{"id":6805,"date":"2016-04-28T08:05:30","date_gmt":"2016-04-28T08:05:30","guid":{"rendered":"http:\/\/biomedpharmajournal.org\/?p=6805"},"modified":"2016-05-04T05:46:04","modified_gmt":"2016-05-04T05:46:04","slug":"pathogens-causing-urinary-tract-infection-in-children-and-their-in-vitro-susceptibility-to-antimicrobial-agents-a-hospital-based-study","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol9no1\/pathogens-causing-urinary-tract-infection-in-children-and-their-in-vitro-susceptibility-to-antimicrobial-agents-a-hospital-based-study\/","title":{"rendered":"Pathogens Causing Urinary Tract Infection In Children and Their In Vitro Susceptibility to Antimicrobial Agents- A Hospital Based Study"},"content":{"rendered":"<p><strong>Introduction<\/strong><\/p>\n<p>Urinary tract infection (UTI) is one of the most common infections in children associated with significant complications like scarring of kidney, hypertension, and chronic kidney disease<sup>1<\/sup>. Gram-negative bacilli are the most common cause of pediatric UTI especially <em>Escherichia coli<\/em> responsible for more than 90% of uncomplicated UTI<sup>2<\/sup>. Enterococcus, Klebsiella and Coagulase negative Staphylococcus aureus (CoNS) are other organisms sharing remaining burden of UTI. Antibiotics have been the mainstay of treatment of UTI. Antibiotic resistance has become a major global problem especially in India where 80% of <em>E.coli<\/em> is resistant to penicillins, cephalosporins and quinolones (http:\/\/www.cddep.org\/resistancemap\/). Treatment of UTI is becoming difficult because of the antibiotic resistance in bacteria especially with <em>E.coli<\/em>producing extended spectrum \u00df-lactamases (ESBLs). Our study aims to identify common pathogens causing UTI in children, their in vitro antibiotic susceptibility pattern to commonly used antibiotics in a clinical setting in India. These findings will help us in deciding the empirical choice of antibiotics for children presenting with UTI, thus preventing treatment failure and decreasing the drug resistance rates.<\/p>\n<p><strong>Table 1:\u00a0 Number and proportion of isolated pathogens (Gram negative and Gram positive pathogen) from midstream urine species<\/strong><\/p>\n<table style=\"width: 95%;\" border=\"1\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td style=\"text-align: center;\" colspan=\"3\" width=\"342\"><strong>Gram negative bacteria<\/strong><\/td>\n<td style=\"text-align: center;\" colspan=\"3\" width=\"341\"><strong>Gram positive bacteria<\/strong><\/td>\n<\/tr>\n<tr>\n<td width=\"188\">Bacteria Species<\/td>\n<td width=\"56\">n<\/td>\n<td width=\"98\">Percent<\/td>\n<td width=\"212\">Bacteria Species<\/td>\n<td width=\"63\">n<\/td>\n<td width=\"67\">Percent<\/td>\n<\/tr>\n<tr>\n<td width=\"188\">Escherichia coli<\/td>\n<td width=\"56\">53<\/td>\n<td width=\"98\">40.8%<\/td>\n<td width=\"212\">Enterococcus species<\/td>\n<td width=\"63\">29<\/td>\n<td width=\"67\">24.6 %<\/td>\n<\/tr>\n<tr>\n<td width=\"188\">Klebsiella species<\/td>\n<td width=\"56\">22<\/td>\n<td width=\"98\">17 %<\/td>\n<td width=\"212\">Coagulase Negative Staphylococcus (CoNS)<\/td>\n<td width=\"63\">5<\/td>\n<td width=\"67\">3.8%<\/td>\n<\/tr>\n<tr>\n<td width=\"188\">Proteus species<\/td>\n<td width=\"56\">14<\/td>\n<td width=\"98\">10.8%<\/td>\n<td colspan=\"3\" rowspan=\"4\" width=\"341\"><\/td>\n<\/tr>\n<tr>\n<td