Will ceftazidime/avibactam plus aztreonam be effective for NDM and OXA-48-Like producing organisms: Lessons learnt from In vitro study

Introduction: Carbapenem resistance (CR) in Klebsiella pneumoniae is mainly mediated by bla NDM and bla OXA-48 carbapenemases. Newer Food and Drug Administration-approved antimicrobial ceftazidime/avibactam (C/A) has a potent activity against bla OXA-48-like producers. However, its activity is limited in organisms co-producing bla NDM and bla OXA-48-like. Addition of aztreonam (ATM) to C/A potentially expands the spectrum of coverage for carbapenemase co-producers. With this, we aimed to determine the synergistic activity of combination of C/A plus ATM against bla NDM, bla OXA-48-like and co-producers of bla NDM + bla OXA-48-like producing CR Klebsiella pneumoniae (CRKp). Materials and Methods: A total of 12 isolates of CRKp-harbouring genes encoding bla NDM and bla OXA-48-like were tested. Minimum inhibitory concentrations (MICs) were determined for several antimicrobial agents, including C/A (0.5�?g/ml) by broth microdilution method. Checkerboard assay was performed for the combination of C/A plus ATM at varying concentrations. Fold differences in the MIC of C/A with and without addition of ATM were determined to infer synergistic effects. Results: MIC of C/A and ATM ranged from 0.5 to >8 ?g/ml and 64 to 2048 ?g/ml, respectively. Two isolates were susceptible to C/A with MIC of 0.5 and 1 ?g/ml, while others were resistant with MIC of >8 ?g/ml. Synergistic effects of >8-fold MIC difference in C/A MIC were noted with addition of ATM at 4 ?g/ml. This was observed for all CRKp with profiles of bla NDM, bla OXA-48-like and co-producers of bla NDM + bla OXA-48-like genes, which was a promising effect. Notably, all five of the colistin-resistant CRKp were inhibited with >8-fold MIC difference in the combination of C/A plus ATM at 4 ?g/ml. Conclusion: With the increasing burden of CRKp, the use of C/A with ATM combination seems to be very promising, especially for bla NDM, bla OXA-48-like and co-producers of bla NDM + bla OXA-48like carbapenemases.

Outcomes of renal transplantation in patients with immunoglobulin A nephropathy in India.

BACKGROUND: There is a paucity of data on the course of renal transplant in patients with immunoglobulin A (IgA) nephropathy (IgAN) from India. While the natural history of IgAN in the Indian context is rapidly progressive, the post-transplant course remains speculative. AIM: To study the graft survival in renal transplant recipients whose native kidney disease was IgAN and the incidence and correlates of recurrent disease. SETTINGS AND DESIGNS: Retrospective case control study from a Nephrology unit of a large tertiary care center. MATERIALS AND METHODS: The outcomes of 56 transplant patients (58 grafts) with biopsy-proven IgAN and of 116 patients without IgAN or diabetic nephropathy, transplanted during the same period were analyzed. Correlates of biopsy-confirmed recurrent disease were determined. STATISTICAL ANALYSIS: Means were analyzed by Student's t test and Mann-Whitney test; proportions were determined by Chi-square analysis and graft survival curves were generated using the Kaplan-Meier. RESULTS: Five-year graft survival for IgA patients was not significantly different from that in the reference group (90% and 79%, P = 0.6). During a mean follow-up of 42 months (range, 1-144), 28 event graft biopsies were required in 20 grafts of IgAN. Histological recurrence was diagnosed in five of the 20 available biopsies (25%) after a mean duration of 28 months. Recurrence did not correlate with donor status, HLA B35 and A2, recipient age, gender or immunosuppression. CONCLUSIONS: Renal transplantation is an appropriate treatment modality for IgA nephropathy patients with end-stage renal disease in India, despite the potential for recurrent disease. The posttransplant course is an indolent one when compared to the malignant pretransplant phase.

Mucormycosis isolated from perilymphatic tissue: an unusual presentation.

