Beta-lactam resistance: clinical implications for pediatric patients.

The emergence of resistance to established antibiotic agents such as beta-lactams has been reported worldwide and poses a serious challenge to the management of pediatric infections. The most common mechanism of resistance involves the production of an enzyme that inactivates the antibiotic before it can be effective. Streptococcus pneumoniae, the most common cause of pediatric respiratory tract infections, exhibits variable resistance to penicillins and aminopenicillin due to alterations in its penicillin-binding proteins (PBPs). Haemophilus influenzae and Moraxella catarrhalis show moderate and high beta-lactamase-mediated resistance to aminopenicillins, although they remain susceptible to beta-lactam/beta-lactamase inhibitor combinations. Methicillin-resistant Staphylococcus aureus, a frequent cause of skin and soft-tissue infections, has shown PBP-mediated beta-lactam resistance, prompting the wide-spread use of vancomycin to eradicate this pathogen. Finally, PBP-mediated resistance has been observed in a large proportion of isolates of coagulase-negative staphylococci, which account for a high proportion of nosocomial infections, particularly in neonatal intensive care units. The challenge is to control the emergence of beta-lactamase-mediated resistance by using beta-lactams judiciously. In this regard, the beta-lactam/beta-lactamase inhibitor combinations have an important role to play in extending the usefulness of established beta-lactam agents.

Optimisation of the prevention and treatment of bacterial endocarditis.

This paper reviews currently established guidelines for the prevention and treatment of bacterial endocarditis. Endocarditis remains a life-threatening disease with substantial morbidity and mortality. Primary prevention of endocarditis, whenever possible, is therefore very important. In an individual with endocarditis, rapid diagnosis and effective treatment are essential to good patient outcome. The guidelines discussed here are largely based on those issued by the American Heart Association. While most cases of endocarditis are not attributable to an invasive procedure, certain procedures are associated with bacteraemia by organisms commonly associated with endocarditis, and antibacterial prophylaxis is recommended before such procedures. Patient cardiac conditions are stratified into high, moderate and negligible risk categories based on potential outcome if endocarditis develops. For oral, dental, respiratory tract, and oesophageal procedures (most often associated with viridans streptococci) the standard antibacterial regimen is oral amoxicillin. For gastrointestinal and genitourinary procedures (most often associated with enterococci), parenteral antibacterials are most often recommended. For high-risk patients, intramuscular or intravenous ampicillin and gentamicin (or vancomycin and gentamicin in penicillin-allergic individuals) is recommended. For moderate risk patients, an option of oral amoxicillin or parenteral ampicillin is offered. Treatment of bacterial endocarditis is guided by identification of the causative micro-organism. Approximately 80% of cases of endocarditis are due to the gram-positive cocci: streptococci and staphylococci. Other gram-positive organisms include enterococci (predominantly Enterococcusfaecalis and E. faecium) and the HACEK group of organisms (Haemophilus parainfluenzae, H. aphrophilus, Actinobacillus [Haemophilus] actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae). In general, for uncomplicated cases of endocarditis due to penicillin-susceptible viridans streptococci or Streptococcus bovis 4 weeks of benzylpenicillin (or ceftriaxone) is the preferred regimen for most patients aged >65 years. A 2-week course of treatment can be used when gentamicin is added, in patients at low risk for adverse events caused by gentamicin therapy. When endocarditis is caused by strains of viridans streptococci or S. bovis relatively resistant to penicillin, or by enterococci, both benzylpenicillin and gentamicin are recommended. For staphylococcal endocarditis on native heart valves, nafcillin or oxacillin with or without gentamicin is the preferred regimen. In prosthetic valve staphylococcal endocarditis, nafcillin (or oxacillin) with rifampicin and gentamicin is recommended. For all of the above situations, vancomycin is recommended for the patient allergic to penicillin (or methicillin). Finally, consideration of out-of-hospital therapy in selected patients is discussed.

Moraxella catarrhalis bacteremia: a 10-year experience.

