Echinocandins: Their role in the management of Candida biofilms

The importance of antifungal agents and their clinical implications has received little attention in comparison to antibiotics, particularly in the health-care setting. However, apart from bacterial infections rising in hospitals, the incidences of fungal infections are growing with the development of resistance to conventional antifungal agents. Newer antifungal agents such as echinocandins (ECs) have been extensively studied over the past decade and are recognised as a superior treatment compared with prior antifungals as a first line of therapy in tertiary institutions. Caspofungin (CAS), micafungin (MICA) and anidulafungin (ANID) are the three most widely used EC antifungal agents. The treatment of biofilm-associated fungal infections affecting patients in tertiary health-care facilities has been identified as a challenge, particularly in Indian Intensive Care Unit (ICU) settings. With the rising number of critically ill patients requiring invasive devices such as central venous catheters for treatment, especially in ICUs, these devices serve as a potential source of nosocomial infections. Candida spp. colonisation is a major precursor of these infections and further complicates and prolongs treatment procedures, adding to increasing costs both for hospitals and the patient. Analysing studies involving the use of these agents can help in making critical decisions for antifungal therapy in the event of a fungal infection in the ICU. In addition, the development of resistance to antifungal agents is a crucial factor for assessing the appropriate antifungals that can be used for treatment. This review provides an overview of ANID in biofilms, along with CAS and MICA, in terms of clinical efficacy, resistance development and potency, primarily against Candida spp.

Comparative study of platelet histamine and serotonin with their corresponding plasma oxidases in asthmatics with normals.

OBJECTIVE: Asthma is well controllable but non-curable disease. Exact pathophysiology involved is unresolved till today. Role of allergic hypersensitivity reaction in asthmatic on-set is well established. Present work is an effort to elucidate some basic points of unresolved pathophysiology of asthma taking platelets as marker. MATERIAL AND METHODS: A group of 52 normal human subjects in the age group of 20-60 years were studied for platelet histamine and serotonin levels and also for their plasma metabolising enzymes diamine oxidase (DAO) and monoamine oxidase (MAO). The data was collected for 79 asthmatic patients at different stages of asthma and accordingly were studied as four different groups of seventy nine asthmatics those were on regular treatment and were comfortable with drugs and were free from symptomatic attack formed gr. I; these (79) patients were followed-up during their symptomatic phase (gr. II) and same (79) patients immediately after their recovery from symptomatic stage studied as gr. III members. All the 79 asthmatic patients fall in gr. I, II and III in a serial manner i.e. all (n = 79) in each group. A separate group of thirty seven patients with known history of asthma but were symptom free and also off drugs for last 2-4 years formed gr. IV. RESULTS: Results showed mean platelet count in asthmatics at all four stages were in the normal range but were slightly low in comparison with normals. Both the enzymatic levels (DAO and MAO) in gr. I, II and III were significantly higher than normals but were same in the case of gr. IV patients. Low levels of platelet biogenic amines were observed in asthmatics (gr. I to gr. IV) than normals. CONCLUSIONS: Thus, study parameters showed significant difference in asthmatics and normals. Findings of the study have been utilized to understand unanswered hypersensitivity shown by the asthmatics over normal individuals (non-asthmatics).

Early experience with sparfloxacin in tuberculosis.

Between December, 1996 and July, 1997, 14 patients of advanced tuberculosis with a mean history of prior treatment of 27.4 months were put on oral Sparfloxacin 200 mg daily. One case each had lumbar spine and pelvic bone disease with abscesses, one had subcostal abscess and another had subpulmonic effusion. The remaining 10 cases had moderate clinical illness with tuberculosis (meningitis (1), massive pneumonia (1)). There was an early dramatic response to the new regime, (Sparfloxacin given along with PAS, isoniazide (2), PH with R or Doxy (2), SHRZ (4), RH (1), RHZ (2), SHRE (1), and RH + Cy Eth (1)). The only side-effect complaint was nausea. The response was good (clinical 3+ or more: 11; Radiographic > 50%: 11; smear conversion: 12) in 12 cases; one case with tuberculous meningitis died seven weeks after a temporary improvement.

Effect of prazosin GITS, atenolol, nifedipine SR, and enalapril on ADP-induced platelet aggregation.