We present a rare case of a patient who presented with atypical cranial nerve palsies, with subsequent isolation of mucormycosis from an upper neck subcutaneous swelling. This is an unusual initial site of isolation of mucormycosis. We believe that this should be considered among the differentials when a diabetic or immunosupressed patient presents with cervical lymphadenopathy and cranial nerve palsies.

Cardiovascular response in anemia.

OBJECTIVE: To study the functional consequences of nutritional anemia by evaluating the exercise performance in these children. METHODS: The study was conducted on 30 each of anemic and normal children of both sexes aged between 7 and 14 years. Relevant history was taken, and detailed examination was done. These children were classified according to severity of anemia based on hemoglobin estimation as mild (10-11.9 g/dl), moderate (7-9.9 g/dl) and normal (>12 g/dl). Children with severe anemia (Hb < 7g/dl), heart disease, non-nutritional anemia, acute febrile or respiratory illness were excluded. The subjects were tested on Mortara X Scribe colour stress treadmill using the modified Bruce protocol. Continuous computerised electrocardiographic analysis was done. The parameters studied included heart rate, systolic blood pressure, double product (DP = HRxSBP), ECG changes, metabolic equivalents (METS) and exercise duration. The end point of the test was a HR of 170/min (non-fatigue group) or inability to perform further (fatigue group). Statistical analysis was done by appropriate tests. RESULTS: Fifteen children each with mild and moderate anemia and 30 age-matched controls were enrolled in the study. There was no significant difference in the resting HR, exercise duration or DP between the cases and controls. Thirty-one children reached the target HR (non-fatigue group). The end-point HR was significantly lesser among the anemic children in the fatigue group (P 0.04). The percent gain of SBP, at peak exercise (P 0.0007) and recovery SBP as percent of resting SBP (p 0.006) were significantly more in the anemic children, more so in the mildly anemic ones. Lesser METS was achieved by anemics as compared to controls (P 0.04). ECG changes occurred significantly more often in anemic children, 53.8% of those with changes being moderately anemic, the main abnormality being ST depression. None developed arrhythmia during exercise testing. CONCLUSION: The cardiovascular response to physical exercise is compromised in children with nutritional anemia and hence these children may never attain their full potential in various school activities. Prevention of anemia should be a priority in school going children.

Sensorineural hearing loss following acute bacterial meningitis in non-neonates.

OBJECTIVE: Sensorineural hearing loss (SNHL) is an important sequelae of acute bacterial meningitis (ABM) in children. This study was undertaken to determine the incidence of SNHL following meningitis in non-neonates and its correlation with various factors. METHODS: Children between the ages of 1 month and 12 years with ABM admitted in a teaching hospital over a period of 18 months were enrolled. Detailed history was taken, clinical examination performed and cerebrospinal fluid analyzed at commencement of therapy, 48 hours later and at the end of treatment. On discharge brainstem evoked response audiometry (BERA) was recorded. Data were analyzed using appropriate statistical tests. RESULTS: Out of 32 children enrolled, 9 (28.1%) developed SNHL, bilateral in 21.9% and unilateral in 6.2%. Among hearing impaired subjects, 11.2% had mild while 44.4% each had moderate and profound hearing loss. Age, presence of vomiting, altered sensorium seizures and aminoglycoside usage were not significantly different in those with and without SNHL, but the total duration of fever was (p<0.05). There was significantly higher protein content and neutrophils in the second CSF sample of those with SNHL. CONCLUSION: There is a greater than 50% probability of the child developing SNHL if neutrophil percentage in the second CSF is 80% or more. Since the overall risk of SNHL is significant in children with meningitis, it is recommended that BERA be recorded in all, so that early intervention may be possible.

Glutaraldehyde cross-linking of lectins to marker enzymes: protection of binding site by specific sugars.

