Management of acute bacterial skin and skin structure infections in India: are we equipped to meet the challenges of the growing menace of methicillin-resistant Staphylococcus aureus?

Staphylococcus aureus (S. aureus) is a Gram-positive facultative anaerobic bacterium that colonizes the skin and nasal passages of humans. The incidence of invasive S. aureus infections has increased over the past decades and is associated with poor outcomes and high mortality rates. S. aureus is responsible for almost one-third of acute bacterial skin and skin structure infections with methicillin-resistant Staphylococcus aureus (MRSA) accounting for a large proportion of these. The S. aureus strains prevalent inIndia are more aggressive and there are recent reports of the emergence of the more virulent multidrug resistant lineages ST2371 and ST8. Management of these infections is complicated by the fact that antimicrobial stewardship is non-existent, the choice of treatment is often empirical and available treatment options are limited due to a high prevalence of resistance strains. Currently available anti-MRSA agents include vancomycin, teicoplanin, linezolid, daptomycin, tigecycline, and clindamycin. However, the emergence of resistant strains and several undesirable features related to the safety and tolerability of these agents have limited the options available for the management of MRSA infections. A newer, safe and efficacious antibiotic is thus an unmet need for the management of MRSA in patients with acute bacterial skin and skin structure infections. In this review we explore the current and future trends in the management of acute bacterial skin and skin structure infections highlighting the challenges in their management in India, and current progress in the development of some novel drugs for the management of MRSA infections.

An evaluation of safety and efficacy of nadifloxacin 1% ointment versus mupirocin 1% ointment in Indian children with skin and soft tissue infection

Background: Although nadifloxacin has been shown to be effective in the treatment of skin & soft tissue infections (SSTI), there is a paucity of data comparing its efficacy and safety with other antibacterials, especially in Indian paediatric population. Therefore, objective of this study was to compare the safety and efficacy of nadifloxacin with mupirocin in children with SSTI.Methods: This was a single-centre, open label, randomized, parallel group, comparative study in 60 children of <12 years of age with SSTI. Test group (n=30) received nadifloxacin 1% ointment and reference group (n=30) received mupirocin 1% ointment, to be applied twice daily. Patients were followed up at day 4, 8 and 15. Efficacy of the study drugs was evaluated by clinical and bacteriological cure rate. Safety was assessed by reporting of adverse events.Results: Baseline characteristics of enrolled patients were comparable between treatment groups and all 60 patients completed the study. At Day 15, 100.0% cases among nadifloxacin group and 96.7% cases among mupirocin group achieved clinical cure (p=0.313). The most common bacteria found in culture were Gram positive cocci in both the groups (86.7% in nadifloxacin and 58.8% in mupirocin group). None of the cases in any of the groups showed bacteriological presence at day 15. No adverse event was reported in any of the treatment groups during the study duration.Conclusions: Nadifloxacin was found to be equally efficacious and safe to mupirocin in the treatment of SSTI in Indian pediatric population.

Effectiveness and safety of pidotimod in recurrent respiratory infections in children: a pilot study

Background: Recurrent respiratory infections (RRIs) are common in children especially in age 1 to 6 years. Pidotimod, an immunostimulant has been found to lower the recurrences of RRIs and improve the quality of life. The Objective of this study was to assess the efficacy and safety of pidotimod in children with recurrent respiratory infections (RRIs).Methods: In this single-centre, prospective, observational study, children aged 2 to 15 years diagnosed with RRIs were included. RRIs were defined as occurrence of 3 or more episodes of acute respiratory infections (ARIs) or more than 15 days of respiratory symptoms in the past 3 months. These children were treated with pidotimod in addition to standard care treatment. Treatment duration was two months and the follow-up continued for three months. Number of RRIs and severity of RRIs, antibiotic courses and rate of hospitalization before and after treatment were compared.Results: In total 25 children included in the study, mean age was 7.34'3.63 years. Among them, 68% were males. After treatment with pidotimod, there was significant reduction in mean number of ARI episodes (3.84'0.85 at baseline to 0.48'0.51 at follow-up, p<0.0001). Also, there was significant reduction in the duration of acute infectious episodes (p<0.0001), need of antibiotic courses (p<0.0001) and rates of hospitalization (p<0.0001). No safety concerns were identified and pidotimod was well tolerated.Conclusions: Addition of pidotimod to the standard treatment in children with RRIs significantly reduces the recurrence, duration of repeat infectious episodes, need of antibiotic treatments and future rates of hospitalizations. These findings support previous data.

