Eradication of H. influenzae in AECB: A pooled analysis of moxifloxacin phase III trials compared with macrolide agents.

Haemophilus influenzae is the most common bacterial pathogen associated with acute exacerbations of chronic bronchitis (AECB). This study determined the rate of bacterial eradication of H. influenzae during AECB treated with either macrolides or moxifloxacin. Adult AECB patients with H. influenzae were included in a pooled analysis of four double-blind, multicentre, randomised trials. Patients received either moxifloxacin (400 mg qd for 5-10 days) or macrolides (azithromycin 500 mg/250 mg qd for 5 days or clarithromycin 500 mg bid for 5-10 days). Bacterial eradication and clinical success were recorded at the test-of-cure visit (7-37 days post-therapy). Of 2555 patients in the intent-to-treat population, 910 were microbiologically valid and 292 (32%) had H. influenzae cultured at baseline. Bacterial eradication of H. influenzae was significantly higher with moxifloxacin vs. macrolide-treated patients (93.0% [133/143] vs. 73.2% [109/149], respectively, P = 0.001). Moxifloxacin also demonstrated higher eradication rates compared with azithromycin (96.8% vs. 84.6%, P = 0.019) and clarithromycin (90.1% vs. 64.2%, P = 0.001) analysed separately. Clinical success was 89.5% (128/143) for moxifloxacin vs. 85.2% (127/149) for the macrolide group (P = 0.278); similar results were found when moxifloxacin was compared individually with each macrolide. For patients with AECB due to H. influenzae, moxifloxacin provided superior bacterial eradication rates than macrolide therapy.

A community randomized controlled clinical trial of mixed carotenoids and micronutrient supplementation of patients with acquired immunodeficiency syndrome.

OBJECTIVE: This clinical trial aims to evaluate if natural mixed carotenoids supplementation can improve the health and survival of acquired immunodeficiency syndrome (AIDS) patients. DESIGN: A placebo-controlled, prospective, randomized, double-blind, multicenter clinical trial. SETTING: Community, tertiary care human immunodeficiency virus (HIV) clinics of the Canadian HIV Trials Network (CTN). PARTICIPANTS: Three hundred and thirty-one adults with advanced AIDS on conventional management were recruited during routine clinic visits. INTERVENTIONS: All participants, including 166 controls, received daily oral specially formulated multivitamins including vitamin A and trace elements; 165 treatment group participants received additional daily oral natural mixed carotenoids, equivalent to 120,000 IU (72 mg) of beta-carotene daily. Follow-up was quarterly at routine clinic visits. RESULTS: Mean (s.d.) follow-up was for 13 (6) months. Thirty-six participants died by 18 months. Serum carotene concentration <1.0 micromol/l was present in 16% participants at baseline. Despite variation in carotene content of the treatment medication, serum carotene concentrations increased significantly to twice the baseline levels to 18 months follow-up in participants who received carotenoids treatment compared with controls (P < 0.0001). Although not statistically significant, mortality was increased in participants who did not receive carotenoids treatment compared with those who did (HR time to death 1.76, 95% CI 0.89, 3.47, P = 0.11). In multivariate analysis, survival was significantly and independently improved in those with higher baseline serum carotene concentrations (P = 0.04) or higher baseline CD4 T-lymphocyte counts (P = 0.005). Adjusted mortality was also significantly and independently increased in those who did not receive carotenoids treatment compared with those who did (HR time to death 3.15, 95% CI 1.10, 8.98, P = 0.03). CONCLUSIONS: Low serum carotene concentration is common in AIDS patients and predicts death. Supplementation with micronutrients and natural mixed carotenoids may improve survival by correction of a micronutrient deficiency. Further studies are needed to corroborate findings and elucidate mechanism of action.

Central corneal thickness in normal, glaucomatous, and ocular hypertensive eyes.