The role of bound specific sugars in protecting the sugar binding activity of several galactose binding proteins during their covalent conjugation to horse radish peroxidase by glutaraldehyde-mediated cross-linking was examined by: a) affinity matrix binding of the conjugate, b) enzyme linked lectin assay and c) hemagglutination assay. During conjugation using 1% glutaraldehyde, protection of jack fruit (Artocarpus integrifolia) lectin (jacalin) activity depended on concentration of specific sugar present during conjugation; optimum protection was offered by 50 mM galactose. This indicated the presence of one or more primary groups at the binding site of jacalin, which is (are) essential for sugar binding. On the other hand, such essential amino group(s) was not indicated at the sugar binding site of the peanut lectin, bovine heart galectin or of the human serum anti alpha-galactoside antibody, since exclusion of sugar during their conjugation to HRP did not diminish sugar binding activity. The differential behavior is discussed in the light of reported differences in sugar specificities. Results indicated that sugar mediated blocking of active site may be used in characterization of the latter in lectins.

Perinatal mortality at a tertiary care hospital in Punjab.

The present report is a comparative analysis of perinatal mortality rate (PNMR) over two different periods of seven years each viz. 1982-1988 and 1989-1995. Data of all the perinatal deaths in babies born at Christian Medical College and Hospital, Ludhiana from January 1989 to December 1995 was collected. The cause of death was ascertained by a detailed history, clinical examination and whenever possible, by autopsy and analysed by modified Wigglesworth's classification. The PNMR during both the study periods was exactly the same i.e. 74/1000. There was a significant decline in the early neonatal mortality rate from 32/1000 to 25/1000. This was mainly due to improved survival of preterms as there were better life support measures available in the latter part of study period. In contrast, the still birth rate increased significantly from 42/1000 to 49/1000, thus neutralizing the fall of neonatal mortality. There was no change in the pattern of causes of death. Macerated still births occurring mainly in growth retarded babies and asphyxia remained the major causes of death. Mere provision of health services is not going to decrease PNMR. There is a need to educate 'the ultimate' consumers i.e. the women, for better utilization of these services. There is also an urgent need to sensitize and involve the medical practitioners imparting obstetrical services for solving these issues.

Poisoning in children: Indian scenario.

The retrospective data on childhood poisoning from eight regional hospitals in India has been reviewed. The demographic features and types of poisonings encountered have been compared. The analysis of the data indicated that pediatric poisonings constituted 0.23-3.3% of the total poisoning. The mortality ranged from 0.64-11.6% with highest being from Shimla. Accidental poisoning was common involving 50-90% of children below 5 years of age and males outnumbered the females. Suicidal poisoning was seen after 13 years of age and was due to drugs and household chemicals. One of the hospitals in Delhi recorded a very high incidence (66.6%) of drug poisoning in children. The drugs consumed belonged to phenothiazines, antiepileptics and antipyretics. Iron poisoning was seen in younger children. Kerosene was one of the causes of accidental poisoning at all hospitals except Shimla and rural Maharashtra were probably wood charcoal is widely used. Pesticide poisoning was more prevalent in Punjab and West Bengal whereas plant poisoning was very common in Shimla. Significant number of snake envenomation has been recorded from rural Maharashtra. Other less common accidental poisonings in children included alcohol, corrosives, heavy metals, rodenticides, detergents and disinfectants. Thus various regions in the country showed some variation in types and frequency of childhood poisoning which could be attributed to different geographical and socio-economic background.

Predictive utility of clinical and stool parameters in bacterial diarrhoea in children.

A prospective one year study was conducted on children between the ages of 1 month to 5 years hospitalised in the pediatric ward of Christian Medical College, Ludhiana, with the aim of determining the predictive utility of certain clinical and stool parameters in diagnosing bacterial diarrhoea. Among the 204 children enrolled in the study, fever was observed in 40% in both the culture positive and negative groups. Clinical features such as abdominal distension, vomiting and oliguria although had low positive predictive values, their negative predictive values were high. Among the stool parameters, watery consistency and pus cells > 5 HPF were significantly more often observed in culture positive cases. The presence of mucus and pus cells > 5 HPF had good sensitivity (70-80%) but poor specificity (27-40%), while the reverse was true of blood (sensitivity 23%, specificity 89%). Again the positive predictive values were uniformly low while the negative ones were high. In conclusion the clinical and stool parameters were found to be more useful by their absence than by their presence in excluding a positive stool culture.