A randomized, observer-blind, parallel-group study was carried out to compare the effect of prazosin GITS, atenolol, nifedipine SR, and enalapril on platelet aggregation, measured at a time expected to coincide with trough plasma levels of these drugs. 24 patients (age-30 to 60 yrs) with uncomplicated mild to moderate hypertension who completed a placebo run-in phase successfully were recruited in this study. They were randomly allocated to one of the 4 treatments: prazosin GITS 2.5 mg OD (Group 1), atenolol 50 mg OD (Group II), nifedipine SR 20 mg BD (Group III), and enalapril 5 mg OD (Group IV). All the drugs were given for 7 days, and blood samples were collected at 0 hr on day 1 (pre-treatment) and day 8 (post-treatment). Based on the dose (incremental concentrations of ADP)--response (% maximum aggregation) curve obtained, 2.5 microM/L of ADP was used to compare % inhibition of platelet aggregation among the 4 groups. We found that prazosin GITS inhibited % maximum aggregation significantly (p = 0.02) at 2.5 microM/L of ADP. Such inhibitory effect was not seen in any of the other groups. The inhibition produced by prazosin GITS differed significantly from the action of the other 3 drugs (p < 0.05). This antiplatelet effect of prazosin GITS bears more clinical relevance in view of the fact that it was seen at a time which is expected to coincide with the trough plasma levels of prazosin.

Bioactivity of marine organisms: Part VII--Effect of seaweed extract on central nervous system.

Alcohol extracts of marine algae (Rhodophyceae, Phaeophyceae and Chlorophyceae) were screened for their effect on central nervous system. Of 69 species investigated 8 appeared biologically active, 6 being CNS stimulant and two depressant, sites and dates of collection are given.

Effect of steam inhalation on mucociliary activity in patients of chronic pulmonary disease.

Increased mucociliary activity has been observed with several modalities, including inhalation which seems to achieve faster drug delivery. In patients of chronic lung disease, the mucociliary activity is known to be impaired. The effect of steam inhalation on mucociliary transport time was studied in these patients. It was found that steam inhalation improved mucociliary activity significantly (p < 0.001) in both groups receiving either only bronchodilators, or bronchodilators as well as steroids.

Air pollution related respiratory morbidity in central and north-eastern Bombay.

A study of 4 comparable communities in central & northeastern Bombay (2 each) among randomly matched 349 subjects in 1988-9, along with ambient sulfur dioxide (SO2), Nitrogen dioxide (NO2) & suspended particulate matter (SPM) air monitoring was carried out. The levels in winter were higher particularly for SO2 in Parel (upto 584 micrograms) in Maravali; Deonar showed lower pollution. There were inter-area differences for housing, income, residential history but age-sex differences were small; these were reduced by matching. Clinical respiratory symptoms were higher in Parel & Maravali (cough 12% and 11.2%, dyspnoea 17% & 13.3% respectively). Cardiac problems are commoner in Parel (11.0%). Smoker had cough more often but not dyspnoea. Maravali had a high prevalence for headache and eye irritation (9.5%). Those using kerosene suffered more than those using gas (22.2% as compared to 9.2%) Lung functions (FVC, FEVI) were lowest in Parel for males and in Maravali for females. Expiratory flow rates were lower at Dadar and then at Maravali. Despite lower SO2 pollution, Maravali residents suffered equally as in Parel. This may be due to added effect of diesel exhausts (NO2, SPM) or other unmeasured chemicals.

Effect of induction-delivery and uterine-delivery on apgar scoring of the newborn.

Very short or prolonged induction-delivery interval (i.e. less than 5 minutes or more than 15 minutes) and uterine-delivery interval of more than 90 seconds has a definite effect on the apgar scoring of a newborn especially when general anaesthesia is administered as compared to regional anaesthesia for caesarean section.

Comparative study of amoxycillin and amoxycillin/clavulanic acid in lower respiratory infections.

A comparison of oral amoxycillin (500 mg tds) with amoxycillin/clavulanic acid (Augmentin; 750 mg tds) for 7 to 10 days was completed in 76 patients with lower respiratory infection. In another 9 patients, intravenous Augmentin alone was administered (1.2 g 8 hourly) for 3 days followed by oral doses as above for 7 days. In 50 (59%) patients the underlying chronic lung disease was bronchiectasis. Clinical improvement (1 + or more) was seen in 66% with amoxycillin, 60% with oral Augmentin and 56% with IV Augmentin. For radiographic improvement the respective figures were 47, 53 and 44 per cent. Bacteriologically, elimination was seen in 8% with amoxycillin and 45% with Augmentin (P less than 0.01), while partial success was seen in 16 and 24 per cent respectively. While for gram positive organisms, both drugs were similar in efficacy, for gram negative strains the overall success was 27% with amoxycillin and 67% with Augmentin. The main organisms isolated were Str pneumoniae (12), Klebsiella (41), Pseudomonas (21), E coli (9), Haemophilus (7) and Staph aureus (6). For bacteriologic sensitivity and consequent success, Augmentin may be superior in respiratory infections.

