An outbreak of multi-drug-resistant tuberculosis in a London teaching hospital.

We describe the epidemiology and control of a hospital outbreak of multi-drug-resistant tuberculosis (MDR-TB). A human immunodeficiency virus (HIV)-negative patient with drug-sensitive tuberculosis developed MDR-TB during a period of unsupervised therapy. She was admitted to an isolation room in a ward with HIV-positive patients, but the room, unbeknown to hospital staff, was at positive-pressure relative to the main ward. Seven HIV-positive contacts developed MDR-TB. The diagnosis in the second patient was delayed, partly because acid-fast bacilli in his sputum were assumed to be Mycobacterium avium-intracellulare. All the available Mycobacterium tuberculosis isolates were indistinguishable by molecular typing. Nearly 1400 staff and patient contacts were offered screening, but the screening programme detected only one of the cases. Despite therapy, the index patient and two of the contacts died. HIV-positive patients are more likely than others to develop tuberculosis after exposure, and the disease may progress more rapidly. In these patients the possibility that acid-fast bacilli may represent M. tuberculosis must always be considered. Patients with tuberculosis (suspected or proven) should not be nursed in the same wards as immunosuppressed patients, and should be isolated. MDR-TB cases must be isolated in negative-pressure rooms. Hospital side-rooms may be positive-pressure as a fire safety measure; infection control teams must be aware of the airflows in all isolation rooms, and must be consulted during the design of hospital buildings. Good communication between infection control teams and clinicians is important, and all medical and nursing staff must be aware of the principles of management of patients with proven or suspected tuberculosis and MDR-TB.

Disposition of intravenous 123iodopentamidine in man.

This study compared the disposition of the radiopharmaceutical [123I]iodopentamidine with that of pentamidine after intravenous infusion by measuring plasma concentrations of each using scintilation counting and high-performance liquid chromatography (HPLC), respectively. There was rapid hepatic uptake and biliary excretion of the 123I label. Distribution kinetics of the 123I label were similar to those of pentamidine, but its elimination half-life (41 +/- 27 h) was longer than that of pentamidine measured by HPLC (11 +/- 8 h). [123I]iodopentamidine distribution reflects that of pentamidine, but elimination of the radiopharmaceutical appears slower.

Increased resistance to acute respiratory acidosis in isolated cardiac muscle following chronic hypoxia-induced hypertrophy.

OBJECTIVES: Hypertrophied myocardium is more sensitive to ischaemic dysfunction and damage. The objective of this study was to determine the effect of respiratory acidosis on cardiac muscle function following hypoxia-induced right ventricular hypertrophy, and to ascertain the role of Na(+)-H+ antiporter, which is known to be associated with cell growth. METHODS: Wistar rats were maintained at 10% O2 for 1 or 4 weeks. Experiments were performed on right ventricular papillary muscles stimulated at 1 Hz, and developed tension was recorded. The effect of respiratory acidosis was examined by equilibrating the perfusing solution with increasing levels of CO2, and the role of the Na(+)-H+ antiporter was determined by preincubation with the inhibitor 5-(N,N-hexamethylene) amiloride (HMA). Data were analysed by comparison of the slope of the semi-log plot of normalised tension against pH. RESULTS: Right ventricular hypertrophy was apparent after both 1 and 4 weeks of hypoxia. Respiratory acidosis reduced developed force in preparations from all groups, but the relationship between log tension and pH in the 4-week hypoxia group was less steep than in controls (4-week hypoxia 0.736 (0.057); control 0.947 (0.067); P < 0.01). In the 1-week hypoxia group however the relationship was steeper (1.243 (0.090); P < 0.01). HMA increased the slope in all groups, and under these conditions the control and 4-week hypoxia groups were not significantly different (control 1.134 (0.080); 4-week hypoxic 1.083 (0.087); P > 0.05). CONCLUSIONS: The increased resistance to respiratory acidosis of hypertrophied cardiac muscle following 4 weeks of hypoxia was abolished by HMA. This implies that it is related to increased activity of the Na(+)-H+ antiporter. The mechanism underlying the decreased resistance to acidosis following 1 week of hypoxia is unclear, but is unlikely to involve the Na(+)-H+ antiporter.

Domiciliary oxygen therapy.

Domiciliary oxygen is prescribed widely and often with benefit. However, patients with chronic lung disease, in whom its efficacy is proven, continue to be denied adequate assessment and treatment. It is time to ensure that this expensive treatment is given to those who will benefit in a manner that maximizes the improvement in the quality of life.

Tine testing in HIV positive patients.