OBJECTIVE: To determine the relationship between central corneal thickness (CCT) and applanation intraocular pressure (IOP) in normal, glaucomatous, and ocular hypertensive eyes. METHODS: One hundred nine subjects (184 eyes) were studied. Forty-eight patients (74 eyes) had glaucoma, 28 patients (51 eyes) had ocular hypertension, and 33 patients (59 eyes) were normal. Intraocular pressure as measured by applanation tonometry, refractive status, CCT, and axial length were measured for all subjects. RESULTS: The CCT (mean +/- SD) of eyes with ocular hypertension was significantly greater (0.606 +/- 0.041 mm) than that of glaucomatous eyes (0.554 +/- 0.022 mm) (P < .001) or of normal controls (0.561 +/- 0.026 mm) (P < .001). There was no significant difference in CCT between normal and glaucomatous eyes (P = .40). The axial length (mean +/- SD) of eyes with ocular hypertension (23.54 +/- 1.34 mm) was not different compared with glaucomatous eyes (23.93 +/- 0.96 mm) (P = .13) or normal eyes (23.62 +/- 1.21 mm) (P = .83). There was no significant difference between the axial length for glaucomatous eyes compared with normal eyes (P = .18). Those eyes with glaucoma being treated with topical dorzolamide hydrochloride had a significantly increased CCT (0.560 +/- 0.025 mm) compared with those eyes with glaucoma not being treated with dorzolamide (0.551 +/- 0.20 mm) (P = .02). CONCLUSIONS: The mean CCT is increased in eyes with ocular hypertension when compared with normal or glaucomatous eyes, which confirms the findings of other investigators. Increased CCT may give an artificially high IOP measurement by applanation tonometry. The CCT must be considered when developing a treatment approach for patients with ocular hypertension.

The validity of acid-fast smears of gastric aspirates as an indicator of pulmonary tuberculosis.

SETTING: A tuberculosis referral hospital in Canada. OBJECTIVE: To determine the validity of acid-fast (AFB) smears of gastric aspirates (GA) in the diagnosis of pulmonary tuberculosis, and to assess the prevalence of nontuberculous mycobacteria (NTM) in GA isolates from such patients. DESIGN: A retrospective case review of our experience with AFB smears (Kinyoun) and cultures of GA and sputum over a 3-year period. RESULTS: From 1994 to 1996 inclusive, 1155 GA were performed in 889 patients. Mycobacteria were cultured from 109 (9%) GA. Thirteen of these were positive on smear (sensitivity 19%). All GA that were positive on smear were culture positive for Mycobacterium tuberculosis. There were no false positive smears (specificity 100%). The sensitivity and specificity of the sputum smear were 45% and 99%, respectively. Of the 96 culture positive, smear negative GA, 54 grew M. tuberculosis and 42 grew an NTM. Of 13 patients who had sputum and GA studied coincidentally, and in whom the sputum was both smear and culture positive, the GA culture was positive in 13 and the smear was positive in eight (66%). CONCLUSION: AFB smear of GA is a relatively insensitive but highly specific indicator of pulmonary tuberculosis warranting institution of antituberculosis treatment. Gastric AFB smear positivity appears to reflect a high bacillary burden within the respiratory tract.

A comparison of dorzolamide-timolol combination versus the concomitant drugs.

PURPOSE: To compare the intraocular pressure (IOP) lowering effect of fixed combination dorzolamide 2% and timolol 0.5% therapy to that of concomitant administration of a topical beta-blocker and dorzolamide. METHODS: Seventy-four consecutive glaucoma patients were changed from a regimen including a topical beta-blocker and dorzolamide to the fixed combination dorzolamide-timolol in 1 eye, with the other eye used as the control. The average IOP readings before and 1 month after the change were compared. RESULTS: The mean baseline IOP in the entire study population was 19.4 +/- 4.2 mm Hg in the study eyes and 16.9 +/- 4.2 mm Hg in the control eyes. Four weeks after the medication change, the mean IOP was 17.3 +/- 3.9 mm Hg in the study eyes (P <.001) and 16.1 +/- 4.1 mm Hg in the control eyes (P =.02). The difference between the mean IOP change of 2.1 mm Hg in the study eyes and 0.8 mm Hg in the control eyes was found to be statistically significant (P =.01). CONCLUSION: These findings suggest that the fixed combination dorzolamide-timolol therapy achieves additional lowering of the intraocular pressure compared with the concomitant administration of a beta-blocker and dorzolamide.

Efficacy of autologous blood injection for treating overfiltering or leaking blebs after glaucoma surgery.

