Nitric oxide in Tanzanian children with malaria: inverse relationship between malaria severity and nitric oxide production/nitric oxide synthase type 2 expression.

Nitric oxide (NO)-related activity has been shown to be protective against Plasmodium falciparum in vitro. It has been hypothesized, however, that excess NO production contributes to the pathogenesis of cerebral malaria. The purpose of this study was to compare markers of NO production [urinary and plasma nitrate + nitrite (NOx)], leukocyte-inducible nitric oxide synthase type 2 (NOS2), and plasma TNF-alpha and IL-10 levels with disease severity in 191 Tanzanian children with and without malaria. Urine NOx excretion and plasma NOx levels (corrected for renal impairment) were inversely related to disease severity, with levels highest in subclinical infection and lowest in fatal cerebral malaria. Results could not be explained by differences in dietary nitrate ingestion among the groups. Plasma levels of IL-10, a cytokine known to suppress NO synthesis, increased with disease severity. Leukocyte NOS2 antigen was detectable in all control children tested and in all those with subclinical infection, but was undetectable in all but one subject with cerebral malaria. This suppression of NO synthesis in cerebral malaria may contribute to pathogenesis. In contrast, high fasting NOx levels and leukocyte NOS2 in healthy controls and asymptomatic infection suggest that increased NO synthesis might protect against clinical disease. NO appears to have a protective rather than pathological role in African children with malaria.

Single and multiple pyogenic liver abscesses. Natural history, diagnosis and treatment, with emphasis on percutaneous drainage.

The presenting features, modes of treatment and clinical course were reviewed for 55 patients with pyogenic liver abscess, seen at Duke University Medical Center over a 15-year period. Thirty-three patients had a solitary abscess and 22 had multiple abscesses. Most patients were between the ages of 40 and 60 years. Males predominated, 2.4:1. Major underlying conditions included biliary tract disease, malignancy and colonic disease. Eight patients, each with a solitary abscess, had no identifiable underlying condition. Symptoms and signs were nonspecific: fever, chills, focal abdominal tenderness and hepatomegaly were common. A raised serum alkaline phosphatase level was the most consistent abnormal laboratory finding. CT with contrast enhancement, radioisotope scanning and ultrasonography all accurately defined solitary hepatic abscesses. However, CT scan was more successful than other imaging techniques in detecting multiple abscesses. In seven patients the diagnosis was made only at laparotomy. Overall, a diagnosis of liver abscess was made in 50 living patients (91%). Microorganisms were recovered from pus and/or blood cultures of 44 patients (80%). Most common were enteric gram-negative facultative rods, anaerobic gram-negative rods, and microaerophilic streptococci. Single abscesses were more likely than multiple abscesses to contain more than one organism. All patients received antibiotics; the choice of antibiotic does not appear to be critical provided the regimen has a broad spectrum including activity against anaerobes. Surgical or percutaneous drainage was successful when attempted in all patients with a single abscess, but the outcome was less favorable in those with multiple abscesses. Percutaneous drainage is currently replacing open operative drainage as the method of choice. Overall mortality in patients with single abscesses was 15% (5/33) and in those with multiple abscesses 41% (9/22).

Computed tomographic evaluation of an experimental model for pyogenic liver abscesses.

Computed tomography (CT) was used to evaluate 15 rabbits with experimentally induced liver abscesses. The animals were examined both before and after intravenous contrast injection. After sacrificing the animals, postfreeze CT scans were made to mark the abdomen for 1-cm thick whole body sections for correlating the gross pathology with the results of the CT scans. CT detected 15 abscesses in 13 of the 14 rabbits with true positive lesions. Ten abscesses less than 1.4 cm in diameter were not detected by CT. Contrast agent enhancement was helpful in 70% of the studies. These abscesses have characteristics similar to human liver abscesses, but there was more gas and calcium in the experimentally induced abscesses than is encountered in humans with hepatic abscesses. The model and its CT characteristics appear well suited for future studies in the diagnosis and treatment of liver abscesses.

Seroepidemiology of Rickettsia typhi, spotted fever group rickettsiae, and Coxiella burnetti infection in pregnant women from urban Tanzania.

Immunofluorescent antibody (IFA) testing was performed on sera drawn from 150 pregnant women in the port city of Dar es Salaam, Tanzania. Prevalence of antibodies to Rickettsia typhi was 28%, higher than in any of the 12 other African countries in which serosurveys using IFA testing have been performed. Seroprevalence of antibodies to spotted fever group rickettsiae antigens was 25.3%, comparable with that found in other sub-Saharan countries endemic for Amblyomma ticks. Only 4.7% of women were seropositive for Coxiella burnetii.

