Intravenous antibiotic regimens and prophylaxis of odontogenic bacteraemia.

OBJECTIVES: This study retrospectively examines the efficacy of prophylactic intravenous antibiotic regimens in the prevention of odontogenic bacteraemia in children with severe congenital heart defects receiving comprehensive dental treatment under general anaesthesia. PATIENTS AND METHODS: Blood cultures were taken from children with congenital cardiac defects 30 seconds after completion of dental treatment under general anaesthesia. Antibiotic prophylaxis had been given intravenously immediately before dental treatment. The choice of antibiotics and the extent of dental treatment were recorded. The percentage prevalence of bacteraemia was compared with published data following multiple dental extractions using the same clinical and microbiological methodology. RESULTS: The overall percentage prevalence of positive cultures in children receiving intravenous prophylactic antibiotics was 16%. The percentage of positive blood cultures in cardiac children who received ampicillin alone was not significantly different from that in children having a combination of amikacin and teicoplanin (16.7% v 22.2%) respectively [Chi Square = 0.385, df = 1, P= 0.535]. When compared with multiple extractions, both ampicillin alone and amikacin with teicoplanin were effective in reducing the prevalence of odontogenic bacteraemia. CONCLUSIONS: In children with cardiac defects, bacteraemia after dental treatment is reduced by antibiotics but is still detected on 16% of occasions. In comparison with children receiving ampicillin alone, the combination of amikacin and teicoplanin is as effective in reducing bacteraemia in children who are either allergic to penicillins or who have received them within the previous month.

Tuberculosis of the central nervous system in children: a 20-year survey.

OBJECTIVE: To review our experience of central nervous system (CNS) tuberculosis at a major British paediatric tertiary referral centre, following the introduction of CT Scan facilities. METHODS: This was a retrospective case survey (prospective in nine patients) of patients admitted to Great Ormond Street over a 20-year period (1977-1997), who fulfilled criteria for a diagnosis of CNS tuberculosis. Data were collected with regard to the clinical, laboratory and demographic characteristics of patients, as well as results of radiological investigations and data on clinical outcome. RESULTS: We identified 38 children with CNS tuberculosis: 23 with tuberculous meningitis (TBM), 10 with tuberculous meningitis and associated tuberculomas and five with tuberculomas alone. The mean age of this group was 3.7 years, ranging from 8 months to 16 years. Only 14 (37%) were of Caucasian origin. A contact source was identified in 18 patients (47%). Previous BCG had only been given to six (16%). The main clinical symptoms and signs present on admission were alteration in consciousness in 30 patients (79%), focal neurological signs in 25 (66%) and fever in 25 (66%). Seizures were observed in 20 patients (53%) and meningism in 18 (47%). Mycobacterium tuberculosis was either cultured or identified by acid-fast stain from CSF or brain tissue from 24 patients (63%). The Mantoux reaction was positive in 17/33 (51%); abnormalities of the chest X-ray were found in 15 (40%). Cranial CT scans of the patients presenting with TBM showed hydrocephalus in 31 patients (94%), and basilar enhancement in 27 (93%) out of the 29 patients who received intravenous contrast. Anti-tuberculous therapy administered varied according to current recommendations of the period; concurrent steroids were given to 31 patients (82%). Neurosurgical procedures were required in the majority of patients with TBM, 25 (76%). In five patients with TBM, new tuberculoma developed during treatment. The overall mortality for our group of patients was 13%, whilst permanent neurological sequelae were seen in 47% of the patients. None of the patients who received BCG either died or had severe sequelae. Mortality and morbidity rates were higher in the first 10 years of the study and amongst those patients admitted in Stage III disease. CONCLUSIONS: CNS tuberculosis continues to be a condition which carries significant morbidity and mortality. Early diagnosis and prompt initiation of treatment are essential to improve the poor outcome.

Bactericidal activity against coagulase-negative staphylococci is impaired in infants receiving long-term parenteral nutrition.