width=\"188\">Enterobacter species<\/td>\n<td width=\"56\">&#8211;<\/td>\n<td width=\"98\"><\/td>\n<\/tr>\n<tr>\n<td width=\"188\">Pseudomonas aeruginosa<\/td>\n<td width=\"56\">4<\/td>\n<td width=\"98\">3.1%<\/td>\n<\/tr>\n<tr>\n<td width=\"188\">Acinetobacter species<\/td>\n<td width=\"56\">1<\/td>\n<td width=\"98\">0.8%<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p><strong>Design and setting<\/strong><\/p>\n<p>It was a retrospective observational study collecting data from hospital records during the period of January 2015 &#8211; December 2015 in SRM medical college hospital &amp; research centre. Urine culture reports of all pediatric patients with suspected UTI admitted in SRM hospital during that period were reviewed.<\/p>\n<p><strong>Inclusion criteria\u00a0<\/strong>All children with suspected UTI and whose urine culture shows single pathogen with colony counts higher than or equal to 10<sup>5 <\/sup>colony forming units (CFU)\/ml were included for the study.<\/p>\n<p><strong>Table 2: The distribution of pathogens in patients according to gender<\/strong><\/p>\n<table style=\"width: 95%;\" border=\"1\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td style=\"text-align: center;\" width=\"215\"><strong>\u00a0<\/strong><\/td>\n<td style=\"text-align: center;\" colspan=\"2\" width=\"218\"><strong>Boys<\/strong><\/td>\n<td style=\"text-align: center;\" colspan=\"2\" width=\"230\"><strong>Girls<\/strong><\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Bacteria<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/td>\n<td width=\"109\">Number of patients<\/td>\n<td width=\"109\">Percent<\/td>\n<td width=\"121\">Number of<\/p>\n<p>patients<\/td>\n<td width=\"109\">Percent<\/p>\n<p>&nbsp;<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Escherichia coli<\/td>\n<td width=\"109\">23<\/td>\n<td width=\"109\">43.4 %<\/td>\n<td width=\"121\">30<\/td>\n<td width=\"109\">56.6 %<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Klebsiella species<\/td>\n<td width=\"109\">20<\/td>\n<td width=\"109\">59.1 %<\/td>\n<td width=\"121\">9<\/td>\n<td width=\"109\">40.9 %<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Proteus species<\/td>\n<td width=\"109\">14<\/td>\n<td width=\"109\">100 %<\/td>\n<td width=\"121\">&#8211;<\/td>\n<td width=\"109\">&#8211;<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Enterobacter species<\/td>\n<td width=\"109\">&#8211;<\/td>\n<td width=\"109\">&#8211;<\/td>\n<td width=\"121\">&#8211;<\/td>\n<td width=\"109\">&#8211;<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Pseudomonas aeruginosa<\/td>\n<td width=\"109\">&#8211;<\/p>\n<p>&nbsp;<\/td>\n<td width=\"109\">&#8211;<\/td>\n<td width=\"121\">&#8211;<\/td>\n<td width=\"109\">&#8211;<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Acinetobacter species<\/td>\n<td width=\"109\">1<\/td>\n<td width=\"109\">100 %<\/td>\n<td width=\"121\">&#8211;<\/td>\n<td width=\"109\">&#8211;<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Enterococcus species<\/td>\n<td width=\"109\">20<\/td>\n<td width=\"109\">\u00a069 %<\/td>\n<td width=\"121\">9<\/td>\n<td width=\"109\">31.03 %<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Coagulase Negative Staphylococcus (CoNS)<\/td>\n<td width=\"109\">02<\/td>\n<td width=\"109\">40%<\/td>\n<td width=\"121\">3<\/td>\n<td width=\"109\">60%<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p><strong>Exclusion Criteria\u00a0<\/strong>Results of urine cultures without growth, multiple pathogens in urine culture, colony counts less than 10<sup>5 <\/sup>colony forming units (CFU)\/ml were excluded from the study.