Current clinical trends in the management of gram positive infections in Indian critical care settings: a survey

Background: In India, gram-positive infections (GPIs) particularly, methicillin-resistant Staphylococcus aureus (MRSA) prevalence is reported to increase exponentially. The overall mortality rate among patients with multi drug resistant GPIs in ICU setting are as high as 16%, despite the availability of various therapeutic options. Aim of the study is to determine the burden of GPIs in critical care settings and to understand the practising behaviour among the specialists in the management of MRSA infections.Methods: The survey was conducted among 264 critical care specialists who attended the Annual National Conference of Indian Society of Critical Medicine held in February 2019 at Mumbai. The delegates were administered a validated 10 question survey.Results: In the survey, 72% of the respondents agreed to the rising prevalence of MRSA and associated increased mortality rate of >16%. Empirical gram positive cover is being given to 30-40% of ICU patients, with ABSSSI being listed as a major indication followed by CAP, VAP, CLABSI and DFI. 46% of the doctors listed vancomycin as their preferred anti-MRSA agents followed by teicolplanin and linezolid. However, more than 80% of the doctors feel that nephrotoxicity in vancomycin, thrombocytopenia in linezolid and poor biofilm penetration are major limitations of these anti-MRSA agents.Conclusions: The survey highlighted the increasing trend in the prevalence and associated mortality in GPIs in critical care settings in India. Further, the limitations of existing anti-MRSA agents have invoked the need for a newer agent with a broad spectrum anti-bacterial activity along with improved safety profile and effective biofilm penetration, which can be used as a suitable alternative empiric therapy to manage GPIs.

Clinical challenges with excipients in insulin formulations and role of concentrated insulin

Most of the insulin formulations in clinical use contain phenol, meta-cresol or both as excipients. These excipients in insulin preparations provide stability and have antimicrobial properties. However, they are reported to be associated with undesirable side-effects especially localised allergic reactions. Amount of excipients injected per unit dose of insulin is a major determining factor in causation of these reactions. This review discusses the excipients in different insulin formulations available in India with potential of precipitating undesirable effects and the use of concentrated insulins to reduce these complications. To avoid the detrimental effects associated with excipients, removal of preservatives or use of insulin preparations devoid of excipients can be an option. Besides these approaches, one approach that can be considered is the use of concentrated insulin to reduce the volume of insulin dose and thereby the excipients. Concentrated insulins address the high insulin requirements of the growing population of patients with type 2 diabetes who require higher insulin doses. Concentrated insulins help in reduction of dose volume as well as amount of excipients injected per unit dose of insulin. U200 (concentrated r-DNA Human Insulin Premix 30/70-200 IU/ml) can be advantageous with better absorption from smaller quantity injected, lesser variability in absorption, lesser pain and discomfort due to smaller quantity, lesser chances of hypoglycaemia all of which can lead to better patient compliance. Thus, concentrated insulin U200 can be one of the alternatives to prevent/reduce clinical complications with excipients in insulins.

Salt sensitivity and its implication in clinical practice

Hypertension (HTN) is a complex multi-factorial disease and is considered one of the foremost modifiable risk factors for stroke, heart failure, ischemic heart disease and renal dysfunction. Over the past century, salt and its linkage to HTN and cardiovascular (CV) mortality has been the subject of intense scientific scrutiny. There is now consensus that different individuals have different susceptibilities to blood pressure (BP)-raising effects of salt and this susceptiveness is called as salt sensitivity. Several renal and extra-renal mechanisms are believed to play a role. Blunted activity of the renin–angiotensin–aldosterone system (RAAS), adrenal Rac1-MR-Sgk1-NCC/ENaC pathway, renal SNS-GR-WNK4-NCC pathway, defect of membrane ion transportation, inflammation and abnormalities of Na+/Ca2+ exchange have all been implicated as pathophysiological basis for salt sensitive HTN. While salt restriction is definitely beneficial recent observation suggests that treatment with Azilsartan may improve salt sensitivity by selectively reducing renal proximal tubule Na+/H+ exchange. This encourages the future potential benefits of recognizing and therapeutically addressing the salt sensitive phenotype in humans.