OBJECTIVE: To examine the role of total parenteral nutrition (TPN) in predisposing infants to infection caused by coagulase-negative staphylococci. SUMMARY BACKGROUND DATA: Total parenteral nutrition is an important means of providing essential nutrients to newborn infants. However, its use has been associated with complications, particularly infection caused by coagulase-negative staphylococci. Recent data suggest that TPN may modulate immune function; however, reports directly indicating impaired immunity against coagulase-negative staphylococci during TPN are limited. METHODS: Study 1 involved 31 infants younger than 4 months who had undergone surgery and were not receiving antibiotics; 20 were receiving TPN and 11 were receiving a normal enteral diet. An in vitro whole blood model was used to measure the host bactericidal activity against coagulase-negative staphylococci. Bacterial killing and phagocytosis were measured after a 45-minute challenge with viable coagulase-negative staphylococci. In study 2, whole blood killing and intracellular killing of coagulase-negative staphylococci were measured in five newborn infants (younger than 2 months) who were receiving long-term TPN (>10 days), five control infants receiving a normal enteral diet, and five healthy adults. RESULTS: In study 1, infants receiving a normal enteral diet showed a high capacity to ingest and kill coagulase-negative staphylococci. In contrast, the blood of infants receiving long-term TPN showed a reduction in coagulase-negative staphylococci phagocytosis and killing. There were significant negative linear correlations between the duration of TPN and killing of coagulase-negative staphylococci and phagocytosis of coagulase-negative staphylococci. In study 2, infants receiving long-term TPN had lower whole blood killing and intracellular killing than infants receiving a normal enteral diet and healthy adult volunteers. These data seem to indicate a neutrophil dysfunction mediated by TPN in infancy. CONCLUSIONS: Host defense mechanisms, including phagocytosis and killing of coagulase-negative staphylococci, are impaired during long-term TPN. The impaired bactericidal activity seems to be related to defective intracellular killing in neutrophils. These findings may explain the high rate of septicemia caused by coagulase-negative staphylococci in infants receiving TPN.

Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement deposition.

Mannose-binding lectin (MBL) is a collagenous serum lectin believed to be of importance in innate immunity. Genetically determined low levels of the protein are known to predispose to infections. In this study the binding of purified MBL to pathogens isolated from immunocompromised children was investigated by flow cytometry. Diverse Candida species, Aspergillus fumigatus, Staphylococcus aureus, and beta-hemolytic group A streptococci exhibited strong binding of MBL, whereas Escherichia coli, Klebsiella species, and Haemophilus influenzae type b were characterized by heterogeneous binding patterns. In contrast, beta-hemolytic group B streptococci, Streptococcus pneumoniae, and Staphylococcus epidermidis showed low levels of binding. Bound MBL was able to promote C4 deposition in a concentration-dependent manner. We conclude that MBL may be of importance in first-line immune defense against several important pathogens.

Safety and tolerability of fluconazole in children.

The safety profile of fluconazole was assessed for 562 children (ages, 0 to 17 years) comprising 323 males and 239 females. The data are derived from 12 clinical studies of fluconazole as prophylaxis or treatment for a variety of fungal infections in predominantly immunocompromised patients. Most children received multiple doses of fluconazole in the range of 1 to 12 mg/kg of body weight; a few received single doses. Administration was mainly by oral suspension or intravenous injection. Overall, 58 (10.3%) children reported 80 treatment-related side effects. The most common side effects were associated with the gastrointestinal tract (7.7%) or skin (1.2%). Self-limiting, treatment-related side effects affecting the liver and biliary system were reported in three patients (0.5%). Overall, 18 patients (3.2%) discontinued treatment due to side effects, mainly gastrointestinal symptoms. Dose and age did not appear to influence the incidence and pattern of side effects. Treatment-related laboratory abnormalities were uncommon, the most frequent being transient elevated alanine aminotransferase (4.9%), aspartate aminotransferase (2.7%), and alkaline phosphatase (2.3%) levels. Although 98.6% of patients were taking concomitant medications, no clinical or laboratory interactions were observed. The safety profile of fluconazole was compared with those of other antifungal agents, mostly oral polyenes, by using a subset of data from five controlled studies. Side effects were reported by more patients treated with fluconazole (45 of 382; 11.8%) than by those patients treated with comparable agents (25 of 381; 6.6%); vomiting and diarrhea were the most common events in both groups. The incidence and type of treatment-related laboratory abnormalities were similar for the two groups. In conclusion, fluconazole was well tolerated by the pediatric population, many of whom were suffering from severe underlying disease and were taking a variety of concurrent medications. The safety profile of fluconazole in children mirrors the excellent safety profile seen in adults.

Application of electronmicroscopy, enzyme immunoassay, and RT-PCR to monitor an outbreak of astrovirus type 1 in a paediatric bone marrow transplant unit.