PURPOSE: To evaluate the efficacy of autologous blood injections for treating overfiltering or leaking blebs after glaucoma surgery. METHOD: Retrospective review of ten eyes of ten patients who received intrableb autologous blood injections for hypotonous maculopathy. RESULTS: After intrableb blood injection, average intraocular pressure increased from 4.3 mm Hg to 6.4 mm Hg, and average visual acuity improved from 20/88 to 20/77. These results, however, were not statistically significant. CONCLUSION: Our results with autologous blood injection are less favorable than those of previous reports, although further study with a larger case series is needed.

Sequential IV/PO moxifloxacin treatment of patients with severe community-acquired pneumonia.

BACKGROUND: IV/PO moxifloxacin was evaluated in the treatment of hospitalized patients with severe community-acquired pneumonia (CAP). METHODS: Data were pooled from two prospective, randomized studies. In the multinational study, patients received 7-14 days IV/PO moxifloxacin 400 mg QD or IV/ PO amoxicillin clavulanate 1200/625 mg TID +/- IV/PO clarithromycin 500 mg BID. In the North American study, patients received 7-14 days IV/PO moxifloxacin 400 mg QD, IV/ PO alatrofloxacin/trovafloxacin 200 mg QD, or IV/PO levofloxacin 500 mg QD. The primary endpoint was clinical success at the test-to-cure visit. Severe CAP was defined according to the 1993 ATS criteria. RESULTS: In the clinically valid population, clinical success rates were 88% (167/190) for moxifloxacin- and 83% (155/186) for comparator-treated patients (95% CI = -1.9%, 12.2%). Corresponding clinical success rates for the microbiologically valid population were 87% (59/68) and 84% (54/64), respectively (95% CI = 8.6%, 15.0%). A switch from IV to PO therapy was made by day 5 of therapy for 73% of moxifloxacin- vs. 60% of comparator-treated patients (P < 0.01). Clinical success rates were similar in a retrospective analysis using the revised 2001 ATS definition of severe CAP. Mortality rates were 6% (15/241) and 10% (24/238) in the moxifloxacin and comparator treatment groups, respectively. The incidence of drug-related adverse events was similar in both treatment groups. CONCLUSION: Sequential IV/PO moxifloxacin 400 mg QD is as safe and effective as other fluoroquinolones and a beta-lactam/macrolide combination for treating hospitalized patients with severe CAP.

Clinical and in situ cellular responses to Haemophilus ducreyi in the presence or absence of HIV infection.

We aimed to determine if the clinical and histological features of chancroid are altered by HIV infection. Male patients presenting to the Nairobi special treatment clinic with a clinical diagnosis of chancroid were eligible for the study. A detailed history, physical examination, swabs for Haemophilus ducreyi culture and blood for HIV serology, syphilis serology and CD4 counts were obtained from all patients. Punch biopsies from an ulcer were obtained from 10 patients and either fixed in 10% formalin or snap frozen in Optimum Cutting Temperature (OCT) medium compound at -70 degrees C. Patients were treated with erythromycin and followed for 3 weeks. Chi-square and Student's t-test were used to determine if the clinical and laboratory features of chancroid differed between HIV-seropositive and seronegative individuals. Cox regression survival analysis was used to determine if HIV infection altered cure rates of chancroid at 21 days. Immunohistochemical staining was performed using lymphocytic and macrophage markers and tissue sections were analysed by 2 pathologists in a blinded manner. Between February and November 1994, 109 HIV-seropositive and 211 HIV-seronegative individuals were enrolled in the study. HIV patients had ulcers of longer duration than HIV-seronegative patients (P=0.03). Although cure rates were similar at 3 weeks, HIV patients had lower cure rates at 1 week (23% v 54%, P=0.002). A dense interstitial and perivascular inflammatory infiltrate extending from the reticular to deep dermis was present in all biopsies. This consisted of equal amounts of CD4 and CD8 T-lymphocytes as well as macrophages. The histological and immunohistochemical picture was identical for HIV-positive and negative patients. HIV infection slows the healing rates of chancroid ulcers despite appropriate antibiotic therapy. This clinical difference cannot be attributed to an altered histopathological response to HIV infection. Additional studies are needed to elucidate the mechanisms responsible for this finding.