BACKGROUND: The incidence of tuberculosis is increased in HIV positive patients. Purified protein derivative (PPD, tuberculin) testing has not been performed routinely on patients infected with HIV in the UK and its usefulness in diagnosing tuberculosis in these patients is unclear. METHODS: 198 HIV positive patients were Tine tested and a CD4+ lymphocyte count and chest radiograph were performed. Of the 179 male patients 164 were homosexual or bisexual, 11 were injecting drug users (IDUs), and four were both homosexual and IDUs. Of 19 women 14 were heterosexual and five were IDUs. Patients assessed their own skin reactions at 72 hours, recording the grade on a card which was returned by post. Patients with a grade 0 reaction were requested to have a second test one month later. RESULTS: Details were available on 168 of the 198 patients. Grade 0 reactions occurred in 89 of the 168 patients, requiring a second Tine test, and 73 completed Tine 2 results were received. Of 57 patients with CD4+ lymphocyte counts below 200/mm3, low grade PPD reactivity was seen in 18 on Tine 1 and nine on Tine 2. No history of BCG immunisation of tuberculosis was found in 33 Tine positive patients. Two patients treated for tuberculosis in the previous six months were PPD positive with CD4+ counts of 60/mm3 and 4/mm3 respectively. CONCLUSIONS: PPD reactivity may be maintained despite a CD4+ count of 100/mm3 or less when there is a history of tuberculosis or BCG immunisation.

Acute oxygen therapy.

Tissues require oxygen for survival. Its delivery depends on adequate ventilation, gas exchange and distribution in the circulation. Many causes of hypoxaemia can be corrected by adding oxygen to the inspired air but response is variable and must be measured.

Lung deposition of nebulised pentamidine in children.

BACKGROUND: Nebulised pentamidine is effective for preventing Pneumocystis carinii pneumonia in adults with acquired immunodeficiency syndrome. The nebuliser dose required to produce equivalent lung concentrations of pentamidine in children is unknown. This study was performed to measure pulmonary pentamidine deposition in children and to relate this to age, ventilation pattern, and body size. METHODS: Nebulised pentamidine (50 mg in 6 ml saline) was administered to 12 children (including one with lymphocytic interstitial pneumonitis) and to six adults with human immunodeficiency virus infection using a Respirgard II nebuliser. Technetium-99m labeled colloidal human serum albumin was used as an indirect marker for pentamidine and deposition in the lungs was detected by a gamma camera. RESULTS: Absolute deposition of pentamidine was not related to age, height, weight, spirometry, or ventilation characteristics. Deposition, as a mean (SD) percentage of nebuliser output, was similar in children aged 8-11 years (5.5(2.4)%), teenagers aged 12-15 years (7.2(2.2)%) and adults (7.1(2.6)%). Aerosol concentration within the lungs (% nebuliser output deposited/predicted total lung capacity) was therefore higher in children (1.9(1.5)%/1) and teenagers (1.9(0.7)%/1) than in adults (1.0(0.7%)/1), and was negatively correlated with height (r = -0.69) and weight (r = -0.50). Deposition of aerosol in the region of the large central airways was particularly marked in children. Small reductions in forced expiratory volume in one second and forced vital capacity after treatment did not differ significantly between adults and children and visual analogue scores of subjective adverse effects did not vary with age. CONCLUSIONS: These results suggest that children probably require lower nebuliser pentamidine doses to produce lung pentamidine concentrations equivalent to those found to be effective for preventing P carinii pneumonia in adults using the Respirgard II nebuliser.

Disposition of nebulized pentamidine measured using the direct radiolabel 123I-iodopentamidine.

The pulmonary deposition of nebulized pentamidine (300 mg, Respirgard II nebulizer) was measured in seven human immunodeficiency virus (HIV)-positive men using a new radiopharmaceutical, 123I-iodopentamidine. Mean total pulmonary deposition was 15.3 mg or 5.1% of the initial nebulizer dose. Further studies in two of the patients showed that at 24 h, 87% of deposited 123I was retained in the lungs. Small amounts of activity (expressed as a percentage of the initial nebulizer activity) were also detected over the thyroid (0.4%), bladder (1%) and gut (0.7%). The ratio of 123I activity to pentamidine concentration was similar in the nebulizer solution and urine. These results suggest that 123I-pentamidine may be sufficiently stable in vivo to be used to study the biodistribution of inhaled and parenteral pentamidine in humans.

Portable liquid oxygen and exercise ability in severe respiratory disability.

