Enteral feeding in duct-dependent congenital heart disease.

BACKGROUND: Infants with duct-dependent congenital heart lesions are treated with a prostaglandin E1 infusion. We aimed to describe the feeding strategies used at our institution in such infants, and to describe the incidence of necrotising enterocolitis (NEC) in this patient group, investigating whether enteral feeding is associated with a higher risk. METHODS: Patients diagnosed with hypoplastic left heart syndrome, coarctation of the aorta, pulmonary atresia, or transposition of the great arteries born over a defined period were identified. Premature infants, those with pre-existing gastrointestinal disease, and those who never received prostaglandin were excluded. Data were compared using univariable and multivariable logistic regression models. RESULTS: A total of 177 patients were identified, of them 18 received a diagnosis of suspected or confirmed NEC. There was no association between the diagnosis of NEC and enteral feeding (P = 0.9). CONCLUSIONS: Based on these data, there does not appear to be an association between enteral feeding and NEC in infants receiving prostaglandin.

Early determinants of atherosclerosis in paediatric systemic lupus erythematosus.

OBJECTIVES: To assess traditional and non-traditional cardiovascular risk factors and to determine the prevalence and correlates of early vascular markers of atherosclerosis in paediatric systemic lupus erythematosus (pSLE). METHODS: Fifty-four adolescents with pSLE had cardiovascular risk factor assessment, disease activity and vascular testing including carotid intima-media thickness (CIMT), flow-mediated dilatation (FMD), arterial stiffness measures, and myocardial perfusion studies. RESULTS: The traditional risk factors of hypertension, elevated triglycerides, apolipoprotein B, haemoglobin A1c and insulin levels and non-traditional risk factors of elevated homocysteine and fibrinogen were present (all p<0.001). Some arterial stiffness measures, central pulse wave velocity and characteristic impedance were elevated (p<0.001), but CIMT, FMD and myocardial perfusion were normal. Cumulative prednisone dose correlated with total cholesterol (r=0.5790, p<0.001) and elevated LDL-C (r=0.4488, p=0.0012). Hydroxychloroquine treatment correlated negatively with total cholesterol (r=-0.4867, p=0.0002), LDL-C (r=-0.4805, p=0.0002) and apolipoprotein B (r=-0.4443, p=0.0011). In multivariate analysis LDL-C correlated with cumulative prednisone dose and negatively with hydroxychloroquine treatment (R2=0.40, p<0.001). CONCLUSIONS: An increased burden of traditional and non-traditional risk factors and early evidence of insulin resistance and increased central arterial stiffness were present in paediatric SLE. Disease-specific and therapy-related factors are likely modifying these cardiovascular risk profiles warranting prospective longitudinal studies.

Systemic haemodynamics in infants with vein of Galen malformation: assessment and basis for therapy.

Systemic haemodynamics in three infants with severe cardiac failure secondary to vein of Galen malformation (VGAM) were studied using two-dimensional and Doppler echocardiography. In all cases, ventricular outputs were over two times normal and superior vena caval flows up to 10 times normal reflecting high flow through the low-resistance fistula. Severe pulmonary hypertension, right heart dilatation and retrograde flow in the descending aorta were uniformly present. Systemic blood flow below the head and neck was reduced resulting in metabolic acidosis at presentation. Two infants had patent arterial ducts, in which flow was entirely right to left and on entering the aorta passed predominantly retrogradely towards the VGAM. These findings provide a basis for understanding the pathophysiology of cardiac failure in VGAM and support treatment with pulmonary and systemic vasodilating agents.

Remote ischaemic preconditioning protects against cardiopulmonary bypass-induced tissue injury: a preclinical study.

OBJECTIVES: To test the hypothesis that remote ischaemic preconditioning (rIPC) reduces injury after cardiopulmonary bypass (CPB). DESIGN: Randomised study with an experimental model of CPB (3 h CPB with 2 h of cardioplegic arrest). Twelve 15 kg pigs were randomly assigned to control or rIPC before CPB and followed up for 6 h. INTERVENTION: rIPC was induced by four 5 min cycles of lower limb ischaemia before CPB. MAIN OUTCOME MEASURES: Troponin I, glial protein S-100B, lactate concentrations, load-independent indices (conductance catheter) of systolic and diastolic function, and pulmonary resistance and compliance were measured before and for 6 h after CPB. RESULTS: Troponin I increased after CPB in both groups but during reperfusion the rIPC group had lower concentrations than controls (mean area under the curve -57.3 (SEM 7.3) v 89.0 (11.6) ng.h/ml, p = 0.02). Lactate increased after CPB in both groups but during reperfusion the control group had significantly more prolonged hyperlactataemia (p = 0.04). S-100B did not differ between groups. Indices of ventricular function did not differ. There was a tendency to improved lung compliance (p = 0.07), and pulmonary resistance changed less in the rIPC than in the control group during reperfusion (p = 0.02). Subsequently, peak inspiratory pressure was lower (p = 0.001). CONCLUSION: rIPC significantly attenuated clinically relevant markers of myocardial and pulmonary injury after CPB. Transient limb ischaemia as an rIPC stimulus has potentially important clinical applications.