BACKGROUND: Moraxella catarrhalis commonly inhabits the upper respiratory tract and is a cause of acute otitis media and sinusitis in children. It is an infrequent cause of invasive disease. METHODS: We reviewed records of all patients with positive blood cultures for M catarrhalis admitted to our hospital during the 10-year period (1988 through 1997). RESULTS: Eleven cases were identified. Age range was 11 to 32 months. Four (44%) had risk factors for infection, including sickle cell disease (2), acquired immunodeficiency syndrome (AIDS) (1), and leukopenia (1). Upper respiratory symptoms and fever were present in all patients. Ten had acute otitis media, five had sinusitis, and three had pneumonia. All isolates were beta-lactamase producers. Treatment included intravenous cefuroxime (8), cefotaxime (2), and ceftazidime (1), followed by oral amoxicillin/clavulanate or cefuroxime axetil. CONCLUSION: Moraxella catarrhalis bacteremia should be considered in febrile young children with upper respiratory infections and/or acute otitis media especially in those with underlying immune dysfunction.

Are the Duke criteria superior to the Beth Israel criteria for the diagnosis of infective endocarditis in children?

Accurate diagnosis of infective endocarditis may be difficult. The Beth Israel criteria and the newer Duke criteria assign probability to the diagnosis of infective endocarditis on the basis of the presence of common features and manifestations. We reviewed 111 cases of pediatric infective endocarditis diagnosed and treated over 19 years. Each case was classified by the two criteria, and the results were compared. Of 111 cases, 73 (66%) and 18 (16%) were classified as definite by the Duke criteria and the Beth Israel criteria, respectively. No cases were rejected by the Duke criteria, while 21 (19%) of 111 were rejected by the Beth Israel criteria. In 18 pathologically proven cases, reanalysis without pathological data showed that the Duke criteria had significantly greater sensitivity (83%) than the Beth Israel criteria (67%) (P < .03). Echocardiographic evidence was required in 22 cases for definite classification by the Duke criteria; none were rejected, however, when echocardiographic findings were ignored. Our results suggest that the Duke criteria are superior to the Beth Israel criteria for the diagnosis of pediatric infective endocarditis.

Preventing bacterial endocarditis: American Heart Association guidelines.

The American Heart Association recently revised its guidelines for the prevention of bacterial endocarditis. These guidelines are meant to aid physicians, dentists and other health care providers, but they are not intended to define the standard of care or to serve as a substitute for clinical judgment. In the guidelines, cardiac conditions are stratified into high-, moderate- and negligible-risk categories based on the potential outcome if endocarditis develops. Procedures that may cause bacteremia and for which prophylaxis is recommended are clearly specified. In addition, an algorithm has been developed to more clearly define when prophylaxis is recommended in patients with mitral valve prolapse. For oral and dental procedures, the standard prophylactic regimen is a single dose of oral amoxicillin (2 g in adults and 50 mg per kg in children), but a follow-up dose is no longer recommended. Clindamycin and other alternatives are recommended for use in patients who are allergic to penicillin. For gastrointestinal and genitourinary procedures, the prophylactic regimens have been simplified. The new recommendations are meant to more clearly define when prophylaxis is or is not recommended, to improve compliance, to reduce cost and the incidence of gastrointestinal side effects, and to approach more uniform worldwide recommendations.

Prevention of bacterial endocarditis: recommendations by the American Heart Association.

