Macrolides in the management of streptococcal pharyngitis/tonsillitis.

The most frequent bacterial cause of pharyngitis/tonsillitis, a common infection in children, is group A beta-hemolytic streptococci. Prevention of acute rheumatic fever is the principal goal of treatment, although antibiotic therapy may also relieve the signs and symptoms of infection, shorten the infective period and prevent suppurative complications. Penicillin is the drug of choice. Alternatives are required, however, for patients allergic to penicillin and may be needed if the rate of bacteriologic failure with penicillin observed during the past decade continues. Erythromycin is generally effective in this infection, but its use, especially in children, is complicated by the need for multiple daily doses, a lengthy treatment period and a high rate of gastrointestinal side effects. The newer macrolides clarithromycin and azithromycin offer lower rates of gastrointestinal complaints and more convenient dosing. Clarithromycin is recommended for twice daily and azithromycin for once daily administration. Because of its prolonged tissue half-life, the recommended duration of azithromycin therapy is 5 days, compared with 10 days for penicillin, erythromycin and clarithromycin. Newer macrolides are rational alternatives to erythromycin for streptococcal pharyngitis/tonsillitis in penicillin-allergic patients.

Future indications for macrolides.

The antimicrobial spectrum of azithromycin and clarithromycin suggests a number of further uses for these newer macrolides. Favorable clinical and bacteriologic responses have been reported with both antibiotics in children with community-acquired pneumonia. Response rates were high for overall patient populations and for subgroups with infection caused by Mycoplasma pneumoniae and Chlamydia pneumoniae. Treatment with azithromycin or clarithromycin has resulted in a reduction in mycobacteremia and an improvement in clinical symptoms in adult AIDS patients with disseminated Mycobacterium avium-intracellulare complex. Prophylactic treatment with azithromycin may prevent M. avium-intracellulare complex, especially when combined with rifabutin. Preliminary evidence suggests that both azithromycin and clarithromycin in multidrug combinations may effectively eradicate Helicobacter pylori and that azithromycin may be useful in treating bacterial gastritis caused by Campylobacter species. Trachoma and infections caused by Bordetella pertussis and Ureaplasma urealyticum are other possible future indications for the newer macrolides. Limited clinical evidence also suggests that azithromycin may be effective in the prevention and treatment of malaria.

Chickenpox in childhood. A review prepared for the UK Advisory Group on Chickenpox on behalf of the British Society for the Study of Infection.

Chickenpox in childhood is a milder condition than in older patients, but serious and even fatal complications may occur. These occur especially in immunosuppressed individuals, but can also be seen in normal children. The commonest of these is secondary bacterial infection with staphylococci or streptococci. Reye's syndrome is now rare in chickenpox, since aspirin no longer used in treatment. Aciclovir and VZIG (varicella zoster immune globulin) have a role in the management of chickenpox in the immunosuppressed or immunodeficient child, and aciclovir may be valuable in managing some normal children. Chickenpox should not always be considered a trivial illness.

Ototoxicity resulting from intracochlear perfusion of Streptococcus pneumoniae in the guinea pig is modified by cefotaxime or amoxycillin pretreatment.

Acute changes in the electrophysiology and ultrastructure of the organ of Corti were studied after microperfusion of c. 5 x 10(6) CFU of serotype 2 Streptococcus pneumoniae D39 or Escherichia coli K-12 directly into the scala tympani of guinea pigs. Hearing loss was assessed by recording the auditory nerve compound action potential response to a 10 kHz tone pip. Mean hearing loss 3 h after pneumococcal perfusion (n = 4) was 44 dB, compared to 6 dB after E. coli perfusion (n = 4) (P<0.001). After pneumococcal perfusion, scanning electron microscopy revealed damage to hair cell stereocilia and cratering of the apical surface of supporting cells. Intraperitoneal injection of 100 mg/kg cefotaxime (n = 4) or 100 mg/kg amoxycillin (n = 4) 30 min before perfusion of pneumococci significantly reduced mean hearing loss to 23 dB (P=0.01) or 20 dB (P=0.01), respectively, and diminished ultrastructural damage. The data suggest that if pneumococci invade the inner ear during meningitis, cochlear deafness may rapidly ensue.

Experimental reovirus type 3-induced murine biliary tract disease.

The aims of this experiment were: (1) to establish a reovirus type 3-induced murine model of biliary atresia/neonatal hepatitis that as far as possible corresponds to the human disease; (2) to demonstrate that the disease is histologically similar to the human disease, and to investigate the natural history of reovirus type 3 infection in this model; (3) to study the host-virus interrelationships at a molecular level; and (4) to develop sensitive assays that could be translated to the human disease. In this study we were unable to produce an exact model for extrahepatic biliary atresia (EHBA) in the laboratory mouse following a perinatal reovirus type 3 infection. However, the ability of reovirus type 3 to persist in the murine liver and the effects produced in the offspring of infected pregnant mice indicate that this preparation may provide the basis for the eventual development of the experimental model of EHBA.