An experimental model for pyogenic liver abscess.

We have developed a reproducible small-animal model for pyogenic liver abscess, suitable for investigating diagnostic and therapeutic modalities. Male New Zealand white rabbits weighing 2-3 kg were anaesthetized and the liver exposed. Gentle pressure was applied with forceps to the right hepatic lobe. A suspension of 10(5) colony forming units (cfu) Escherichia coli plus Fusobacterium necrophorum (10(6) cfu) plus Bacteroides fragilis (10(6) cfu) was immediately injected into a mesenteric vein. Two weeks later a palpable mass (mean diameter 4 cm) had developed. Thick pus could be aspirated percutaneously. Necropsy revealed a single, but often multiloculated, abscess at the site of the previous trauma. Injection of E. coli alone did not produce any abscesses and B. fragilis alone only small abscesses, with low and variable frequency. Inoculation with F. necrophorum alone produced large abscesses, and a dose-response relationship was established. This is a simple and reliable small-animal model useful in studies of imaging techniques, antibiotic regimens and invasive treatments for pyogenic liver abscess.

Impact of recent antibiotics on nasopharyngeal carriage and lower airway infection in Indigenous Australian children with non-cystic fibrosis bronchiectasis.

Indigenous Australian children have increased rates of bronchiectasis. Despite a lack of high-level evidence on effectiveness and antibiotic resistance, these children often receive long-term antibiotics. In this study, we determined the impact of recent macrolide (primarily azithromycin) and ß-lactam antibiotic use on nasopharyngeal colonisation, lower airway infection (>10(4) CFU/mL of bronchoalveolar lavage fluid culture) and antibiotic resistance in non-typeable Haemophilus influenzae (NTHi), Streptococcus pneumoniae and Moraxella catarrhalis isolates from 104 Indigenous children with radiographically confirmed bronchiectasis. Recent antibiotic use was associated with significantly reduced nasopharyngeal carriage, especially of S. pneumoniae in 39 children who received macrolides [odds ratio (OR)=0.22, 95% confidence interval (CI) 0.08-0.63] and 26 children who received ß-lactams (OR=0.07, 95% CI 0.01-0.32), but had no significant effect on lower airway infection involving any of the three pathogens. Children given macrolides were significantly more likely to carry (OR=4.58, 95% CI 1.14-21.7) and be infected by (OR=8.13, 95% CI 1.47-81.3) azithromycin-resistant S. pneumoniae. Children who received ß-lactam antibiotics may be more likely to have lower airway infection with ß-lactamase-positive ampicillin-resistant NTHi (OR=4.40, 95% CI 0.85-23.9). The risk of lower airway infection by antibiotic-resistant pathogens in children receiving antibiotics is of concern. Clinical trials to determine the overall benefit of long-term antibiotic therapy are underway.

High-resolution melting analysis of the spa locus reveals significant diversity within sequence type 93 methicillin-resistant Staphylococcus aureus from northern Australia.

High-resolution melting analysis is an inherently robust, easy and inexpensive approach to the examination of genomic regions containing single-nucleotide polymorphisms and hypervariable loci. Staphylococcus aureus sequence type (ST) 93 is a singleton, Panton-Valentine leukocidin-positive clone unique to Australia. A high-resolution melting-based method for the identification of ST93 was developed, and a similar approach was used to reveal diversity within the spa locus of this lineage. Statistical and graphical methods that account for instrumental and operator-dependent variation in high-resolution melting curves were developed, to allow greater confidence and reproducibility in deciding whether another curve is truly different from the baseline curve of an amplicon with known sequence. The data support a very early acquisition, or multiple independent acquisitions, of SCCmec by ST93 methicillin-susceptible S. aureus (MSSA), and the coexistence of MSSA and methicillin-resistant S. aureus versions of the same lineage within northern Australia.

The dynamic nature of group A streptococcal epidemiology in tropical communities with high rates of rheumatic heart disease.

Prospective surveillance was conducted in three remote Aboriginal communities with high rates of rheumatic heart disease in order to investigate the epidemiology of group A beta-haemolytic streptococci (GAS). At each household visit, participants were asked about sore throat. Swabs were taken from all throats and any skin sores. GAS isolates were emm sequence and pattern-typed using standard laboratory methods. There were 531 household visits; 43 different emm types and subtypes (emmST) were recovered. Four epidemiological patterns were observed. Multiple emmST were present in the population at any one time and household acquisition rates were high. Household acquisition was most commonly via 5- to 9-year-olds. Following acquisition, there was a 1 in 5 chance of secondary detection in the household. Throat detection of emmST was brief, usually <2 months. The epidemiology of GAS in these remote Aboriginal communities is a highly dynamic process characterized by emmST diversity and turnover.