OBJECTIVE: To update recommendations issued by the American Heart Association last published in 1990 for the prevention of bacterial endocarditis in individuals at risk for this disease. PARTICIPANTS: An ad hoc writing group appointed by the American Heart Association for their expertise in endocarditis and treatment with liaison members representing the American Dental Association, the infectious Diseases Society of America, the American Academy of Pediatrics and the American Society for Gastrointestinal Endoscopy. EVIDENCE: The recommendations in this article reflect analyses of relevant literature regarding procedure-related endocarditis, in vitro susceptibility data of pathogens causing endocarditis, results of prophylactic studies in animal models of endocarditis and retrospective analyses of human endocarditis cases in terms of antibiotic prophylaxis usage patterns and apparent prophylaxis failures. MEDLINE database searches from 1936 through 1996 were done using root words endocarditis, bacteremia and antibiotic prophylaxis. Recommendations in this document fall into evidence level III of the U.S. Preventive Services Task Force categories of evidence. CONSENSUS PROCESS: The recommendations were formulated by the writing group after specific therapeutic regimens were discussed. The consensus statement was subsequently reviewed by outside experts not affiliated with the writing group and by the Science Advisory and Coordinating Committee of the American Heart Association. These guidelines are meant to aid practitioners but are not intended as the standard of care or as a substitute for clinical judgment. CONCLUSIONS: Major changes in the updated recommendations include the following: (1) emphasis that most cases of endocarditis are not attributable to an invasive procedure; (2) cardiac conditions are stratified into high-, moderate- and negligible-risk categories based on potential outcome if endocarditis develops; (3) procedures that may cause bacteremia and for which prophylaxis is recommended are more clearly specified; (4) an algorithm was developed to more clearly define when prophylaxis is recommended for patients with mitral valve prolapse; (5) for oral or dental procedures the initial amoxicillin dose is reduced to 2 g, a follow-up antibiotic dose is no longer recommended, erythromycin is no longer recommended for penicillin-allergic individuals, but clindamycin and other alternatives are offered.

Prevention of bacterial endocarditis. Recommendations by the American Heart Association.

OBJECTIVE: To update recommendations issued by the American Heart Association last published in 1990 for the prevention of bacterial endocarditis in individuals at risk for this disease. PARTICIPANTS: An ad hoc writing group appointed by the American Heart Association for their expertise in endocarditis and treatment with liaison members representing the American Dental Association, the Infectious Diseases Society of America, the American Academy of Pediatrics, and the American Society for Gastrointestinal Endoscopy. EVIDENCE: The recommendations in this article reflect analyses of relevant literature regarding procedure-related endocarditis, in vitro susceptibility data of pathogens causing endocarditis, results of prophylactic studies in animal models of endocarditis, and retrospective analyses of human endocarditis cases in terms of antibiotic prophylaxis usage patterns and apparent prophylaxis failures. MEDLINE database searches from 1936 through 1996 were done using the root words endocarditis, bacteremia, and antibiotic prophylaxis. Recommendations in this document fall into evidence level III of the US Preventive Services Task Force categories of evidence. CONSENSUS PROCESS: The recommendations were formulated by the writing group after specific therapeutic regimens were discussed. The consensus statement was subsequently reviewed by outside experts not affiliated with the writing group and by the Science Advisory and Coordinating Committee of the American Heart Association. These guidelines are meant to aid practitioners but are not intended as the standard of care or as a substitute for clinical judgment. CONCLUSIONS: Major changes in the updated recommendations include the following: (1) emphasis that most cases of endocarditis are not attributable to an invasive procedure; (2) cardiac conditions are stratified into high-, moderate-, and negligible-risk categories based on potential outcome if endocarditis develops; (3) procedures that may cause bacteremia and for which prophylaxis is recommended are more clearly specified; (4) an algorithm was developed to more clearly define when prophylaxis is recommended for patients with mitral valve prolapse; (5) for oral or dental procedures the initial amoxicillin dose is reduced to 2 g, a follow-up antibiotic dose is no longer recommended, erythromycin is no longer recommended for penicillin-allergic individuals, but clindamycin and other alternatives are offered; and (6) for gastrointestinal or genitourinary procedures, the prophylactic regimens have been simplified. These changes were instituted to more clearly define when prophylaxis is or is not recommended, improve practitioner and patient compliance, reduce cost and potential gastrointestinal adverse effects, and approach more uniform worldwide recommendations.

Prevention of bacterial endocarditis. Recommendations by the American Heart Association.