Possible involvement of nitric oxide in the sensorineural hearing loss of bacterial meningitis.

Microperfusion of scala tympani with the NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP), produced marked depression of the compound action potential (CAP) and cochlear microphonic (CM) together with severe and widespread morphological damage to hair cells and supporting cells in the organ of Corti. In addition, direct perfusion of N-methyl-D-aspartate (NMDA) into scala tympani, which probably induces excess stimulation of NMDA receptors within the cochlea and which is known to lead to the release of NO, was found to elicit similar electrophysiological and structural lesions in the cochlea. Pre-perfusion of scala tympani with L-methyl arginine (L-MA), which inhibits the release of NO, or superoxide dismutase (SOD), an O2-scavenger, conferred marked protection upon the cochlea from the lesions caused by NO donors. These observations indicate that enhanced NO production is likely to be an important factor responsible for pathological insult of the cochlea. The possibility is discussed that this factor is involved in the chain of events leading to hearing loss caused by bacterial meningitis. Such hearing loss is a major sequela of bacterial meningitis in children.

Cytotoxic effects on hair cells of guinea pig cochlea produced by pneumolysin, the thiol activated toxin of Streptococcus pneumoniae.

The cytolytic toxin, pneumolysin, from the gram positive bacterium, Streptococcus pneumoniae, when perfused through the scala tympani of the guinea pig cochlea reduced the amplitude of both the compound action potential and the cochlear microphonic potential. When the surface of the organ of Corti was examined by scanning electron microscopy, both inner and outer hair cells and supporting cells were found to be damaged. Inner hair cells and outer hair cells of row 3 were the most susceptible to damage by pneumolysin, followed by row 2 and then by row 1 of the outer hair cells. Damage to hair cells included disruption and splaying of stereocilia, loss of stereocilia and complete dissolution of hair bundles. Apical surfaces of hair cells and supporting cells were torn, pitted and cratered with shrinkage and tearing of cell boundaries. Within the dose range perfused (0.05-1 micrograms/microliters in a 10 microliters aliquot), the magnitude of the physiological and anatomical lesions was concentration dependent. The cytotoxic effects of pneumolysin reported here may be clinically significant factors in deafness caused by meningitis and otitis media in humans.

Acute otitis media and otitis media with effusion in children with bacterial meningitis.

Acute otitis media and otitis media with effusion (OME) have often been observed in children with bacterial meningitis. OME has also been proposed as the mechanism of reversible hearing loss after meningitis. In this controlled study, children with acute bacterial meningitis were studied using auditory brainstem responses (ABR), otoacoustic emissions, tympanometry and otoscopy. An age- and sex-matched control was recruited for each patient and the incidence of acute otitis media and OME was compared between the two groups. One hundred and twenty-four children with meningitis were studied. Ninety-two children (74 per cent) had meningococcal meningitis. Five patients (4 per cent) had conductive hearing loss (ABR threshold > or = 30 dB HL) at the time of discharge from hospital. None of the patients or controls had acute otitis media. Patients and controls were well matched for risk factors for OME and the prevalence of middle ear effusion in patients and controls was 7.2 per cent and 11.3 per cent respectively. The relative risk of OME in the children with meningitis was 0.64 (95 per cent confidence interval 0.29 to 1.42). After nine months, three of the five children with meningitis and conductive hearing loss had regained normal hearing. In contrast to previous reports, there was no relationship between bacterial meningitis and acute otitis media or OME in this study. Nevertheless, coincidental conductive hearing defects were identified as the cause of reversible hearing loss in three patients.

Epidemiology of neonatal infections.

Neonatal infections can be considered in three groups, those acquired antenatally, perinatally and nosocomially. For many years it has been recognized that antenatal infections may cause death or serious fetal damage, but only recently have the more subtle features of antenatal infection been recognized. These include particularly the ability of some (such as toxoplasmosis) to produce disease many years later. Perinatal infection is often the result of maternal carriage of organisms, usually asymptomatically, and a variety of treatment approaches including immunotherapy (for hepatitis B) and antibacterial prophylaxis (for chlamydia) are being used to reduce the short- and long-term morbidity associated with this route of neonatal infection. Nosocomial infection in the neonatal nursery, and particularly in the neonatal intensive care unit may again lead to longer term problems in the infant, and organisms such as staphylococci or salmonella acquired during neonatal life may cause invasive disease weeks or even months later. The prevention of nosocomial infection will depend on the synthesis of a variety of approaches to reduce the number and spread of organisms in the environment of the vulnerable neonate.