Molecular typing of Streptococcus pyogenes from remote Aboriginal communities where rheumatic fever is common and pyoderma is the predominant streptococcal infection.

Aboriginal Australians in remote communities have high rates of rheumatic heart disease (RHD); yet pharyngitis is reportedly rare whilst pyoderma is common. Some strains of group A streptococci (GAS) have preference for the throat and others for the skin depending on M protein type. A study in three remote communities provided 350 GAS isolates for emm sequence typing, 244 were also emm pattern typed. There was 100% correlation between emm sequence and pattern type. Patterns D and E (non-throat tropic) made up 71% of throat and 87% of skin isolates although patterns A-C (throat tropic) were more common in the throat than the skin (RR 2.3, 95% CI 1.4-3.8) whilst the opposite was found for pattern D (RR 2.2, 95% CI 1.7-3.0). Pattern E favoured the throat (RR 1.4, 95% CI 1.1-1.8). Where environmental factors predispose to skin infection, emm pattern types D and E prevail, whatever the recovery site.

Pyogenic liver abscess: diagnosis, bacteriology and treatment.

Pyogenic liver abscess is an uncommon but potentially fatal disease. The accuracy of diagnosis made on clinical grounds can now be greatly improved with the use of modern organ-imaging techniques. The condition is often polymicrobial: Escherichia coli and other enteric gram-negative rods are major pathogens, with anaerobic gram-negative rods and Streptococcus milleri being increasingly recognised. Staphylococcal liver abscesses are less common, often arising in association with neutrophil disorders. Open surgical drainage along with antimicrobial chemotherapy has long been regarded as standard treatment, however, in many centres it is being displaced by percutaneous drainage under the guidance of computed tomography or ultrasound. Some patients have been successfully treated with antimicrobial chemotherapy alone. Once specimens have been taken for culture, empiric antimicrobial therapy should include a combination of an anti-anaerobe agent, an aminoglycoside and a beta-lactam drug such as ampicillin. Early diagnosis and treatment of this condition is essential for patient survival.

Activity of coumermycin against clinical isolates of staphylococci.

Staphylococci, particularly methicillin-resistant strains of Staphylococcus aureus, are major nosocomial pathogens in large hospitals in eastern Australia. At present vancomycin is the drug of choice for the treatment of life-threatening methicillin-resistant S. aureus infections. A possible alternative drug is coumermycin, a bis-hydroxy coumarin which inhibits DNA gyrase. Coumermycin activity was determined against clinical isolates from the Royal Melbourne Hospital. MICs of 639 staphylococcal isolates were determined by agar dilution. MICs and MBCs of 100 staphylococcal isolates were also determined by microdilution methods. The results showed that coumermycin was bactericidal, with MBCs of less than or equal to 4 micrograms/ml against all isolates tested. The results indicate that coumermycin is a potential alternative to vancomycin in the treatment of severe staphylococcal infections.

Strikebound: a dispute involving hospital linen.

On September 6, 1984, industrial bans were placed on the movement of linen within The Royal Melbourne Hospital. Initially, linen was stored in ward areas and, later, on hospital balconies. The dispute was not settled for 14 days; by this time, 25 beds and the Emergency Department had been closed. Stockpiled "soiled" and "infectious" linen bags posed a major safety risk. Once the bans were lifted, linen was removed and laundered under supervision, according to a carefully planned programme, in order to minimize the exposure of patients and staff members to potential cross-infection. Recommendations are made to cover infection control aspects associated with industrial disputes of this nature.

Antibiotic-associated colitis caused by Clostridium difficile: relapse and risk factors.

Relapse is a common sequel of antibiotic-associated colitis due to Clostridium difficile. It has been suggested that Cl. difficile may persist in the stools in spite of the resolution of symptoms after treatment and this may cause the relapse. Our study was designed to define the factors that predispose to relapse and to determine if prolonging treatment to clear Cl. difficile from the stools might prevent relapse. Of 60 consecutive patients, 36 with more severe disease required treatment. Treatment with either vancomycin or bacitracin was continued until the results of the examination of stools for cytotoxin became negative and Cl. difficile could no longer be cultured (sensitivity of culture was 10-100 organisms/mL). This was achieved in 35 patients who were then followed for one month. Symptoms reappeared in 10 (28.6%) of the treated patients while Cl. difficile reappeared in the stools of an additional seven patients (20%) without the recurrence of diarrhoea. On comparing those who relapsed with those who did not, the age (67.3 +/- 5.5 years in those who relapsed compared with 51.6 +/- 4.4 years; P less than 0.025, means +/- SE) and a history of recent abdominal surgery (59% of those who relapsed compared with 17%; P less than 0.05) were significantly different. Although those who relapsed had received therapy with multiple antibiotic agents more often, this was not statistically significant. Disease was not more severe in patients who relapsed, nor was it more difficult to clear the pathogen from these patients. The 24 untreated patients did not suffer symptomatic relapse. Continuation of treatment until Cl. difficile apparently is absent from the stools is expensive and does not prevent relapse. Elderly patients and those who have recently undergone abdominal surgery are more likely to suffer a relapse.