During 1997, an extensive outbreak of astrovirus occurred in a unit where paediatric patients were being treated for leukaemias and inherited immune deficiency disorders. Prolonged shedding of virus for many months following infection was demonstrated in three patients who had undergone bone marrow transplantation. Comparison of reverse transcription-polymerase chain reaction (RT-PCR), enzyme immunoassay (EIA), and electronmicroscopy (EM) to monitor the outbreak showed that many subclinical infections, mainly in children aged > 3 years could only be detected by RT-PCR. Use of RT-PCR revealed that several patients were infected earlier and shed virus for longer than by using EM or EIA. The virus responsible for the outbreak was identified as HAstV-1 and was shown to have a sequence that differed from a strain obtained in 1988.

Rhizopus microsporus in wooden tongue depressors: a major threat or minor inconvenience?

The investigation and management of an apparent outbreak of Rhizopus spp. in a London paediatric referral centre between September 1995 and April 1996 is described. The organism was identified in microbiological surveillance samples from 23 patients nursed in four hospital areas. Investigations revealed the presence of the organism in spatulae from all ward areas investigated and from closed boxed containers held in the central hospital stores obtained from a new supplier. In contrast, culture of spatulae from the initial supplier failed to yield any fungal isolates. The incident was reported to the Medical Device Agency (MDA), the Central Public Health Laboratory Service (CPHLS) and the Birmingham PHLS. A statement was prepared for the weekly Communicable Disease Report and a hazard warning issued by the MDA. The spatulae were withdrawn from use and the contract with the original supplier was re-established. This incident resulted in contamination of samples only and no patient involvement. It highlights the problems which may follow use of equipment for unintended purposes and the need for good manufacturing practice guidelines to be applied to non-sterile equipment used in direct patient care.

Dental bacteremia in children.

Bacteremia resulting from dental extraction is regarded as an important cause of bacterial endocarditis, and it is therefore recommended that patients undergoing tooth extraction be given prophylactic antibiotics. As dental procedures other than extractions may also cause bacteremias, we studied a variety of dental procedures routinely used in pediatric dentistry. Blood samples for cultures were obtained 30 s after each of 13 dental operative procedures in 735 anesthetized children aged 2-16 years. Four procedures used for conservative dentistry caused bacteremias significantly more often than the baseline value of 9.4%: polishing teeth 24.5%, intraligamental injection 96.6%, rubber dam placement 29.4%, and matrix band with wedge placement 32.1%. In comparison, toothbrushing alone caused a bacteremia on 38.5% of occasions. The organisms isolated were typical of odontogenic bacteremias in that 50% of the isolates were identified as varieties of viridans streptococci. These data show that a wider variety of dental procedures than was previously documented cause bacteremia.

Affinity of antigen-specific IgG distinguishes multiple sclerosis from encephalitis.

The characteristics of antigen-specific IgG in patients with multiple sclerosis and patients with encephalitis have been compared. Both groups of patients showed antigen-specific oligoclonal bands locally synthesised in the CSF. When the affinity distribution of the antigen-specific IgG was measured there was a marked difference between the two groups. Encephalitis patients had high affinity antibody against the causative antigen. This was consistent with the antibody undergoing affinity maturation as a result of the immune system fighting a primary infection. Multiple sclerosis patients lacked high affinity response. This lack of high affinity antibody was also seen in those encephalitis patients when antigens other than the causative antigen were studied.

Septicaemia in paediatric intensive-care patients at the Hospital for Sick Children, Great Ormond Street.

A review of nosocomial septicaemia in paediatric intensive care in a tertiary referral setting was undertaken for a 33-month period (1988-90). This involved six units: Cardiothoracic surgery; Neonatal surgery; general medical; Renal dialysis/transplant; Haematology/Oncology and Infectious disease/Immunology. The latter two units undertake bone marrow transplantation. During the study period, 10,719 admissions were made to these areas and 624 episodes of septicaemia were documented in 464 children. The frequency of septicaemia per 100 admissions ranged from 1.5 in the Renal Transplant Unit to 17.3 in the Haematology/Oncology unit. Over 60% of all septicaemic episodes occurred in children in the Haematology/Oncology and Cardiac Units. Gram-positive organisms were responsible for 66% of episodes, Gram-negative organisms for 17% and fungi for 3%. Polymicrobial episodes accounted for 13%. Coagulase-negative staphylococci were the most frequent isolates overall (43% of episodes in pure culture, and a further 6% in combination with other organisms). Staphylococcus aureus was associated with 10% of episodes, Enterobacteriaceae with 9% and Pseudomonas spp. 6% among which environmental pseudomonads predominated. Anaerobes and Haemophilus influenzae were each isolated in less than 1% of episodes.