OBJECTIVE: To update recommendations issued by the American Heart Association last published in 1990 for the prevention of bacterial endocarditis in individuals at risk for this disease. PARTICIPANTS: An ad hoc writing group appointed by the American Heart Association for their expertise in endocarditis and treatment with liaison members representing the American Dental Association, the Infectious Diseases Society of America, the American Academy of Pediatrics, and the American Society for Gastrointestinal Endoscopy. EVIDENCE: The recommendations in this article reflect analyses of relevant literature regarding procedure-related endocarditis, in vitro susceptibility data of pathogens causing endocarditis, results of prophylactic studies in animal models of endocarditis, and retrospective analyses of human endocarditis cases in terms of antibiotic prophylaxis usage patterns and apparent prophylaxis failures. MEDLINE database searches from 1936 through 1996 were done using the root words endocarditis, bacteremia, and antibiotic prophylaxis. Recommendations in this document fall into evidence level III of the US Preventive Services Task Force categories of evidence. CONSENSUS PROCESS: The recommendations were formulated by the writing group after specific therapeutic regimens were discussed. The consensus statement was subsequently reviewed by outside experts not affiliated with the writing group and by the Science Advisory and Coordinating Committee of the American Heart Association. These guidelines are meant to aid practitioners but are not intended as the standard of care or as a substitute for clinical judgment. CONCLUSIONS: Major changes in the updated recommendations include the following: (1) emphasis that most cases of endocarditis are not attributable to an invasive procedure; (2) cardiac conditions are stratified into high-, moderate-, and negligible-risk categories based on potential outcome if endocarditis develops; (3) procedures that may cause bacteremia and for which prophylaxis is recommended are more clearly specified; (4) an algorithm was developed to more clearly define when prophylaxis is recommended for patients with mitral valve prolapse; (5) for oral or dental procedures the initial amoxicillin dose is reduced to 2 g, a follow-up antibiotic dose is no longer recommended, erythromycin is no longer recommended for penicillin-allergic individuals, but clindamycin and other alternatives are offered; and (6) for gastrointestinal or genitourinary procedures, the prophylactic regimens have been simplified. These changes were instituted to more clearly define when prophylaxis is or is not recommended, improve practitioner and patient compliance, reduce cost and potential gastrointestinal adverse effects, and approach more uniform worldwide recommendations.

Use of electrophoretic karyotyping in the evaluation of Candida infections in a neonatal intensive-care unit.

OBJECTIVE: To evaluate a possible common-source outbreak of Candida infections in the neonatal intensive-care unit. Systemic Candida infections increased from 6 to 11 cases (0.71 to 1.34 per 1,000 patient-days). In addition, Candida parapsilosis infections increased from 1 in 1992 to 10 in 1993. DESIGN AND SETTING: Tertiary-care, teaching, pediatric institution with a 40-bed neonatal intensive-care unit (NICU). Clinical characteristics, associated conditions, and antimicrobial therapy were obtained from the medical records of all NICU patients with positive blood cultures for Candida during 1992 and 1993. Nineteen Candida isolates from 15 infants were studied retrospectively using contour-clamped homogeneous electric-field (CHEF) electrophoresis. RESULTS: CHEF revealed eight karyotypes of C parapsilosis. Five isolates recovered from four patients shared one karyotype. The remaining isolates from seven infants all had distinctly different karyotypes. CONCLUSIONS: The evidence was insufficient to implicate a single source of infection, even though four patients in the same unit had identical strain types. However, identical strains of C parapsilosis were associated geographically, suggesting that nosocomial acquisition of C parapsilosis through indirect patient contact in the NICU was possible. The CHEF technique yields unique patterns that may be used to delineate clinical isolates and to study the molecular epidemiology of candidal infections.

Prevention of bacterial endocarditis: recommendations by the American Heart Association.