<\/p>\n<p><strong>Antibiotics and reagents<\/strong><\/p>\n<p>Urine culture was done semi-quantitatively on 5% sheep Blood Agar and MacConkey Agar plates incubated at 37\u00b0C overnight. Standard technique for semi-quantitative culture of urine was applied for colony count. After identification of organism antimicrobial susceptibility testing of the bacterial isolates was performed by Kirby Bauer\u2019s disk diffusion method using commercial antibiotic disks (Himedia, India) as per the Clinical and Laboratory Standards Institute (CLSI) guidelines<sup>3<\/sup>. The list of antibiotics used was appropriate for the urine sample and the type of organism (Gram positive\/gram negative). ESBL-producing <em>E.coli<\/em>, were detected using a double-disc synergy test.<\/p>\n<p>It included Ampicillin (10\u00b5g), Amikacin (30\u00b5g), amoxicillin\/ clavulanic acid (30\u00b5g+10\u00b5g), Cefotaxime (30\u00b5g), Cefepime (30\u00b5g), Ceftazidime (30\u00b5g), Ceftazidime+Clavulanic acid (30\u00b5g+10\u00b5g), Cefeperazone\/sulbactam (75\/30\u00b5g), Cefpodoxime (10\u00b5g), Ceftriaxone (30\u00b5g), Cefuroxime (30\u00b5g), Cefoxitin (30\u00b5g), Ciprofloxacin (5\u00b5g), Co-trimoxazole (25\u00b5g), Gentamicin (10\u00b5g), Imipenem (10\u00b5g),\u00a0 Meropenem (10\u00b5g), Nitrofurantoin (300\u00b5g), Norfloxacin (10\u00b5g), Ofloxacin (5\u00b5g), Piperacillin\/Tazobactam(100\u00b5g).<\/p>\n<p>The <em>Eschericia coli<\/em> ATCC 25922, <em>Pseudomonas aeruginosa<\/em> ATCC 27853 , <em>Staphylococcus aureus<\/em>ATCC 29213, <em>Enterococcus faecalis<\/em>ATCC 29212 strains were used as controls for the susceptibility testing of Enterobacteriacea, Nonfermenters, Staphylococcus species and Enterococcus species respectively. The interpretation of the zone diameters was done as per the CLSI break points<sup>13<\/sup>.<\/p>\n<p><strong>Table 3: Antibiotic susceptibility test results to antibiotics commonly used against ESBL- positive and ESBL-negative <em>Escherichia coli<\/em><\/strong><\/p>\n<table style=\"width: 95%;\" border=\"1\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td width=\"215\"><\/td>\n<td colspan=\"3\" width=\"217\">\n<p style=\"text-align: center;\"><strong>ESBL-positive Escherichia coli<\/strong><\/p>\n<p style=\"text-align: center;\"><strong>(n= 44)<\/strong><\/p>\n<\/td>\n<td style=\"text-align: center;\" colspan=\"3\" width=\"253\"><strong>\u00a0ESBL-negative\u00a0 Escherichia coli (n= 9)<\/strong><\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Antimicrobial drug<\/td>\n<td width=\"76\">S%<\/td>\n<td width=\"66\">I%<\/td>\n<td width=\"76\">R%<\/td>\n<td width=\"97\">S%<\/td>\n<td width=\"78\">I%<\/td>\n<td width=\"78\">R%<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Imipenem<\/td>\n<td width=\"76\">42(95.5)<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"76\">2(4.5)<\/td>\n<td width=\"97\">9 (100)<\/td>\n<td width=\"78\">&#8211;<\/td>\n<td width=\"78\">&#8211;<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Ciprofloxacin<\/td>\n<td width=\"76\">2 (4.5)<\/td>\n<td width=\"66\">1(2.3)<\/td>\n<td width=\"76\">41(93.2)<\/td>\n<td width=\"97\">7 (77.8)<\/td>\n<td width=\"78\">&#8211;<\/td>\n<td width=\"78\">2 (22.2)<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Nitrofurantoin<\/td>\n<td width=\"76\">40(90.9)<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"76\">4(9.1)<\/td>\n<td width=\"97\">8 (88.9)<\/td>\n<td width=\"78\">&#8211;<\/td>\n<td width=\"78\">1 (11.1)<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Meropenem<\/td>\n<td width=\"76\">42 (95.5)<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"76\">2 (4.5)<\/td>\n<td width=\"97\">9(100)<\/td>\n<td width=\"78\">&#8211;<\/td>\n<td width=\"78\">&#8211;<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">AmoxycillinClavulanic acid<\/td>\n<td width=\"76\">&#8211;<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"76\">44 (100)<\/td>\n<td width=\"97\">3 (33.3)<\/td>\n<td width=\"78\">&#8211;<\/td>\n<td width=\"78\">6 (66.7)<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Amikacin<\/td>\n<td width=\"76\">42 (95.5)<\/td>\n<td width=\"66\">1(2.3)<\/td>\n<td width=\"76\">1(2.3)<\/td>\n<td width=\"97\">9 (100)<\/td>\n<td width=\"78\">&#8211;<\/td>\n<td width=\"78\">&#8211;<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Gentamicin<\/td>\n<td width=\"76\">42(95.5)<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"76\">2(4.5)<\/td>\n<td width=\"97\">9 (100)<\/td>\n<td width=\"78\">&#8211;<\/td>\n<td width=\"78\">&#8211;<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">cefazolin<\/td>\n<td width=\"76\">&#8211;<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"76\">44 (100)<\/td>\n<td width=\"97\">6 (66.7)<\/td>\n<td width=\"78\">1(11.1)<\/td>\n<td width=\"78\">2(22.2)<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">cefepime<\/td>\n<td width=\"76\">4(9.1)<\/td>\n<td width=\"66\">1(2.3)<\/td>\n<td width=\"76\">39(88.6)<\/td>\n<td width=\"97\">3 (33.3)<\/td>\n<td width=\"78\">&#8211;<\/td>\n<td width=\"78\">6 (66.7)<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">cefotaxime<\/td>\n<td width=\"76\">&#8211;<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"76\">44(100)<\/td>\n<td width=\"97\">9 (100)<\/td>\n<td width=\"78\">&#8211;<\/td>\n<td width=\"78\">&#8211;<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Ceftazidime<\/td>\n<td width=\"76\">&#8211;<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"76\">44 (100)<\/td>\n<td width=\"97\">9 (100)<\/td>\n<td width=\"78\">&#8211;<\/td>\n<td width=\"78\">&#8211;<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">cefuroxime<\/td>\n<td width=\"76\">1(2.3)<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"76\">43(97.7)<\/td>\n<td width=\"97\">9 (100)<\/td>\n<td width=\"78\">&#8211;<\/td>\n<td width=\"78\">&#8211;<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Colistin<\/td>\n<td width=\"76\">44 (100)<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"76\">&#8211;<\/td>\n<td width=\"97\">9 (100)<\/td>\n<td width=\"78\"><\/td>\n<td width=\"78\"><\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Ertapenem<\/td>\n<td width=\"76\">43 (97.7)<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"76\">1(2.3)<\/td>\n<td width=\"97\">9 (100)<\/td>\n<td width=\"78\">&#8211;<\/td>\n<td width=\"78\">&#8211;<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Nalidixic acid<\/td>\n<td width=\"76\">&#8211;<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"76\">44(100)<\/td>\n<td width=\"97\">2 (22.2)<\/td>\n<td width=\"78\">&#8211;<\/td>\n<td width=\"78\">7 (77.8)<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Netilmycin<\/td>\n<td width=\"76\">41(93.2)<\/td>\n<td width=\"66\">1(2.3)<\/td>\n<td width=\"76\">3(6.8)<\/td>\n<td width=\"97\">9 (100)<\/td>\n<td width=\"78\">&#8211;<\/td>\n<td width=\"78\">&#8211;<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Norfloxacin<\/td>\n<td width=\"76\">13(29.5)<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"76\">31(70.5)<\/td>\n<td width=\"97\">9 (100)<\/td>\n<td width=\"78\">&#8211;<\/td>\n<td width=\"78\">&#8211;<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Piperacillin\/Tazobactum<\/td>\n<td width=\"76\">34(77.3)<\/td>\n<td width=\"66\">3(6.8)<\/td>\n<td width=\"76\">7(15.9)<\/td>\n<td width=\"97\">9 (100)<\/td>\n<td width=\"78\">&#8211;<\/td>\n<td width=\"78\">&#8211;<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Co-trimoxazole<\/td>\n<td width=\"76\">8(18.2)<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"76\">38(86.4)<\/td>\n<td width=\"97\">4 (44.4)<\/td>\n<td width=\"78\">&#8211;<\/td>\n<td width=\"78\">5 (55.5)<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Ampicillin<\/td>\n<td width=\"76\">&#8211;<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"76\">44 (100)<\/td>\n<td width=\"97\">3 (33.3)<\/td>\n<td width=\"78\">&#8211;<\/td>\n<td width=\"78\">6 (66.7)<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Ceftriaxone<\/td>\n<td width=\"76\"><\/td>\n<td width=\"66\">1 (2.3)<\/td>\n<td width=\"76\">43 (97.7)<\/td>\n<td width=\"97\">9(100)<\/td>\n<td width=\"78\">&#8211;<\/td>\n<td width=\"78\">&#8211;<\/td>\n<\/tr>\n<tr>\n<td width=\"215\">Cefaperazonesulbactum<\/td>\n<td width=\"76\">38(86.4)<\/td>\n<td width=\"66\">3 (6.8)<\/td>\n<td width=\"76\">3 (6.8)<\/td>\n<td width=\"97\">9 (100)<\/td>\n<td width=\"78\">&#8211;<\/td>\n<td width=\"78\">&#8211;<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>*S%- Percentage sensitive, I%- Percentage Intermediate Sensitive, R%- Percentage Resistant<\/p>\n<p><strong>Results<\/strong><\/p>\n<p>About 551 urine samples from suspected UTI children were subjected to culture and antibiotic susceptibility testing by Kirby Bauer Disc diffusion method. About 130 were culture-positive, had significant colony count and included in the final analysis. <em>E coli<\/em> was detected in 40.8 % of cultures, followed by Enterococcus spp (22.3%), Klebsiellaspp (17.0%), Proteus spp (10.8%), Coagulase negative Staphylococcus (3.8%), Pseudomonas (3.1%), and Acinetobacter (0.8%). The detection rate of ESBL-producing <em>E coli<\/em> was 83%. <em>E.coli<\/em>&amp;Klebsiella were almost equally distributed among both sexes but all cases of Proteus and most cases of Enterococcus (69%) occurred in males.<\/p>\n<p>Most Gram negative bacteria were sensitive to Aminoglycosides and Carbapenams and Gram positive bacteria were sensitive to Vancomycin and Linezolid. ESBL positive <em>E.coli<\/em> was more problematic with resistance to Amoxycillin\/clavulanic acid, Cephalosporins and Quinolones. They were also not uniformly sensitive to Piperacillin\/Tazobactum (77.3%), Cefoperazone\/Sulbactum (86.4%) as ESBL negative <em>E.Coli.<\/em>Nalidixic acid resistance which is considered as a marker of fluoroquinolone resistance ranges from 100% in ESBL positive <em>E.coli<\/em>to 25% in Klebsiella. The surprise drug has been Nitrofurantoin with ESBL positive <em>E.coli, <\/em>Enterococcus &amp; Coagulase Negative Staphylococcus being sensitive. Not only in ESBL positive <em>E.coli<\/em>, cephalosporin resistance was observed one in three times in Klebsiella and 80% resistance to Cefazolin was seen in Proteus. Also Trimethoprim\/Sulfamethoxazole resistance was high in the range of 35%-86% among various enterobacteraciaea.