Non-invasive assessment of ventricular force-frequency relations in the univentricular circulation by tissue Doppler echocardiography: a novel method of assessing myocardial performance in congenital heart disease.

OBJECTIVE: To describe the first clinical application of a novel tissue Doppler derived index of contractility, isovolumic acceleration (IVA), in the assessment of the ventricular myocardial force-frequency relation (FFR) in the univentricular heart (UVH). DESIGN: Prospective study. SETTING: Tertiary referral centre. INTERVENTIONS: Non-invasive assessment of the myocardial FFR by tissue Doppler echocardiography during atrial pacing. RESULTS: IVA was used to measure the FFR of the systemic ventricle in patients with structurally normal hearts and in patients with UVHs. Basal IVA of the normal hearts (mean (SD) 1.9 (0.3) m/s2) was significantly greater than that of UVHs in patients with a dominant right ventricle (RV) (1.0 (0.3) m/s2) or left ventricle (LV) (0.8 (0.7) m/s2; p < 0.05 for both). Neither the absolute nor percentage change from basal to peak values of IVA with pacing differed between the three groups. Peak force developed by the normal LV was significantly greater than that of the UVH, dominant LV group but not different from that of the UVH, dominant RV group. CONCLUSION: Contractility at basal heart rate is depressed in patients with UVH compared with the normal LV. Analysis of ventricular FFRs exposes further differences in myocardial contractility. There is no evidence that contractile function of the dominant RV is inferior to that of the dominant LV over a physiological range of heart rates.

Long term somatic growth after repair of tetralogy of Fallot: evidence for restoration of genetic growth potential.

OBJECTIVE: To compare actual with predicted long term growth after early repair of tetralogy of Fallot (TOF). DESIGN: Serial preoperative and postoperative anthropometric data were converted with z scores. The presence of restrictive physiology was assessed by echocardiography. PATIENTS: 45 otherwise healthy patients who underwent repair at median age 1.6 years (range 0.2-4.9) were studied. Predicted height was determined from mid-parental height corrected for sex. RESULTS: Mean (SD) weight and height z scores at the time of surgery were significantly depressed (-1.04 (0.82) and -0.93 (0.95), respectively; p < 0.0001 for both). At latest follow up at a median age of 14.2 years (range 11-20.5), mean weight and height z scores were 0.16 (1.1) and -0.05 (0.81) (p = 0.32 and p = 0.41, respectively). The improvement between surgical and late weight and height z scores was significant (p < 0.0001 for each comparison). Catch up growth was largely complete within two years. Age at correction, duration of follow up, and prior surgical procedures were unrelated to growth. Mean current height z scores were similar to those predicted by mid-parental height. Patients with restrictive right ventricular physiology (n = 24) had a significantly greater late z score for weight (0.49 v -0.34; p = 0.01), with a similar trend for height. Low birth weight patients experienced comparable catch up growth but remained shorter than patients with normal birth weight (mean height z score -0.64 v 0.06; p = 0.03). CONCLUSIONS: Early repair of TOF results in significant acceleration of weight and height, with normalisation of long term growth and fulfilment of genetic growth potential.

Autologous stem cell transplantation for nasal NK/T-cell lymphoma: a progress report on its value.

Nasal NK/T-cell lymphoma is an Epstein-Barr virus-related, highly aggressive but localized disease in Orientals. The median survival is <1 year. Here, we update our experience on 18 patients treated with autologous stem cell transplantation (ASCT). Two patients died of mucositis and septicemia during ASCT. Relapse occurred in nine cases, including six local relapses. Compared with patients treated in remission, all patients treated in active or disseminated disease died of early relapse. Within this cohort, there was no significant survival difference between patients treated in first (CR1, n = 7) or second (CR2, n = 5) complete remissions. However, among consecutive cases analyzed, the patients receiving ASCT at CR1 showed a trend towards better overall survival compared with historical matched controls (P = 0.064). Disease relapse beyond 6 months was not seen after ASCT. Our retrospective data suggest that ASCT in CR1 is a viable consolidation therapy for local-stage NK/T lymphoma, but a randomized trial is needed to prove any definite survival benefit. For patients with relapsed, refractory or extranasal disease, early consideration for allogeneic transplantation and alternative therapy may be warranted.