OBJECTIVE: To update recommendations issued by the American Heart Association last published in 1990 for the prevention of bacterial endocarditis in individuals at risk for this disease. PARTICIPANTS: An ad hoc writing group appointed by the American Heart Association for their expertise in endocarditis and treatment with liaison members representing the American Dental Association, the Infectious Diseases Society of America, the American Academy of Pediatrics, and the American Society for Gastrointestinal Endoscopy. EVIDENCE: The recommendations in this article reflect analyses of relevant literature regarding procedure-related endocarditis, in vitro susceptibility data of pathogens causing endocarditis, results of prophylactic studies in animal models of endocarditis, and retrospective analyses of human endocarditis cases in terms of antibiotic prophylaxis usage patterns and apparent prophylaxis failures. MEDLINE database searches from 1936 through 1996 were done using the root words endocarditis, bacteremia, and antibiotic prophylaxis. Recommendations in this document fall into evidence level III of the US Preventive Services Task Force categories of evidence. CONSENSUS PROCESS: The recommendations were formulated by the writing group after specific therapeutic regimens were discussed. The consensus statement was subsequently reviewed by outside experts not affiliated with the writing group and by the Science Advisory and Coordinating Committee of the American Heart Association. These guidelines are meant to aid practitioners but are not intended as the standard of care or as a substitute for clinical judgment. CONCLUSIONS: Major changes in the updated recommendations include the following: (1) emphasis that most cases of endocarditis are not attributable to an invasive procedure; (2) cardiac conditions are stratified into high-, moderate-, and negligible-risk categories based on potential outcome if endocarditis develops; (3) procedures that may cause bacteremia and for which prophylaxis is recommended are more clearly specified; (4) an algorithm was developed to more clearly define when prophylaxis is recommended for patients with mitral valve prolapse; (5) for oral or dental procedures the initial amoxicillin dose is reduced to 2 g, a follow-up antibiotic dose is no longer recommended, erythromycin is no longer recommended for penicillin-allergic individuals, but clindamycin and other alternatives are offered; and (6) for gastrointestinal or genitourinary procedures, the prophylactic regimens have been simplified. These changes were instituted to more clearly define when prophylaxis is or is not recommended, improve practitioner and patient compliance, reduce cost and potential gastrointestinal adverse effects, and approach more uniform worldwide recommendations.

Seroprevalence of antibody against poliovirus in inner-city preschool children. Implications for vaccination policy in the United States.

OBJECTIVES: To assess susceptibility to poliomyelitis in selected inner-city preschool children in the United States and to estimate the contribution of secondary spread of live attenuated oral poliovirus vaccine virus to type-specific immunity. DESIGN: Cross-sectional seroprevalence study. METHODS: Serum neutralizing antibody levels against poliovirus types 1, 2, and 3 were analyzed according to vaccination status, age, and other sociodemographic variables. SETTING: Hospital and satellite clinics serving inner-city populations in Houston, Tex, and Detroit, Mich, 1990 to 1991. PARTICIPANTS: A total of 526 children aged 12 to 47 months seeking medical care were enrolled in the seroprevalence study; 144 children aged 12 to 35 months without a history of previous oral poliovirus vaccination were enrolled in the secondary spread study. RESULTS: Seropositive rates were similar in children in both cities, ranging from about 80% for types 1 and 3 in 12- to 23-month-old children to more than 90% in those aged 36 to 47 months. The most important predictor of seropositivity was the number of doses of oral poliovirus vaccine received (P < .01), with levels approximately 90% for all 3 serotypes among children who had received 3 or more doses. In children likely to have been unvaccinated, seropositive rates ranged from 9% to 18% for poliovirus types 1 and 3 and from 29% to 42% for type 2; secondary spread of vaccine virus appeared to have occurred among children who had previously received 1 dose or less but not those with 2 or more doses. CONCLUSIONS: Levels of immunity to poliovirus among inner-city preschoolers are high and may be predicted by the number of doses of oral poliovirus vaccine received. Secondary spread of the vaccine virus plays a modest role in increasing polio immunity in inner-city populations, especially against types 1 and 3. This role will decrease in importance if the recently attained high levels of immunization coverage in the United States are sustained and if the risk of importation of wild poliovirus continues to diminish.

Adherence to physicians' instructions as a factor in managing streptococcal pharyngitis.

Adherence to physicians' instructions, including taking medications as prescribed, is essential for the proper treatment of streptococcal pharyngitis and the prevention of rheumatic fever. Nonadherence can be in many forms, including failure to have prescriptions filled, omission of doses, errors in dosing or administration time, and premature discontinuation of medication. Adherence is dependent on the physician, the patient, the illness, and the medication. Proper communication by the physician and prescribing inexpensive medications that can be taken once or twice daily are simple, yet important actions that improve adherence.