Experimental anaerobic liver abscess: observations on treatment.

Various treatment modalities for solitary anaerobic liver abscesses were evaluated in a recently-described rabbit model. In the first phase of the experiment, 35 rabbits with liver abscesses induced with Bacteroides fragilis and Fusobacterium necrophorum were randomized into four groups: surgical drainage alone, drainage plus clindamycin 150 mg IM 8-hourly, clindamycin alone, and untreated controls. Serum clindamycin concentrations in rabbits were similar to those achieved in humans. The survival of rabbits receiving antibiotic chemotherapy alone was significantly better than controls, whereas the survival of those having surgical drainage with or without chemotherapy was not. However, successful surgical drainage was followed by weight gain in surviving rabbits. In the second phase of the experiment 18 rabbits with abscesses were randomized into the same groups. Aspirates of pus from all rabbits receiving clindamycin were sterile by day 7 of treatment, but high bacterial counts were still present in the abscess cavities of control rabbits and of those undergoing drainage alone. These findings illustrate the application of a new model for pyogenic liver abscess in laboratory investigation. Their relevance to management of human pyogenic liver abscesses remains to be assessed.

Streptococcal septic vasculitis.

A case of invasive streptococcal disease is presented. Bacteraemic spread from a peritonsillar abscess produced acral purpuric plaques that blistered and ulcerated. Histology showed a vasculitic picture. Group A beta-haemolytic Streptococcus was cultured from the skin biopsy and seen on Gram stain.

Spotted fever in East Gippsland, Victoria: a previously unrecognised focus of rickettsial infection.

A new focus of spotted fever group rickettsial infection has been recognised in East Gippsland, Victoria. Seven cases have been identified among Melbourne residents after they holidayed in the area. The infections were confirmed serologically. The precise identity of the Rickettsia has not been determined.

Herpes simplex virus from the lower respiratory tract in adult respiratory distress syndrome.

Herpes simplex virus (HSV) was found in the tracheobronchial secretions of 14 of 46 (30%) consecutive patients with the adult respiratory distress syndrome (ARDS). The HSV has not hitherto been associated with ARDS, and most previous reports of HSV in the lower respiratory tract have come from autopsy material. In the present study, the diagnosis during life was initially made by identification of the characteristic inclusion bodies of HSV in bronchial epithelial cells obtained from tracheobronchial aspiration. The presence of HSV in the lower respiratory tract was associated with the need for more prolonged respiratory support and an increased late mortality.

Antibiotic-associated colitis due to Clostridium difficile: double-blind comparison of vancomycin with bacitracin.

A randomized double-blind study was carried out in patients with unresolving antibiotic-associated colitis due to Clostridium difficile, to compare the effect of bacitracin (80,000 U/day) with vancomycin (500 mg/day) on the resolution of symptoms, clearance of organism, and prevention of relapse. Forty-two patients with colitis, 9 of whom had a pseudomembrane, were randomized, 21 patients to each treatment group. The two groups were comparable in age, disease severity, and antibiotic exposure. For a 50% reduction in stool frequency the mean times (+/- SE) were 4.1 +/- 0.4 days for bacitracin and 4.2 +/- 0.4 days for vancomycin. Sixteen patients (76%) had symptom resolution after 7 days of treatment with bacitracin, compared with 18 patients (86%) given vancomycin. Patients who failed to respond were crossed over (blind) to the alternative antibiotic, but tended to be refractory to the alternative medication as well. Vancomycin-treated patients had negative toxin (83% vs. 53%, p = 0.04) and negative stool cultures (81% vs. 52%, p = 0.02) more frequently than did those patients given bacitracin. Similar numbers of patients in each group had symptomatic relapse during 1 mo of follow-up, but most of them relapsed yet again after blinded crossover therapy. Although bacitracin was significantly less effective than vancomycin in clearing C. difficile from the stools, both were of similar value in the control of symptoms in a group of patients with predominantly nonpseudomembranous colitis. In view of its low cost, bacitracin is a reasonable first-line alternative to vancomycin in the treatment of antibiotic-associated colitis.