T wave alternans threshold in normal children.

INTRODUCTION: Sustained microvolt-level T wave alternans (TWA) during exercise is a predictor of ventricular arrhythmia propensity in adult populations. TWA occurs in normal adults, but it is rare at < 70% of predicted maximum heart rate. An onset heart rate < or = 110 is believed to be significant. The aim of this study was to examine the feasibility of performing the test in children and to determine the normal heart rate threshold for sustained TWA in children. METHODS AND RESULTS: Alternans was evaluated during bicycle exercise in 100 normal volunteers aged 8 to 17 years. Adequate resting data were obtained in 76 of 100 children and was negative in all. Exercise data from 16 of 100 was excluded due to excessive noise. Median maximum heart rate was 192 (range 140 to 214). Sustained alternans was absent in 75 (89%) of 84. In the nine children with sustained alternans, median onset heart rate was 138 (range 120 to 158), and 7 of 9 had an onset heart rate > or = 135. Median heart rate threshold as a percentage of predicted maximum heart rate (220 - age) was 67% (range 58% to 76%). Only 1 subject (1.2%) had an onset heart rate < 60% of predicted maximum. There was no significant difference between age, gender, endurance, maximum heart rate, QRS duration, QT interval, or QTc in those with and those without sustained TWA. CONCLUSION: Noninvasive assessment of TWA is feasible at > or = 8 years of age. Sustained TWA was present in 11% of normal children, but was absent at heart rates below 120 and rare (1.2%) below 60% of predicted maximum heart rate.

Bone marrow involvement by nasal NK cell lymphoma at diagnosis is uncommon.

To look for subtle evidence of marrow involvement in nasal NK cell lymphoma at diagnosis, we retrospectively studied trephine biopsy specimens from 25 consecutive patients by 2 sensitive techniques: CD56 immunohistochemistry and Epstein-Barr virus-encoded RNA in situ hybridization (EBER ISH). Only 2 patients had marrow involvement by NK cell lymphoma at diagnosis. In 3 additional patients, marrow involvement developed during or after systemic recurrence. All 5 positive cases were revealed by EBER ISH, but only 3 cases showed CD56 immunoreactivity. Among the 5 cases, only 2 were recognized by morphologic assessment. All 5 patients died, often within a short period, compared with a mortality of 50% for patients without demonstrable marrow involvement. Marrow involvement is distinctly uncommon in nasal NK cell lymphoma at diagnosis, and EBER ISH is the most sensitive technique for the demonstration of occult NK cell lymphoma. Despite the low frequency of marrow involvement in nasal NK cell lymphoma, EBER ISH is worthwhile to identify the minor subgroup of patients with a high likelihood of early death due to disease and when autologous bone marrow or peripheral blood stem cell transplantation is contemplated.

Birth weight <1501 g and respiratory health at age 14.

AIMS: To determine the respiratory health in adolescence of children of birth weight <1501 g, and to compare the results with normal birthweight controls. METHODS: Prospective cohort study of children born in the Royal Women's Hospital, Melbourne. Two cohorts of preterm children (86 consecutive survivors 500-999 g birth weight, and 124 consecutive survivors 1000-1500 g birth weight) and a control group of 60 randomly selected children >2499 g birth weight were studied. Children were assessed at 14 years of age. A paediatrician determined the clinical respiratory status. Lung function was measured according to standard guidelines. RESULTS: Of 180 preterm children seen at age 14, 42 (23%) had bronchopulmonary dysplasia (BPD) in the newborn period. Readmission to hospital for respiratory ill health was infrequent in all groups and the rates of asthma were similar (15% in the 500-999 g birth weight group, 21% in the 1000-1500 g birth weight group, 21% in controls; 19% BPD, 18% no BPD). Overall, lung function was mostly within the normal range for all cohorts; few children had lung function abnormalities in clinically significant ranges. However, the preterm children had significantly lower values for variables reflecting flow. Lung function in children of 500-999 g birth weight was similar to children of 1000-1500 g birth weight. Preterm children with BPD had significantly lower values for variables reflecting flow than children without BPD. CONCLUSIONS: The respiratory health of children of birth weight <1501 g at 14 years of age is comparable to that of term controls.

