Vancomycin and ceftazidime bioactivities persist for at least 2 weeks in the lumen in ports: simplifying treatment of port-associated bloodstream infections by using the antibiotic lock technique.

The residual antibiotic concentration of vancomycin (2 mg/ml)- or ceftazidime (2 mg/ml)-heparin solutions instilled in ports in pediatric hematology-oncology patients 1 to 34 days earlier was measured. Antibiotic concentrations of > or = 100 microg of either antibiotic per ml persisted for at least 21 days. For treatment of lumenal port infections, antibiotic-heparin dwell times of > or = 2 weeks may be appropriate.

Pneumococcal vaccine.

Streptococcus pneumoniae or pneumococcus is a major pathogen causing meningitis, pneumonia, other invasive infections, and the common infections acute otitis media and sinusitis. The major virulence factor is the polysaccharide capsule, present as one of approximately 90 serotypes. Anticapsular antibodies protect against infection. In 1977 and 1997, vaccines composed of purified capsular polysaccharide from 14- and 23-capsular types, respectively, were licensed for use in those children 2 years of age or older who are at increased risk for invasive pneumococcal infection. These vaccines have limited immunogenicity in infants and young children. Pneumococcal conjugate vaccines in which capsular polysaccharides from a limited number of serotypes are covalently linked to a protein carrier have recently been developed. In preliminary reports of randomized, double-blind control studies, a heptavalent vaccine administered as a series of infections to normal infants was efficacious in the prevention of invasive infections, episodes of lobar pneumonia, and acute otitis media caused by vaccine serotypes.

Cure of implantable venous port-associated bloodstream infections in pediatric hematology-oncology patients without catheter removal.

The efficacy of antibiotic treatment of port-associated bloodstream infection without device removal has not been systematically studied. We analyzed the outcome of 43 consecutive port-associated bloodstream infections in pediatric hematology-oncology patients. Etiologies included Staphylococcus epidermidis (30) and Staphylococcus aureus (6). Antibiotics were given through the port for a median of 11 days. Four ports were removed within 72 hours. In 36 (92%) of the remaining 39 episodes, there was a response to antibiotic therapy (defervescence and negative blood culture). In 78% of episodes in which there was a response (excluding two in which the catheters were removed because of mechanical problems), the infections were cured without port removal. Two of the four relapses were cured with a second course of antibiotics. The cure rate was 92% for S. epidermidis infections and 67% for S. aureus infections. Thus, the majority of port-associated bloodstream infections in pediatric hematology-oncology patients can be cured without device removal.

Stability of antibiotics used for antibiotic-lock treatment of infections of implantable venous devices (ports).

Antibiotic-lock is a treatment for catheter-related bloodstream infections in which a solution containing heparin and an antibiotic dwells in the lumen of the catheter or port. We tested the stability of vancomycin, cefazolin, ticarcillin-clavulanic acid, ceftazidime, or ciprofloxacin combined with heparin after incubation in vitro at 25 or 37 degrees C for intervals of up to 10 days by bioassay. All the antibiotic solutions except ceftazidime retained >/=90% activity at both 25 and 37 degrees C. Thus, studies of antibiotic-heparin lock solutions with dwell times of up to 10 days are feasible.

Legionella pneumonia in neonates: a literature review.

It has recently been recognized that neonates may develop pneumonia as a result of Legionella pneumophila. The objective of this study is to characterize the epidemiology, risk factors, diagnosis, clinical features, and outcome of neonatal legionellosis. Review of the literature revealed nine cases of neonatal Legionella infection. Five neonates were term infants and four were preterm. Eight had potential risk factors such as prematurity, congenital heart disease, bronchopulmonary dysplasia, or corticosteroid therapy. Diagnosis was proven by culture in all cases. The main presentation was acute respiratory distress requiring mechanical ventilation. In six infants, the infection had a fatal outcome, including five who were not treated with erythromycin. All the cases were nosocomial, and environmental Legionella was documented in five cases. As has been noted in adults and children with Legionella, early recognition and institution of appropriate therapy are the most important determinants of the prognosis.

Emergence of Candida parapsilosis as the predominant species causing candidemia in children.

