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Background: In India, states have licensed the manufacture of large numbers of fixed-dose combination (FDC) drugs without the required prior approval of the central regulator. This paper describes two major regulatory initiatives to address the problem, which began in 2007 and 2013, and examines whether they have been sufficient to remove centrally unapproved systemic antibiotic FDCs from the market. Methods: Information was extracted from documents published by the central regulator and the ministry of health, including the National List of Essential Medicines (NLEM), and court judgments, and analysed alongside sales volume data for 2008–2020 using PharmaTrac market dataset. Results: The regulatory initiatives permitted 68 formulations to be given de facto approvals ('No Objection Certificates') outside the statutory regime, banned 46 FDCs and restricted one FDC. Market data show that FDCs as a proportion of total antibiotic sales increased from 32.9 in 2008 to 37.3% in 2020. The total number of antibiotic FDC formulations on the market fell from 574 (2008) to 395 (2020). Formulations with a record of prior central approval increased from 86 (2008) to 94 (2020) and their share of the antibiotic FDC sales increased from 32.0 to 55.3%. In 2020, an additional 23 formulations had been permitted de facto approval, accounting for 10.6% of the antibiotic FDC sales. Even in 2020, most marketed formulations (70.4%, 278/395) were unapproved or banned, and comprised a 15.9% share of the antibiotic FDC sales. The share of NLEM-listed antibiotic FDC sales increased from 21.2 (2008) to 26.7% (2020). Conclusion: The initiatives had limited impact. Regulatory enforcement has been slow and weak, with many unapproved, and even banned, FDCs remaining on the market. [ABSTRACT FROM AUTHOR]

Purpose: To describe clinical features, demographic profile and factors predicting outcome of endophthalmitis under care progressing to panophthalmitis at a tertiary eye institute.Setting: Retrospective consecutive case series.Methods: All cases diagnosed as endophthalmitis of any etiology and undergoing treatment which progressed to panophthalmitis from January 2005 to December 2015 were included. Case records of all patients coded as endophthalmitis and then panophthalmitis were included. Data were collected regarding the clinical features, demographic profile, and treatment outcomes of those cases.Results: This study included 33 eyes of 33 patients. The mean age at presentation was 42.33 ± 21.66 years (median 40, range 5-75). The commonest etiology of endophthalmitis progressing to panophthalmitis was noted following open globe injury endophthalmitis, seen in 13/33 (39.4%) of eyes followed by endophthalmitis associated with microbial keratitis seen in 8/33 (27.3%) eyes. The time interval in days between the diagnosis of endophthalmitis and progression to panophthalmitis was 4.5 ± 3.88 days (median 3 days, range 1-14 days). Fifteen eyes denied perception of light (PL) at the time of diagnosing panophthalmitis. Culture was positive in 16 cases (48.4%), Streptococcus pneumoniae was the commonest species (4 cases) followed by Pseudomonas aeruginosa (3 cases) and Staphylococcus epidermidis (2 cases). Nine cases (27.27%) were additionally given systemic steroids along with the systemic antibiotics. The odds ratio of a favorable outcome was significantly higher when systemic steroids with antibiotics were administered (OR = 80.5, 95% C.I. 6.311026, p = 0.007), when the patient was of a younger age group (< 40 years) (OR 1.53, 95% C.I. 0.37.87, p = 0.6), when the presenting vision at diagnosis was at least light perception (OR 9.8, 95% C.I. 1.03692.7, p = 0.04), when the smear showed Gram-positive cocci (OR 6.66, 95% C.I. 1.0940.43, p = 0.03), if there was culture positivity (OR 10.5, 95% C.I. 1.1198.9, p = 0.03) and when intravenous antibiotics were administered (OR 21.43, 95% C.I. 1.11411.7, p = 0.04).Conclusions: Risk of progression of endophthalmitis to panophthalmitis is there even under care. Close observation and keen clinical examination for cases that do not respond well is essential. Intravenous antibiotics and systemic steroids should be considered in all cases of endophthalmitis that progress to panophthalmitis. [ABSTRACT FROM AUTHOR]