Primary non-Hodgkin's lymphoma of the nose and nasopharynx: clinical features, tumor immunophenotype, and treatment outcome in 113 patients.

PURPOSE: To study the clinical features and outcome for primary non-Hodgkin's lymphomas of the nose/nasopharynx (NNP-NHLs) according to immunophenotype. PATIENTS AND METHODS: One hundred thirteen Chinese patients with primary NNP-NHLs that belonged to the categories E, F, G, or H according to the Working Formulation (WF), with full immunophenotypic data and complete clinical follow-up data, were analyzed in this retrospective study. RESULTS: Ninety (79.6%) patients had localized (stage I or II) disease, while 23 (20.4%) had stage III or IV disease. The lymphomas in 51 (45.1%), 24 (21.3%), and 38 (33.6%) patients showed natural killer (NK)/T- (CD56-positive), T-cell, and B-cell immunophenotype, respectively. Seventy-three patients (65.8%) achieved a complete remission, of whom 34 (46.6%) subsequently relapsed. The median follow-up time for those alive was 88 months. The 5-year actuarial disease-free and overall survival rates were 34.4% and 37.9%, respectively. Multivariate analysis showed that only stage and immunophenotype were significant for survival. NK/T lymphomas were distinctive among the three immunophenotypes in the following aspects: the highest male-to-female ratio, more frequent involvement of the nasal cavity alone, higher risk of dissemination to the skin, more frequent development of hemophagocytic syndrome, and the worst prognosis (overall median survival, 12.5 months). CONCLUSION: The three immunophenotypes studied are shown to exhibit different clinical patterns. Since the NK/T phenotype carries the worst prognosis, patients who present with NNP-NHL should have their tumors analyzed for CD56 expression.

Onychomycosis in Hong Kong.

BACKGROUND: Onychomycosis in temperate countries has been studied extensively, but few data are available on its epidemiology in tropical countries. We performed a survey of patients seen in Hong Kong for the 8-year period from January 1987 to December 1994. METHODS: A retrospective study of the mycology laboratory records of patients attending the Government Dermatology Clinics was carried out. Nail samples examined included clippings, scrapings, and drillings. Microscopy was performed on all specimens. Sabouraud dextrose agar was used for culture. RESULTS: Out of a total of 2382 nail samples (1024 (43.0%) toe, 1148 (48.2%) finger, and 210 (8.8%) unspecified site) examined, 340 (14.3%) were microscopy positive; 165 (48.5%) of these were culture positive, including 160 (97%) with dermatophyte and/or yeast, and 5 (3%) with molds. Men were affected more in the < 19 and > 50 years age groups, whereas women were affected more in the 20-50 years age group. Women were affected significantly more than men with yeasts, dermatophytes occurred more during adolescence. Dermatophytes showed a high peak in late spring, although both dermatophyte and yeast cases peaked in the summer months. Dermatophytes (29.1%) occurred more commonly than yeasts (19.4%) in microscopy-positive onychomycosis cases in Hong Kong. Trichophyton rubrum was the commonest dermatophyte, and Candida spp, other than C. albicans, were the commonest yeasts. Mixed infections (5%) were uncommon. CONCLUSIONS: Dermatophytes are more important than yeasts as a cause of onychomycosis in Hong Kong. Changes in climatic conditions affect the prevalence of dermatophytes more than yeasts.

Nonnasal lymphoma expressing the natural killer cell marker CD56: a clinicopathologic study of 49 cases of an uncommon aggressive neoplasm.