PIP: Chancroid is caused by infection with Hemophilus ducreyi, and is associated with an increased risk for the sexual transmission of HIV-1. The authors assessed whether the clinical and histological features of chancroid are changed by HIV infection, using 320 male patients who presented during February-November 1994 to the City of Nairobi Special Treatment Clinic with a clinical diagnosis of chancroid. 109 subjects were HIV seropositive and 211 were HIV seronegative. A detailed history, physical examination, swabs for Hemophilus ducreyi culture and blood for HIV serology, syphilis serology, and CD4 counts were obtained from all patients. Punch biopsies from an ulcer were obtained from 10 patients and either fixed in 10% formalin or snap frozen in Optimum Cutting Temperature (OCT) medium compound at -70 degrees Celsius. Patients were treated with erythromycin and followed for 3 weeks. HIV patients had ulcers of longer duration than did HIV-seronegative patients. Although cure rates were similar at 3 weeks, HIV patients had lower cure rates at 1 week (23% vs. 54%). A dense interstitial and perivascular inflammatory infiltrate extending from the reticular to deep dermis was present in all biopsies. The infiltrate consisted of equal amounts of CD4 and CD8 T-lymphocytes as well as macrophages. The histological and immunohistochemical picture was identical for HIV-positive and HIV-negative patients. Study findings therefore indicate that HIV infection slows the healing rates of chancroid ulcers despite appropriate antibiotic therapy. The clinical difference cannot be attributed to an altered histopathological response to HIV infection.

Clofazimine induced cardiotoxicity--a case report.

A 66-year-old Indian male who had been treated for recurrent erythema nodosum leprosum with 300 mg of clofazimine per day for 11 months presented to hospital with a 4 week history of severe gastrointestinal upset. Soon after admission he developed several short runs of ventricular tachycardia with a morphology suggestive of torsade de pointe. The patient had a slightly low magnesium level which was corrected within 2 days; however, his rhythm disturbance persisted for 5 days despite management with intravenous lidocaine. His gastrointestinal symptoms abated 2 weeks after clofazimine was discontinued. Subsequent investigations showed that the patient had a keratopathy and myelin-type figures in his polymorphonuclear white cells similar to that seen with the cardiotoxic drugs chloroquine and amiodarone. It is postulated that clofazimine alone or in conjunction with electrolyte disturbance was responsible for the patient's cardiac arrythmia.

An Id reaction to Mycobacterium leprae: first documented case.

We present a case of generalized sarcoidal dermatitis in a patient with tuberculoid leprosy. After careful consideration of the reactional states in leprosy and recognizing that id reactions occur in other mycobacterial infections, we concluded that the patient's eruption was likely an id reaction to his Mycobacterium leprae infection. It was most reminiscent of the tuberculids: lichenoid tuberculid and lichen scrofulosorum. However, its histomorphologic appearance was distinctive, showing elongated granulomata along with foci of incipient perineural granuloma formation, similar to the histomorphologic appearance of tuberculoid leprosy. A pathogenetic mechanism for this unique eruption is reviewed briefly.

Right-sided endocarditis due to Staphylococcus lugdunensis: First reported case.

Staphylococcus lugdunensis is a coagulase-negative organism first identified in 1988. It is often incorrectly identified as Staphylococcus aureus, and has been isolated as the etiological agent in over 20 cases of left-sided endocarditis. This report describes the first documented case of right-sided endocarditis caused by S lugdunensis. This experience suggests that S lugdunensis can infect native valves in the absence of any predisposing risk factors such as injection drug use.

Utility of gastric aspirates in screening for pulmonary tuberculosis in high risk subjects:The Manitoba experience.

