposes of this are paper are (1) to review the clinical problem which led to re-examination of the role of the spleen in immunity, particularly, as it relates to the early development of the immune mechanism, and (2) to offer a hypothesis which may explain the clinical observation of overwhelming infection after splenectomy in the young infant. THE CLINICAL PROBLEM In 1952 King and Schumaker reported an unusual incidence of infection in infants who had undergone splenectomy for congenital hemolytic anemia. The hazards of splenectomy in early life were pointed out in a number of papers which appeared subsequently with large series of cases reinforcing the validity of the earlier observations. Most recently Horan and Colbatch have incisively reviewed the problem and added a number of their own cases to those already in the literature. In spite of the preponderance of evidence, dissenting reports have appeared and the subject remains somewhat controversial.