Expression of the natural killer (NK) cell antigen CD56 is uncommon among lymphomas, and those that do are almost exclusively of non-B-cell lineage and show a predilection for the nasal and nasopharyngeal region. This study analyzes 49 cases of nonnasal CD56+ lymphomas, the largest series to date, to characterize the clinicopathologic spectrum of these rare neoplasms. All patients were Chinese. Four categories could be delineated. (1) Nasal-type NK/T cell lymphoma (n = 34) patients were adults 21 to 76 years of age (median, 50 years), including 25 men and 9 women. They presented with extranodal disease, usually in multiple sites. The commonest sites of involvement were skin, upper aerodigestive tract, testis, soft tissue, gastrointestinal tract, and spleen. Only 7 cases (21%) apparently had stage I disease. The neoplastic cells were often pleomorphic, with irregular nuclei and granular chromatin, and angiocentric growth was common. The characteristic immunophenotype was CD2+ CD3/Leu4- CD3epsilon+ CD56+, and 32 cases (94%) harbored Epstein-Barr virus (EBV). Follow-up information was available in 29 cases: 24 died at a median of 3.5 months; 3 were alive with relapse at 5 months to 2.5 years; and 2 were alive and well at 3 and 5 years, respectively. (2) Aggressive NK cell leukemia/lymphoma (n = 5) patients presented with hepatomegaly and blood/marrow involvement, sometimes accompanied by splenomegaly or lymphadenopathy. The neoplastic cells often had round nuclei and azurophilic granules in the pale cytoplasm. All cases exhibited an immunophenotype of CD2+ CD3/Leu4- CD56+ CD16- CD57- and all were EBV+. All of these patients died within 6 weeks. (3) In blastoid NK cell lymphoma (n = 2), the lymphoma cells resembled those of lymphoblastic or myeloid leukemia. One case studied for CD2 was negative and both cases were EBV-. One patient was alive with disease at 10 months and one was a recent case. (4) Other specific lymphoma types with CD56 expression (n = 8) included one case each of hepatosplenic gammadelta T-cell lymphoma and S100 protein+ T-cell lymphoproliferative disease and two cases each of T-chronic lymphocytic/prolymphocytic leukemia, lymphoblastic lymphoma, and true histiocytic lymphoma. All of these cases were EBV-. Six patients died at a median of 6.5 months. Nonnasal CD56+ lymphomas are heterogeneous, but all pursue a highly aggressive clinical course. The nasal-type NK/T-cell lymphoma and aggressive NK cell leukemia/lymphoma show distinctive clinicopathologic features and a very strong association with EBV. Blastoid NK cell lymphoma appears to be a different entity and shows no association with EBV.

Detection of quinolone-resistant Neisseria gonorrhoeae.

The present National Committee for Clinical Laboratory Standards (NCCLS) guideline for testing Neisseria gonorrhoeae quinolone susceptibility defines only a susceptible category for ciprofloxacin, enoxacin, lomefloxacin, and ofloxacin, while susceptible, intermediate, and resistant categories are defined for fleroxacin. To further define the criteria for detection of quinolone resistance in gonococci, by standard disk diffusion and agar dilution methodologies recommended by the NCCLS, we tested 29 strains of quinolone-resistant N. gonorrhoeae (QRNG) recently isolated from ofloxacin-treated patients who were considered clinical failures. Regression analyses were performed on these results together with those of another 20 strains showing reduced susceptibility and 13 fully susceptible strains (ofloxacin MICs of < or = 0.25 microgram/ml). With 5-micrograms ofloxacin disks, resistance in 27 (93.1%) of the QRNG strains (MICs of > 1 microgram/ml) was detected by the criterion of a zone diameter of < 22 mm, while in the remaining 2 (6.9%), the disks failed to detect resistance. A cluster of 15 highly resistant strains showed ofloxacin MICs of > 4 micrograms/ml and zone diameters of < 13 mm. When tested with 5-micrograms ciprofloxacin disks, the corresponding values for resistance and high-level resistance of these QRNG strains were < 25 mm (MICs of > 0.5 micrograms/ml) and < 15 mm (MICs of > 2 micrograms /ml), respectively. Six strains for which ofloxacin MICs were > or = 8 micrograms/ml showed no zones at all with both 5-micrograms ofloxacin and 5-micrograms ciprofloxacin disks. These QRNG strains are now firmly established in the Southeast Asia region, and it is important for clinical laboratories to recognize these clinically resistant strains and to monitor their spread.

Aggressive T/natural killer cell lymphoma presenting as testicular tumor.