BACKGROUND: Although gastric aspirates (GA) are one of the recommended screening procedures for asymptomatic individuals at high risk for developing tuberculosis (TB), little data exist on the utility of GA for this indication. OBJECTIVE: To determine the utility of GA as a screening tool in asymptomatic subjects who are at high risk for developing pulmonary TB. PATIENTS AND METHODS: The study population's clinical, radiographical and Mantoux skin test findings were correlated with a laboratory database of all patients who underwent GA in 1994. Subjects included in the study were those at high risk of developing TB, ie, immigrants placed under surveillance for TB postlanding in Canada (surveillance foreign-born), other foreign-born individuals from high prevalence countries, Status Indians and close contacts of patients with active pulmonary TB. RESULTS: Four hundred and twelve GAs were performed in 318 patients. Complete data were available in 243 patients. Canadian-born persons who were not Status Indians and foreign-born persons from nonendemic areas (n=37) were excluded. The remaining 206 patients had 261 GAs performed (1.27±0.7 per subject). This group consisted of surveillance foreign-born (n=57), other foreign-born (n=110) and Status Indians (n=39). Fifty-three (26%) were symptomatic and 153 (74%) were asymptomatic. Ninety-eight had a normal chest radiograph, and 108 had an abnormal chest radiograph. Fourteen subjects (26%) in the symptomatic group had Mycobacterium tuberculosis isolated from their GA versus one (0.65%) in the asymptomatic group (P<0.001). One subject (1%) in the normal chest radiograph group versus 14 (12%) in the abnormal chest radiograph group (P=0.005) had M tuberculosis isolated from their GA. Thirty-six subjects were both symptomatic and had abnormal chest radiographs. In this group, 12 (33%) had M tuberculosis isolated from their GA, while none of the patients who were asymptomatic and had normal chest radiographs had a positive M tuberculosis culture. There was no difference in the yield of GA between Mantoux skin test-positive and Mantoux skin test-negative groups. CONCLUSIONS: GAs have a low yield when used to screen asymptomatic high risk subjects. The results suggest that screening of asymptomatic individuals or those with normal chest radiographs may not be warranted. This will spare many asymptomatic subjects the discomfort of undergoing the procedure and produce a significant cost saving.

Comparison of salivary and serum enzyme immunoassays for the diagnosis of Helicobacter pylori infection.

Infection with Helicobacter pylori has been established as an important risk factor for the development of peptic ulcer disease, gastritis and gastric cancer. The diagnosis of H pylori infection can be established by invasive or noninvasive techniques. Two noninvasive enzyme immunoassays (EIAs) for antibody detection - HeliSal and Pylori Stat - were compared with histology. Both assays detect immunoglobulin (Ig) G directed against purified H pylori antigen. The test populations consisted of 104 consecutive patients scheduled for upper gastrointestinal endoscopy. Of these patients, 97 (93%) had symptoms compatible with peptic ulcer disease. Saliva and serum were collected simultaneously at the time of endoscopy. Salivary EIA had a sensitivity of 66%, specificity of 67%, positive predictive value of 67% and negative predictive value of 66% compared with the serum EIA, where the results were 98%, 48%, 64% and 96%, respectively. Although the salivary EIA is an appealing noninvasive test, it was not a sensitive and specific assay. The serum EIA also lacked specificity, but was highly sensitive with a good negative predictive value. Although a negative serum EIA rules out H pylori infection, a positive result must be interpreted in the clinical context and confirmed with a more specific measure.

Efficacy of moxifloxacin for treatment of penicillin-, macrolide- and multidrug-resistant Streptococcus pneumoniae in community-acquired pneumonia.

This pooled analysis of six prospective, multicentre trials aimed to determine the efficacy of moxifloxacin in community-acquired pneumonia (CAP) due to penicillin-, macrolide- and multidrug-resistant Streptococcus pneumoniae (MDRSP). At a central laboratory, isolates were identified and antimicrobial susceptibility determined (microbroth dilution). MDRSP was defined as resistance > or =3 drug classes. Patients received oral or sequential intravenous/oral 400 mg moxifloxacin once daily for 7-14 days. The primary endpoint was clinical success at test-of-cure for efficacy-valid patients with proven pretherapy S. pneumoniae infection. Of 140 S. pneumoniae isolated (112 respiratory, 28 blood), 23 (16.4%) were penicillin resistant, 26 (18.6%) macrolide resistant and 31 (22.1%) MDRSP. The moxifloxacin MIC90 was 0.25 microg/ml. Clinical cure with moxifloxacin was 95.4% (125/131) overall, and 100% (21/21) for penicillin-, 95.7% (22/23) for macrolide- and 96.4% (27/28) for multidrug-resistant strains. Moxifloxacin provided excellent clinical and bacteriological cure rates in CAP due to drug-resistant pneumococci.

Identifying cervical infection among pregnant women in Nairobi, Kenya: limitations of risk assessment and symptom-based approaches.