An increase in the rate of isolation of Candida parapsilosis, relative to other Candida species, in our children's hospital led us to analyze the clinical and epidemiological variables associated with candidemia. We sought to determine if these variables are different for patients infected with C. parapsilosis. All episodes of candidemia occurring over a 7-year period were analyzed retrospectively. Of 81 episodes in 80 patients, 35 (43%) were in neonates, and 46 (57%) were in nonneonates. C. parapsilosis was isolated in 40 episodes (49%). C. parapsilosis was significantly more likely than non-C. parapsilosis species to be associated with prematurity (P = .001), presence of a central venous catheter (P = .002), and use of total parenteral nutrition (P = .03). C. parapsilosis has emerged as the predominant species in our children's hospital. The mortality rate associated with candidemia in children is lower than previously reported and may be associated with the high rate of isolation of C. parapsilosis.

Relevance of the catheter hub as a portal for microorganisms causing catheter-related bloodstream infections.

Microorganisms causing vascular catheter-related sepsis gain access to the bloodstream through either the skin at the catheter insertion site or through the catheter hub. The catheter insertion site is probably the predominant portal for microorganisms in catheters in place for a short time, but the catheter hub may play an increasingly important role in infection in association with long-term catheters, particularly those that are subcutaneously tunneled. Although transient contamination of the catheter hub does not cause infection, certain microorganisms may migrate endoluminally and enter the bloodstream, causing bacteremia or fungemia.

Duration of tick attachment as a predictor of the risk of Lyme disease in an area in which Lyme disease is endemic.

Animal studies have shown an exponential increase in the risk of Borrelia burgdorferi infection after 48-72 h of deer tick attachment. Persons with tick bites were prospectively studied to determine if those with prolonged tick attachment constitute a high-risk group for infection. Ticks were identified, measured for engorgement, and assayed by polymerase chain reaction (PCR) for B. burgdorferi DNA. Duration of attachment was determined from the scutal index of engorgement. Of 316 submissions, 229 were deer ticks; 14% were positive by PCR. Paired sera and an intact tick for determination of duration of attachment were available for 105 subjects (109 bites). There were 4 human cases (3.7% of bites) of B. burgdorferi infection. The incidence was significantly higher for duration of attachment > or =72 h than for <72 h: 3 (20%) of 15 vs. 1 (1.1%) of 94 (P = .008; odds ratio, 23.3; 95% confidence interval, 2.2-242). PCR was an unreliable predictor of infection. Tick identification and measurement of engorgement can be used to identify a small, high-risk subset of persons who may benefit from antibiotic prophylaxis.

Meningococcemia.

Meningococcal infection is a contagious disease that is spread via the respiratory route through pharyngeal secretions. Clinical manifestations range from occult bacteremia to overwhelming septicemia or meningitis. Skin manifestations often develop and may be the first sign that leads to clinical suspicion of meningococcemia. Treatment consists of antibiotic therapy and supportive care, which may include aggressive fluid resuscitation, oxygen, ventilatory support, and inotropic support. The use of chemoprophylaxis and in certain circumstances vaccination are important in preventing secondary cases of meningococcal disease.

Randomized, double blind comparison of brand and generic antibiotic suspensions: I. A study of taste in adults.

BACKGROUND: A belief that brand oral liquid medications taste better than their generic counterparts may influence prescribing habits among pediatricians. METHODS: We undertook a prospective, randomized, double blinded, comparative evaluation of the taste of brand and generic erythromycin ethylsuccinate, cephalexin monohydrate, erythromycin ethylsuccinate/sulfisoxazole, penicillin V potassium and trimethoprim-sulfamethoxazole in 42 adult volunteers. Subjects tasted one class of brand and generic antibiotics and rated them according to smell, texture, taste and aftertaste. RESULTS: At least one generic preparation of cephalexin, erythromycin ethylsuccinate/sulfisoxazole and penicillin V potassium was rated equal in taste to the respective brand name products. However, brand erythromycin estolate and trimethoprim-sulfamethoxazole name brand suspensions rated significantly higher than the other products tested. CONCLUSIONS: Based on our results brand name oral antibiotic formulations do not necessarily taste better than their generic counterparts.

Randomized, double blind comparison of brand and generic antibiotic suspensions: II. A study of taste and compliance in children.