BACKGROUND: Nonnasal CD56+ T/natural killer (NK) cell lymphomas with morphologic and immunogenetic features similar to those of the distinctive nasal T/NK cell lymphoma are uncommon and have been characterized only recently. They show predominantly extranodal presentation, high stage disease, a highly aggressive course, strong association with Epstein-Barr virus (EBV), and lack of T cell receptor gene rearrangement. Only one previously reported case had a testicular presentation, although the testis is not uncommonly involved during the course of disease in both nasal and nonnasal T/NK cell lymphomas. METHODS: Three patients with T/NK cell lymphoma who presented initially with a testicular mass are reported. RESULTS: The three patients underwent orchidectomy for testicular tumor. Histologically, the testes showed diffuse dense infiltration of medium-sized or large lymphoma cells. Antiocentric growth and necrosis were prominent in two cases. The lymphoma had the following immunophenotype: CD2+ CD3 epsilon+ CD56+ compatible with T/NK cell lymphoma; two lacked staining with Leu4 (CD3), and one had weak staining. With immunohistochemical preparations, it was noted that the rete testis stained consistently for CD56, and the Leydig cells and Sertoli cells showed patchy staining. The neoplastic cells harbored EBV, as demonstrated by in-situ hybridization. Additional sites of disease were detected at the time of the diagnosis in one patient (nose) or appeared soon afterwards in all three patients (skin or gastrointestinal tract). All three patients died within 5 months. CONCLUSIONS: This study confirms that testicular CD56+ T/NK cell lymphoma tends to disseminate early, pursues an aggressive course, and is strongly associated with EBV. CD56 recognizes the neural cell adhesion molecule (NCAM), which exhibits homophilic binding properties. The expression of CD56 in the normal testicular constituents can perhaps explain the tendency for T/NK cell lymphoma to localize in this organ.

Quinolone-resistant Neisseria gonorrhoeae in Hong Kong.

OBJECTIVE: To study the serologic characters and antibiotic susceptibilities of quinolone-resistant Neisseria gonorrhoeae in Hong Kong. STUDY DESIGN: Sixty-nine strains of Neisseria gonorrhoeae isolated from clinical failure cases after treatment with ofloxacin during the period January 1, 1992, to January 1, 1995, were studied. A panel of 14 monoclonal antibodies against protein I classified these strains into 21 serovars. The pattern of serovar distribution against varying minimum inhibitory concentrations of ofloxacin was compared with 143 strains isolated from a cohort of quinolone-susceptible, clinically responsive cases. Antibiotic susceptibilities tests were performed on quinolone-resistant strains to penicillin, tetracycline, ciprofloxacin, spectinomycin, and ceftriaxone. Epidemiologic information on location of contact was collected. RESULTS: Serologic characterization showed that Bop and Bpy were the dominant serovars among quinolone-resistant strains. Most IA and other IB serovars had declined in the selection process for quinolone resistance. Antibiotic susceptibility tests showed that 81.2%, 89.9%, and 78.3% of quinolone-resistant Neisseria gonorrhoeae strains were resistant to penicillin, tetracycline, and both, respectively, whereas 10 of 69 (14.5%) of such strains displayed high-level quinolone resistance (ofloxacin minimum inhibitory concentration > 8 micrograms/ml). The quinolone-resistant strains remained fully susceptible to spectinomycin and ceftriaxone. CONCLUSIONS: Quinolone-resistant strains have become firmly established in Hong Kong. Serovar determination has documented shifts in the gonococcal population during the selection process for quinolone resistance. Places that use quinolones in the treatment of sexually transmitted diseases should be alert to the emergence of high-level quinolone-resistant Neisseria gonorrhoeae.

Emergence of multiple-antibiotic-resistant Streptococcus pneumoniae in Hong Kong.

Two hundred four strains of Streptococcus pneumoniae isolated in Hong Kong from January 1993 to May 1995 were analyzed for their antibiotic susceptibilities and epidemiological patterns. The ages of the patients from whom the strains were isolated from 1 month to 93 years (median, 53 years); the male-to-female ratio was 2.8, with a predominance of males in the pediatric group. Fifty-nine (28.9%) strains showed reduced penicillin susceptibility, including 40 (19.6%) with frank penicillin resistance (MIC > 1 microgram/ml). Tetracycline resistance alone was found in 28.4% of strains. Isolates with reduced penicillin susceptibility were more common in children than adults (40 versus 23.9%, P = 0.02), and penicillin resistance rates were significantly higher in hospitalized patients than in outpatients (39.5 versus 12.5%; p < 0.001). Penicillin resistance was significantly associated with resistance to ceftriaxone, erythromycin, and tetracycline (P < 0.01) but not with ofloxacin or vancomycin (P = 0.5). Among eight different patterns of resistance to three or more antibiotics, the commonest one (14.2%) was multiple resistance to penicillin, chloramphenicol, ceftriaxone, erythromycin, and tetracycline. Emergence of multiple-antibiotic-resistant S. pneumoniae reflects changes in the pneumococcus itself and the general indiscriminate use of antibiotics in treatment of respiratory infections in Hong Kong.