Hepatitis B vaccine in the prevention of perinatally transmitted hepatitis B virus infections: initial report of a study in the West Midlands of England.

A study was carried out to evaluate the efficacy of hepatitis B vaccine in interrupting perinatal transmission of hepatitis B virus from carrier mothers to their babies. A four-dose schedule was used. Eight of nine babies of e antigen carrier mothers became actively immune when immunisations were started within 48 hr of birth. Effectiveness was reduced if immunisation was delayed. This report includes results from a total of 32 babies, the longest period of follow-up being 2 years. The success of this scheme is comparable to that of more intensive prophylaxis of immunoglobulin either alone or combined with vaccine and should be seriously considered for the babies of all hepatitis B carrier mothers.

Current trends in the management of bacterial meningitis.

The relevance of the host inflammatory response in the pathophysiology of bacterial meningitis is an important new concept. Modulation of this process by steroids may significantly affect the prognosis. We examine current trends in the clinical management of bacterial meningitis.

A comparison of stool fluid and stool dialysate obtained in vivo.

Stool fluid has been obtained for analysis by homogenization and high speed centrifugation of fresh stool. This fluid, from two healthy individuals with soft stools has been compared with stool dialysate obtained in vivo by retrieval of swallowed dialysis bags from their stools. Stool fluid was more acid, with a higher osmolality, an increased concentration of organic anions, sugar and ammonia, and a lower bicarbonate concentration than dialysate in vivo. It is suggested that in the individuals studied, dialysate in vivo may not be in equilibrium with the stool fluid surrounding it, and may not represent a true dialysate of faecal water.

Diagnosis of rotavirus gastroenteritis by smell.

Clinical features cannot differentiate rotavirus gastroenteritis from other types of diarrhoea. Sixty eight stool specimens were examined by nurses on an infant gastroenteritis ward. Of these, 69% were correctly classified by smell alone. The results are significant (p = 0.009) and support the suggestion that rotavirus stools have a characteristic smell.

Imported infections in east Birmingham children.

This 15-month prospective study of admissions to a children's ward found imported infections in 58 children (1.3% of admissions), aged between two months and 15 years. Most had visited the Indian subcontinent 14 (1-341) days earlier. Few had taken preventative measures. The commonest infection was malaria (n = 23).

The hepatotoxic action of allyl formate.

The hepatotoxic action of allyl formate on rat liver has been investigated. Biochemical changes can be detected in the liver cell many hours before the histological changes and it would appear that the toxin has a direct action on the liver parenchymal cell. The results suggest that allyl formate is not the toxic agent but that it is converted via allyl alcohol into acrolein. This reaction requires the presence of alcohol dehydrogenase. Histochemical studies have shown that this enzyme is localized in the periportal region of the liver lobule, and may explain why allyl formate solely produces a periportal necrosis. As glutathione and 1,4-dithiothreitol protect against the early biochemical changes produced by the poison, it is probable that acrolein alkylates proteins and nucleic acids.

Chronic hepatitis B in male and female children of HBsAg carrier mothers.

We have studied a group of children born to HBsAg+ mothers, resident in the English West Midlands; none of the children had sought medical attention for hepatitis B-related problems. Forty-two out of 48 children born to HBeAg+ mothers were HBsAg+. Among these children, the mean age of the HBeAg+ girls was significantly lower than that of the HBeAg+ boys (P = 0.05), suggesting that girls eradicate HBeAg at a younger age than boys. Among all children born to HBsAg+ mothers, liver function tests were normal except in 2 HBsAg+ boys who had elevated serum aminotransferase activities. Excluding these boys, serum alanine aminotransferase activity, while within the normal range, was significantly higher in HBeAg+ and anti-HBe+ children than in their immune (anti-HBs+) and non-infected siblings (P less than 0.01 and P less than 0.05). Waning infectivity was observed in many HBsAg+ mothers, giving rise to a typical pattern of infection within a family: older children, born to the still HBeAg+ mother, being HBeAg+ carriers, while younger siblings, born when the mother had become anti-HBe+, had no markers of infection. These younger children are vulnerable to 'horizontal' transmission.

Neonatal typhoid fever.

Three infants of Pakistani immigrant mothers developed typhoid fever in the neonatal period. All three survived, but two became chronic excretors of Salmonella typhi. The risk of an outbreak of typhoid fever in a maternity unit or special care baby unit is emphasized.