BACKGROUND: The taste of oral liquid medications influences compliance in children. Generic preparations are prescribed to reduce cost and may taste worse than brand name products. METHODS: This was a prospective, randomized, double blind, crossover trial of the differences in taste and compliance between brand and generic antibiotic suspensions in children 3 to 14 years of age. Verbal and visual assessment methods were used to assess taste, and compliance was measured by the amount of drug returned after use. RESULTS: Ten children in each of the cephalexin and erythromycin-sulfisoxazole groups did not report that the brand and generic formulations tasted differently. Fifteen children thought that brand trimethoprim-sulfamethoxazole tasted better than the generic preparation. CONCLUSIONS: Brand name oral liquid antibiotics do not necessarily taste better than their generic counterparts. Despite preference for the taste of brand trimethoprim-sulfamethoxazole, all of the children in this study were compliant with both brand and generic medications.

Characterization of vancomycin resistance in Enterococcus durans.

During investigation of an outbreak of vancomycin resistant Enterococcus faecium in a paediatric hospital, an isolate of Enterococcus durans resistant to vancomycin, teicoplanin, ampicillin and highly resistant to gentamicin and streptomycin was found in the stools of a patient also colonized with a strain of E. faecium with the same resistance pattern. Minimal inhibitory concentrations of vancomycin and teicoplanin were 512 and 64 mg/mL, respectively. Resistance to vancomycin as well as high-level resistance to gentamicin was transferable to an E. faecium recipient strain. Both multiresistant E. faecium and E. durans isolates as well as the transconjugant presented only one plasmid. The vanA gene was detected and localized to the high molecular weight plasmid by DNA hybridization with a vanA gene probe. Growth in vancomycin resulted in induction of an approximately 40 kDa protein visible in membrane preparations from these cells. Genetic linkage between vancomycin and gentamicin resistance genes in the same plasmid is suggested.

Role of the 145-kilodalton surface protein in virulence of the Brazilian purpuric fever clone of Haemophilus influenzae biogroup aegyptius for infant rats.

Brazilian purpuric fever (BPF) is a fulminant infection associated with bacteremia with clonally related strains of Haemophilus influenzae biogroup aegyptius. Case-associated clone strains are more virulent for infant rats than are non-BPF case-associated H. influenzae biogroup aegyptius isolates. I sought to determine the possible role of P145, a 145-kDa surface protein of BPF case H. influenzae biogroup aegyptius clone isolates, in virulence. First, I compared the virulence of two case-associated clone isolates from the blood of children with BPF from Serrana, Brazil, which differed in P145 expression but were identical in all other phenotypic and genotypic characteristics studied. Twenty-four hours after intraperitoneal inoculation of infant rats, there was a significantly higher incidence (51 versus 26%; P = 0.035) and magnitude (2.9 +/- 5.8 versus 0.7 +/- 2.0 CFU/0.01 ml; P = 0.024) of bacteremia in rats inoculated with the P145-expressing strain. I next compared the virulence of a P145-expressing case-associated clone strain with two P145-nonexpressing phase variants of this strain. One variant exhibited a lower mean magnitude of bacteremia and one displayed a similar magnitude of bacteremia compared with that displayed the P145-expressing parental strain. P145-expressing revertants of the P145-nonexpressing strains exhibited the same virulence as the P145-negative variants from which they were derived. Colonies grown from blood cultures maintained the P145 phenotype of the inoculated strain. These results suggest that P145 expression does not contribute to the virulence of the BPF case clone strain for infant rats following intraperitoneal inoculation.

Synergy between protamine and vancomycin in the treatment of Staphylococcus epidermidis biofilms.