BACKGROUND: The development of portable liquid oxygen systems, capable of delivering high flow rate oxygen for long periods, justifies reassessment of the value of supplemental oxygen to aid exercise tolerance in patients with chronic respiratory insufficiency. The type of exercise test and the low oxygen flow rates previously used may account for the variable and often poor responses to supplemental oxygen reported in earlier studies. METHODS: The walking tolerance of 30 patients with severe respiratory disability was measured while they were breathing air and increasing doses of supplemental oxygen (2, 4, 6 1/min) by using both the standard six minute walking test and an endurance walking test. To assess the initial learning effect and repeatability of the walking tests, three six minute walks and three endurance walks were performed on day 1 and a single walk of each type on days 2, 3, and 14. In addition, oxygen dosing studies were performed on days 2 and 3 after the initial baseline walking tests. Each dosing study comprised four endurance walking tests or four six minute walking tests with patients breathing either air at a flow rate of 4 1/min from a portable cylinder or supplemental oxygen at a flow rate of 2, 4 or 6 1/min from a portable liquid oxygen supply. The order of the tests was randomised. Walking distance with each flow rate of oxygen was compared with walking distance with patients carrying cylinder air and for the initial unburdened walks. Breathlessness was assessed by visual analogue scoring on completion of each walk. RESULTS: Exercise ability and breathlessness were significantly improved with supplemental oxygen and this benefit outweighed the reduction in performance resulting from carrying the portable device. Supplemental oxygen at flow rates of 2, 4, and 6 1/min increased mean endurance walking distances by 37.9%, 67.7% and 85.0% and six minute walking distances by 19.2%, 34.5%, and 36.3% by comparison with distances when the patient was carrying air with a flow rate of 4 1/min. The additional work of carrying the portable gas supply reduced endurance walking distance by 22.2% and six minute walking distance by 14.1% by comparison with a baseline unburdened walk. Comparison of supplemental oxygen at 2, 4, and 6 1/min with the baseline unburdened performance showed increased endurance walking distances of 7.3%, 30.4%, and 43.9% and six minute walking distances of 2.3%, 15.5%, and 17.0%. Walking distance was increased by more than 50% by comparison with an unburdened walk in seven patients with the endurance walking test but in only three patients with the six minute walking test. The benefit was similar in patients with obstructive and with interstitial lung disease. Individual responses were variable and only desaturation during the baseline walk in patients with obstructive lung disease had any predictive value for benefit with oxygen. CONCLUSION: As there was no clear relation between response to oxygen therapy and the patients' characteristics, assessment for supplemental oxygen therapy will depend on exercise testing. It is suggested that portable oxygen should be considered only if a patient shows a 50% improvement in exercise ability with high flow rate oxygen (4-6 1/min) by comparison with an unburdened walk.

Which apparatus for inhaled pentamidine? A comparison of pulmonary deposition via eight nebulisers.

Aerosolised pentamidine 300 mg in 5 or 6 ml solution was administered via 8 different nebuliser systems to 12 patients with acquired immunodeficiency syndrome. Using 99mTc human serum albumin as an indirect marker for pentamidine, pulmonary, extrapulmonary (gastric and oropharyngeal) and alveolar deposition of pentamidine were measured using a gamma camera. Side effects (visual analogue scales) and changes in lung function associated with each treatment were also quantified. Deposition was completed more rapidly with the ultrasonic than the jet nebulisers. Mean total pulmonary depositions (mg +/- SEM) were Respirgard II, 6.1 +/- 0.5; Centimist, 7.3 +/- 1.0, System 22 Mizer, 14.3 +/- 2.1; System 22 Mizer with particle separator; 4.5 +/- 0.4; System 22 Mizer with Optimist 2, 6.3 +/- 0.9; Fisoneb, 6.0 +/- 1.2; Pentasonic (Portasonic); 4.6 +/- 0.9; Samsonic, 2.9 +/- 0.4. Differences between the nebulisers for peripheral lung and alveolar deposition reflected this pattern. Side effects scores were largest with System 22 Mizer, Pentasonic (Portasonic), and Fisoneb, and these produced the greatest oropharyngeal and gastric deposition. The largest reductions in lung function were associated with System 22 Mizer. A 300 mg dose of pentamidine nebulised via Respirgard II is known to be effective prophylaxis for Pneumocystis carinii pneumonia when given once monthly. Our results show that equivalent pulmonary deposition can be produced by other nebulisers. System 22 Mizer gives over twice the deposition associated with Respirgard II, and used with a pentamidine dose of 150 mg is likely to produce an adequate lung dose for prophylaxis. This nebuliser, however, is associated with more marked side effects.

Prophylaxis and treatment of Pneumocystis carinii pneumonia.

Although Pneumocystis carinii pneumonia (PCP) can occur in any patient with severe impairment of immunity, there has been a sharp rise in incidence with the spread of human immunodeficiency virus through the USA and Western Europe, where nearly 80% of patients with HIV infection have at least one episode of PCP during their lifetime (Murray et al, 1984).