OBJECTIVES: To examine characteristics of pregnant women associated with cervical infection, and to evaluate the accuracy of symptom-based and risk assessment systems which have been developed for identifying cervical infection in antenatal women. METHODS: Interviews were conducted and physical examinations performed on 291 consecutive antenatal clinic attenders in nairobi, Kenya. Vaginal, cervical, urine and blood specimens were also obtained for analysis. RESULTS: The following disease prevalences were observed: candidiasis 26.2%; trichomoniasis 19.9%; bacterial vaginosis 20.6%; any vaginal infection 53.8%; chlamydial cervicitis (CT) 8.8%; gonococcal cervicitis (GC) 2.4%; any cervical infection 10.8%. The only statistically significant association with GC and/or CT cervical infection was the presence of cervical friability (OR = 2.1, P = 0.05). There were trends towards associations with the presence of endocervical mucopus (OR = 2.6, P = 0.06), reporting a new sex partner in the past 3 months (OR = 2.2, P = 0.16) and reporting that a sex partner had an STD-related symptom (OR = 4.4, P = 0.13). There were no associations with other demographic, behavioural or medical characteristics. Risk scores previously developed for detecting GC/CT cervicitis in developing country antenatal populations generally performed poorly. CONCLUSIONS: The prevalences of vaginal and cervical infection observed were extremely high among these "low risk" women. Owing probably to high levels of vaginal infection and to behavioural characteristics of this urban population, factors which elsewhere have been associated with cervical infection were not found to be so in this setting. Further work on symptom-based approaches and risk assessment for STD case detection in pregnant women is required before STD management recommendations can be generalised.

AIDS dementia complex with generalized myoclonus.

Focal and segmental, but not generalized, myoclonus have been described with human immunodeficiency virus (HIV) infection. We describe three patients with generalized myoclonus and acquired immunodeficiency syndrome (AIDS) dementia complex. In each, myoclonus persisted until death, invariably after a course of a few months. In two patients, myoclonus was elicited by sudden auditory stimuli and resembled a startle response. This form of myoclonus may be subcortical in origin. We suggest that the AIDS dementia complex be included among the causes of myoclonic dementia.

A case of necrotizing fasciitis due to Streptococcus pneumoniae.

We report a patient suffering from necrotizing fasciitis. The principal pathogen was Streptococcus pneumoniae. As far as we are aware, this is the first reported case of necrotizing fasciitis (NF) attributable to this organism. We discuss the pathogenesis of NF, and review the literature relating to this disorder.

Clinical significance of nontuberculous mycobacteria isolates in a Canadian tertiary care center.

To determine the epidemiology and clinical features of disease due to nontuberculous mycobacteria (NTM) in our institution, we reviewed the medical records of all patients from whom NTM isolates were recovered from 1988 to 1990 to extract selected clinical and laboratory data. On the basis of the likelihood of infection, patients were classified as having definite, probable, or unlikely NTM disease as defined by published guidelines. Of 80 patients who met the inclusion criteria, 17 had definite NTM disease, and 23 had probable NTM disease. No differences in age, sex, presence of underlying pulmonary or nonpulmonary disease, or chest radiographic abnormalities were noted between patients with and without NTM disease. More than 85% of all definite or probable cases were caused by Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium fortuitum complex. The diagnosis of NTM disease was often delayed or missed, which resulted in unsatisfactory management of patients. There is a need to educate physicians about the diagnosis and management of NTM infections.

Efficacy and safety of sequential moxifloxacin for treatment of community-acquired pneumonia associated with atypical pathogens.

In two prospective, randomized studies intravenous (IV)/oral (PO) moxifloxacin (400 mg q.i.d.) was compared to IV/PO antimicrobial comparator agents for the treatment of hospitalized patients with community-acquired pneumonia. Reported here are the pooled data for the sub-population with atypical pathogens. Of 101 intent-to-treat patients with atypical pathogens, a total of 39 moxifloxacin-treated and 47 comparator-treated subjects were microbiologically valid and included in the analysis. Clinical and bacteriological success rates were 95% for the moxifloxacin-treated and 94% for the comparator-treated subjects at the test-of-cure visit. The results indicate IV/PO moxifloxacin (400 mg q.i.d.) is an effective monotherapy for patients with CAP due to atypical pathogens.