OBJECTIVES: To test for synergy between protamine and vancomycin by analyzing their bactericidal activities against slime-producing Staphylococcus epidermidis ATCC 35983 under planktonic and biofilm conditions. METHODS: We evaluated the activity of vancomycin and protamine separately against planktonic S epidermidis in broth by measuring the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for each agent according to the standard macrobroth dilution method. To assess the possibility of synergy between these two agents, planktonic S epidermidis was exposed to vancomycin and protamine together in varying concentrations. Biofilms containing S epidermidis were then prepared and subjected to incubation with vancomycin and protamine separately as well as combined in varying concentrations. The bacterial viability of S epidermidis in the planktonic and biofilm phases after exposure to these two agents was assessed by qualitative culture and determination of viable colony blots. RESULTS: Standard antibacterial susceptibility tests revealed that the MICs of protamine and vancomycin were 1 and 2 micrograms/mL, respectively, and their MBCs were 4 micrograms/mL. The MICs were unchanged when protamine and vancomycin were combined in varying concentrations. Neither agent exhibited significant bactericidal activity against S epidermidis in the biofilm phase at concentrations < or = 32 micrograms/mL. However, a combination of both agents, each at 32 micrograms/mL, resulted in a 7-log decrease in viable bacterial counts. CONCLUSIONS: Protamine alone exhibited significant antibacterial activity against planktonic S epidermidis. No synergy was noted between protamine and vancomycin against S epidermidis in the planktonic phase. However, synergy was demonstrated when a combination of protamine and vancomycin was used on S epidermidis in the biofilm phase. Thus, protamine shows promise as an adjunctive agent to vancomycin in the treatment of S epidermidis in biofilms.

Phase-variable expression of the 145-kDa surface protein of Brazilian purpuric fever case-clone strains of Haemophilus influenzae biogroup aegyptius.

Clonally related strains of Haemophilus influenzae biogroup aegyptius have recently been associated with Brazilian purpuric fever (BPF). Antibodies to a 145-kDa minor outer membrane protein (P145) are bactericidal and protect against experimental bacteremia. To determine if P145 is conserved among case-clone strains, case-clone strains were screened for P145 expression. Assays of a large number of colonies of each strain using colony immunoblot revealed colonies reactive with anti-P145 sera in all 17 case-clone strains. P145 was expressed at a low frequency (0.08%-2.2% of colonies) in 14 strains and at a high frequency (> 98%) in 3 strains. Expression of P145 by reactive colonies was confirmed by SDS-PAGE. Also, anti-P145-nonreactive variant colonies of P145-expressing strains were detected in 0.4%-1.5% of colonies. These findings indicate P145 is conserved among BPF case-clone strains and is subject to phase-variable expression.

Intravenous catheter-related infections.

Vascular catheter-related infection is an important cause of mortality and morbidity in hospitalized patients. The mean incidence of catheter-related bloodstream infection in hospitalized pediatric patients is 2.4 episodes per 1,000 days. Totally implantable central venous catheters may be associated with a lower risk of infection. Coagulase-negative staphylococci are the predominant cause and account for about one third of episodes of catheter-related bloodstream infection. The diagnosis of catheter-related bloodstream infection is often difficult because there are frequently no signs of inflammation around the catheter. Diagnosis depends on either a positive quantitative catheter culture yielding the same microorganism recovered from the bloodstream or differential quantitative blood cultures with significantly greater colony counts from blood drawn through the catheter than from blood drawn through a peripheral vein. Alternatively, probably catheter-related sepsis can be diagnosed when clinical sepsis is refractory to antimicrobial therapy but responds to catheter removal. Often these criteria are not met but catheter-related bloodstream infection is presumed because a common skin microorganism is isolated from the blood when clinical manifestations of bloodstream infection are present and there is no other apparent source of infection. Microorganisms causing catheter-related bloodstream infection gain access to the bloodstream predominantly from either the catheter insertion site or the catheter hub. Most catheter-related infections occurring shortly after catheter insertion probably gain access to the bloodstream by extraluminal migration along the catheter from the skin at the catheter insertion site. When catheters are in place for extended periods, especially greater than 30 days, the catheter hub probably plays a major role in microorganisms gaining access and then migrating endoluminally until reaching the bloodstream. Recently employed strategies for the prevention of catheter-related infections include topical antibiotics or antiseptics at the catheter insertion site, flush solutions containing vancomycin, and bonding antimicrobial agents to the catheter. Infection of peripheral and central venous catheters generally resolves after catheter removal. For tunneled silicone catheters, most episodes of catheter-related infection can be initially managed with antimicrobial therapy infused through the catheter without catheter removal. Staphylococcus aureus is generally more aggressive and associated with more complications than coagulase-negative staphylococci. Microorganisms that usually require catheter removal include Candida and Bacillus species. Adjunctive treatments of catheter infections include the use of urokinase. Catheter-related infection remains an important complication of vascular access. Novel prevention and treatment strategies are currently being investigated. In the near future bonding of antibiotics or other agents to catheters may become routine.(ABSTRACT TRUNCATED AT 400 WORDS)