Authors’ response

Sir,

1. We appreciate the critical comments regarding our study conducted in 2011-20121. Our institute is a tertiary neuro care center and has a strict Hospital Infection Surveillance System which constantly monitors the MDR infections in the wards and Intensive Care Units. Also the percentages of drug-resistant isolates reported in our six-months study cannot be extrapolated to studies conducted in different hospitals receiving different types of specimen or studies conducted on particular infection sites. Studies quoted by the authors23 provide data from multicenter studies and give an excellent overview of drug resistance scenario in the country. However, these studies were conducted in 20033 and 20072 and might not be relevant to the percentages of our study (6 months data from one hospital in 2011-2012)1.

2. As part of routine laboratory screening of patients samples we performed the antibiotic sensitivity testing of the positive cultures as per CLSI guidelines4. We considered those isolates to be MDR, that were resistant to the first and second line antibiotics - depending on the samples. As mentioned in our study1, only those isolates resistant to the following panel of antibiotics by disk diffusion method were considered for further analysis as NDM-1 producers are known to have additional mechanisms that make them resistant to several classes of antibiotics:

   In micrograms, ampicillin (10), amikacin (30), gentamicin (10), ciprofloxacin (5), ofloxacin (5), cefotaxime (30), ceftriaxone (30), ceftazidime (30), imipenem (10), cefoperazone-sulbactam (75/10), piperacillin-tazobactam (100/19), aztreonam (30), cefepime (30), tobramycin (19). A similar panel of antibiotics has been tested in the SMART study conducted from 2002-20115.

   This is a tertiary care centre specializing in the central nervous system diseases and not having a considerable number of patients with other illnesses. Also, our hospital has a strict antibiotic policy and hospital infection surveillance system in place; which could be the main reason of our reduced rate of drug resistant bacteria as a whole.

3. The carbapenem antibiotic that was screened using disk diffusion method was imipenem. All 74 isolates were resistant to imipenem by Kirby-Bauer disk diffusion method. The other carbapenem antibiotics-meropenem and ertapenem were checked through the Vitek 2 Compact 60 system. For certain isolates Vitek had suppressed certain carbapenems from analysis.

   The MIC values of meropenem (ME), ertapenem (ERT) and imipenem (IPM) for the six PCR-positive, variable carbapenem resistant isolates are as follows:

4. The test that was performed for our study was the combined disk test or-imipenem - EDTA combined disk synergy test (CDST)6. We regret the possible confusion caused due to the wrong naming.

5. Table II has been referred to a particular section of the paper where all the calculations of percentages have been done according to the number of clinical specimens collected. The percentage of bla_ndm-1 carrying A. baumannii (n = 4; 5.7%) was calculated among the number of samples studied (n = 70). It would be 20 per cent when calculated among the total MDR isolates of the same bacterial species. The same is applicable to E. coli also. In our study, 14.7 per cent of NDM-1 positive isolates were E. coli (5 PCR +ve E. coli /34 total PCR +ve isolates). Here the calculation was done based on the number of isolates. There were instances when more than one isolate were retrieved from one tracheal aspirate sample and hence > 100 per cent value for the percentage of total number of isolates.

   For example, 45 isolates from 39 tracheal aspirate samples would give a percentage of 115.38 per cent. The Table was made in consultation with a biostatistician of the study centre.

6. The susceptibility to tigecycline was assessed based on Vitek system report. The two isolates were Providencia rettgeri (MIC=2 µg/ml) and Klebsiella pneumoniae ssp pneumoniae (MIC ≥ 8 µg/ml), both isolated from tracheal samples. In a recently published article7 it has been stated that according to EUCAST breakpoints (http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Disk_test_documents/EUCAST_breakpoints_v1.3_pdf.pdf) P. rettgeri can be considered resistant to tigecycline with MIC = 2 mg/l.