Effect of 3 week oxygen therapy on functional and haemodynamic parameters in chronic obstructive pulmonary disease.

Sixteen patients with advanced chronic obstructive pulmonary disease (COPD) and stable chronic respiratory failure (pO2 less than 60 mm Hg, pCO2 greater than 45 mm Hg) were given 2-3 L/min oxygen 18 hours/day for 3 weeks. These were serially assessed for changes in pO2, pCO2, ECG, chest radiographs and haemodynamics. Initially all patients were in grade IV heart failure. There was no change in lung function after oxygen treatment but right descending pulmonary artery diameter and cardiothoracic ratio decreased significantly (P less than 0.01), as also the height of the P wave in ECG (P less than 0.05). There were significant changes in mean pO2 (51.8 to 61.9 mmHg; P less than 0.01), pCO2 (55.3 to 47.6 mmHg; P less than 0.001), mean pulmonary artery pressure (41.8 to 34.5 mmHg; P less than 0.01) and pulmonary vascular resistance (PVR) (346.4 to 163.3 dynes; P less than 0.05). The initial (P less than 0.05) and 3 week (P less than 0.01) pO2 levels correlated with the right descending pulmonary artery diameter. The height of the P wave also correlated with pO2 (P less than 0.01). The changes in pO2 levels correlated with those of the PVR and pulmonary blood flow (P less than 0.05). Three week oxygen therapy resulted in objective improvement in advanced COPD cases.

Quantitative evaluation of muscle relaxation induced by Kundalini yoga with the help of EMG integrator.

The present work is aimed to quantify the degree of relaxation of muscle under the effects of Kundalini Yoga with the help of EMG integrator. The data collected from 8 individuals (4 males 4 females) on the degree of muscle relaxation at the end of meditation revealed a significantly decreased muscle activity amounting to 58% of the basal level in both the sexes.

Changes in bronchoalveolar lavage and lung function in rheumatoid arthritis. A controlled study.

A comparative study of bronchoalveolar lavage was done in 30 patients with chronic rheumatoid arthritis and 30 age matched controls. Twelve patients had clinical lung disease (group I), 11 had lavage changes (group II) and 7 showed no abnormalities (group III). In group I, there was lower lung functions, tendency to older age and slightly longer history. There were no differences between the three groups (63% positive) in RA factor positivity. In the controls, lavage showed 67.3% return, 154.5 cells/cmm, 92.8% macrophages, 5.2% lymphocytes, 1.9% polymorphs and 0.2% eosinophils. In contrast, group I patients showed more polymorphs (10.3 +/- 8.3%) and group II more lymphocytes (14.5 +/- 18.7%; P less than 0.05). Thus, in chronic rheumatoid arthritic patients, bronchoalveolar lavage abnormalities may occur alone or in association with radiographic and functional abnormalities.

Role of metronidazole in improving response and specific drug sensitivity in advanced pulmonary tuberculosis.

One hundred and thirty-seven patients of advanced pulmonary tuberculosis were randomly allocated to receive metronidazole 400mg tid (76) or placebo (61) for 2 months in a single blind study. All received streptomycin 0.75 g,INH 30 mg and rifampicin 450 mg daily as standard antitubercle treatment. There were no significant pretreatment differences, among both groups. Compared to placebo group there was superior clinical improvement in metronidazole treated group at 4 and 8 weeks (81% vs 53%-P less than 0.05; 87% vs 72%-P less than 0.05 respectively), greater sputum reduction at 4 weeks (49% vs 9%-P less than 0.001) greater radiologic improvement at 4 weeks (60% vs 43%-P less than 0.01) and a better antituberculous drug sensitivity. Metronidazole seems to have beneficial adjuvant role in the drug treatment of tuberculosis. This may improve response in advanced cases.

A study of lung function and oxygen uptake during exercises in cases undergoing mitral valve surgery.