Relationship of MICs to efficacy of cefotaxime in treatment of Streptococcus pneumoniae infections.

In June 1993, the National Committee for Clinical Laboratory Standards (NCCLS) recommended stringent new interpretive guidelines for antibiotics indicated for Streptococcus pneumoniae meningitis. To assess the predictive values of the recommended breakpoints, retrospective data were collected from patients who had S. pneumoniae infections and were treated with cefotaxime monotherapy. Susceptibilities based on the NCCLS interpretative categories were compared with clinical and bacteriologic outcomes. In 76 evaluable patients, the most common infections were bacteremia-septicemia (n = 49), meningitis (n = 37), and lower respiratory tract infection (n = 14). Under the NCCLS breakpoints proposed in 1993, 55 isolates would have been classed as susceptible to cefotaxime (MIC, < or = 0.25 microgram/ml), 18 would have been classed as intermediate (MIC, 0.5 to 1.0 microgram/ml), and 2 would have been classed as resistant (MIC, > or = 2 micrograms/ml). Of 75 cefotaxime-treated patients for whom cefotaxime MICs were recorded, 73 were clinically cured or improved (37 of 37 with meningitis and 36 of 38 with other infections). One case of bacteremia and one case of bone-and-joint infection were scored as therapeutic failures because initial monotherapy had to be modified because of an adverse drug reaction. Excluding these patients, there were 18 patients infected with S. pneumoniae that would have been classed as not fully susceptible (i.e., MICs > or = 0.5 microgram/ml); all of these patients were cured or improved. The results of this analysis demonstrate that successful treatment with cefotaxime did not correlate well with the guidelines for the susceptibility of pneumococcal isolates to either penicillin or cefotaxime established by the 1993 NCCLS breakpoint recommendations. Because of this study and other similar findings, the NCCLS adopted more clinically relevant guidelines in 1994.

Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci, and HACEK microorganisms. American Heart Association.

OBJECTIVE: To provide guidelines for the treatment of endocarditis in adults caused by the following microorganisms: viridans streptococci and other streptococci, enterococci, staphylococci, and fastidious gram-negative bacilli of the HACEK group. PARTICIPANTS: An ad hoc writing group appointed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young. EVIDENCE: Published studies of the treatment of patients with endocarditis and the collective clinical experience of this group of experts. CONSENSUS PROCESS: The recommendations were formulated during meetings of the working group and were prepared by a writing committee after the group had agreed on the specific therapeutic regimens. The consensus statement was subsequently reviewed by standing committees of the American Heart Association and by a group of experts not affiliated with the working group. CONCLUSIONS: Sufficient evidence has been published that recommendations regarding treatment of the most common microbiological causes of endocarditis (viridans streptococci, enterococci, Streptococcus bovis, staphylococci, and the HACEK organisms) are justified. There are insufficient published data to make a strong statement regarding the efficacy of specific therapeutic regimens for cases of endocarditis due to microorganisms that uncommonly cause endocarditis. As a useful aid to the practicing clinician, the writing group developed a consensus opinion regarding management of endocarditis caused by the most commonly encountered microorganisms and regarding those cases due to infrequent causes of endocarditis.

Cefotaxime use in pediatric infections.

Cefotaxime has been used extensively in many pediatric centers in the United States for the past 10 or more years. Its main usage has been for the treatment of various serious bacterial infections in pediatric patients, primarily meningitis and sepsis. It has also been used to treat intraabdominal, urinary tract, soft tissue, bone, and joint infections. Although there has been a marked reduction in the incidence of invasive Haemophilus influenzae type b infections following the introduction of effective vaccines, cefotaxime remains very useful against the other common pathogens causing serious infections in pediatric patients. The increasing number of pneumococci resistant to penicillin and third-generation cephalosporins has created a new challenge for the management of serious pneumococcal infections. In many institutions, cephalosporins in general have been overused and abused, resulting in the emergence of resistant organisms and an increasing burden on resources. The judicious use of cefotaxime and other cephalosporins should be emphasized.