In 1986-7, 80 cases with isolated mitral valve disease undergoing open heart surgery were studied, for spirometry, resting and exercise, oxygen uptake (VO2) preoperatively and 3 months postoperatively. Pulmonary artery pressures (PAP) were recorded prior to surgical correction and soon afterward. Pulmonary hypertension was mild (I) in 56.2%, moderate (II) in 25% and severe (III) in 18.8% cases. Though spirometric functions were lower with severe PH, these did not improve significantly 3 months later. But direct MBC improved significantly in grs. I and II, along with exercise VO2 and mean PAP. (DMBC:75.7 lit. to 91.8 lit: P less than 0.001; Exercise VO2 798 ml to 983 ml: P less than 0.001). Mean PAP 56.8 to 39.5 mm: P less than 0.001). Thus these functions may be used to objectively evaluate physiologic changes in cardiac surgical cases.

Bombay experience in intensive respiratory care over 6 years.

The experience of the intensive respiratory care in 930 cases treated from 1983 for 4 years and in 404 cases over the next 2 years is reported. The background operational problems are stressed. Those between age 10 and 50 years did significantly better (p less than 0.05). The survival over the first 4 years in IPPR cases was 16.3% and in non IPPR group 71.8%; over the next 2 years, the former group, survival was 32.4 and 36.3%. The survival in asthmatic patients was high (76%). In cases with organophosphorus poisoning (without IPPR), survival was 81% while in IPPR group it was 29%. In 1988, the results in this group were better due to more aggressive management. In autopsy data on 85 cases, infection was not a major feature in those dying within 24 hours. The survival in COPD cases showed significant relation to age (p less than 0.05), initial arterial pO2 below 60 mm (p less than 0.01) and arterial pH below 7.3 (p less than 0.01). In cases with pneumonia (also asthma) younger cases did better (p less than 0.05) as also those with pneumonia and initial pO2 above 60 mm (p less than 0.01) and pH above 7.3 (p less than 0.001). When pneumonia was community acquired, survival (64.8%) was better than when it was hospital acquired (24%; p less than 0.01). Only the need for IPPR affected survival in trauma group. The major cause of death was infection with Klebsiella, Pseudomonas, Staphylococci and other gram--ve organisms. It is concluded that with proper planning and training, the IRCU does provide a useful mode of treatment in selected patients with respiratory problems.

Value of bronchoalveolar lavage in interstitial lung diseases.

Fifty-eight patients of interstitial lung diseases and 30 control patients were submitted to bronchoalveolar lavage (BAL) with flexible fibreoptic bronchoscopy. In 30 controls (with fluid recovery 61.7%) total cell count was 175 +/- 31/mm3 with macrophages 87.5 +/- 2.0%, neutrophils 7 +/- 1.9 and lymphocytes 5 +/- 0.6%. In idiopathic interstitial fibrosis (34 cases) these values were respectively 832 +/- 221/mm3, 47 +/- 5.5, 29 +/- 5.0 and 19 +/- 5 percent (significantly different P: less than 0.005, 0.001, 0.1 and 0.005 respectively from control. The results of bilateral lavages in 28 interstitial cases were similar. In other categories viz: sarcoidosis(8), macrophages were significantly fewer (61 +/- 10%: P less than 0.05) and lymphocytes significantly more (27 +/- 6.4%: P less than 0.05); in rheumatoid lung disease (4 cases) significantly fewer macrophages (45 +/- 5) were seen and 12 cases with methyl isocyanate exposure showed insignificant changes.

Comparative study of methods of detection of hepatitis 'B' surface antigen (HBsAg).

The serum samples were collected from 52 patients of acute viral hepatitis and 235 hospital staff from Kasturba Hospital for Infectious Diseases. HBsAg was detected in their sera by counter-immuno-electrophoresis (CIEP), reverse passive hemogglutination (RPHA) and by micro-enzyme-linked-immunosorbent assay (ELISA) technique. Among the patients, HBsAg was detected in 12 cases (23%) by CIEP, in 18 cases (34%) by RPHA and in 23 patients (45%) by ELISA. In the hospital staff, HBsAg was detected in 4 samples (1.7%) by CIEP, in 8 samples (3.5%) by RPHA and in 32 samples (13.5%) by ELISA. Thus ELISA was found to be the most sensitive technique in detecting HBsAg.

Chloramphenicol resistant Salmonella species isolated between 1978 and 1987.

During the ten year study i.e. 1978 to 1987, out of 53,251 cases of suspected enteric fever, S.typhi was isolated from 4005 cases (7%) and S.para typhi 'A' from 1108 cases (2.5%). A total of 52 strains of S. typhi and 4 strains of S.para typhi 'A' were found to be resistant to chloramphenicol. Minimal inhibitory concentration was greater than 256 micrograms/ml of all the strains of S.typhi and S.para typhi 'A'.