<\/p>\n<p><strong>Table 4 : Antibiotic susceptibility test results to antibiotics commonly used against Klebsiellasppand Proteus spp.<\/strong><\/p>\n<table style=\"width: 95%;\" border=\"1\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td style=\"text-align: center;\" rowspan=\"2\" width=\"172\">&nbsp;<\/p>\n<p><strong>Antimicrobial drug<\/strong><\/td>\n<td style=\"text-align: center;\" colspan=\"3\" width=\"217\"><strong>Klebsiellaspp, n= 22<\/strong><\/td>\n<td style=\"text-align: center;\" colspan=\"4\" width=\"228\"><strong>Proteus spp, n=14<\/strong><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"77\"><strong>S%<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"72\"><strong>I%<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"68\"><strong>R%<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"82\"><strong>S%<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"73\"><strong>I%<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"73\"><strong>R%<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"1\"><strong>\u00a0<\/strong><\/td>\n<\/tr>\n<tr>\n<td width=\"172\">Imipenem<\/td>\n<td width=\"77\">21 (95.5)<\/td>\n<td width=\"72\">1 (4.5)<\/td>\n<td width=\"68\">&#8211;<\/td>\n<td width=\"82\">14 (100)<\/td>\n<td width=\"73\">_<\/td>\n<td width=\"73\">&#8211;<\/td>\n<td width=\"1\"><\/td>\n<\/tr>\n<tr>\n<td width=\"172\">Ciprofloxacin<\/td>\n<td width=\"77\">21(95.5)<\/td>\n<td width=\"72\">&#8211;<\/td>\n<td width=\"68\">1(4.5)<\/td>\n<td width=\"82\">9 (64.3)<\/td>\n<td width=\"73\">2 (14.3)<\/td>\n<td width=\"73\">3 (21.4)<\/td>\n<td width=\"1\"><\/td>\n<\/tr>\n<tr>\n<td width=\"172\">Nitrofurantoin<\/td>\n<td width=\"77\">13 (59.1)<\/td>\n<td width=\"72\">7 (31.8)<\/td>\n<td width=\"68\">2 (9.1)<\/td>\n<td width=\"82\">7 (50)<\/td>\n<td width=\"73\">2 (14.3)<\/td>\n<td width=\"73\">5(35.7)<\/td>\n<td width=\"1\"><\/td>\n<\/tr>\n<tr>\n<td width=\"172\">Meropenem<\/td>\n<td width=\"77\">22 (100)<\/td>\n<td width=\"72\">&#8211;<\/td>\n<td width=\"68\">&#8211;<\/td>\n<td width=\"82\">14 (100)<\/td>\n<td width=\"73\">&#8211;<\/td>\n<td width=\"73\">&#8211;<\/td>\n<td width=\"1\"><\/td>\n<\/tr>\n<tr>\n<td width=\"172\">Amikacin<\/td>\n<td width=\"77\">21(95.5)<\/td>\n<td width=\"72\">&#8211;<\/td>\n<td width=\"68\">1(4.5)<\/td>\n<td width=\"82\">13 (92.9)<\/td>\n<td width=\"73\">1 (7.1)<\/td>\n<td width=\"73\">&#8211;<\/td>\n<td width=\"1\"><\/td>\n<\/tr>\n<tr>\n<td width=\"172\">Gentamicin<\/td>\n<td width=\"77\">21(95.5)<\/td>\n<td width=\"72\">&#8211;<\/td>\n<td width=\"68\">1(4.5)<\/td>\n<td width=\"82\">14(100)<\/td>\n<td width=\"73\">&#8211;<\/td>\n<td width=\"73\">&#8211;<\/td>\n<td width=\"1\"><\/td>\n<\/tr>\n<tr>\n<td width=\"172\">Cefazolin<\/td>\n<td width=\"77\">13 (59.1)<\/td>\n<td width=\"72\">&#8211;<\/td>\n<td width=\"68\">9 (40.9)<\/td>\n<td width=\"82\">14 (100)<\/td>\n<td width=\"73\">&#8211;<\/td>\n<td width=\"73\">&#8211;<\/td>\n<td width=\"1\"><\/td>\n<\/tr>\n<tr>\n<td width=\"172\">Cefepime<\/td>\n<td width=\"77\">14 (63.6)<\/td>\n<td width=\"72\">1(4.5)<\/td>\n<td width=\"68\">7(31.8)<\/td>\n<td width=\"82\">3 (21.4)<\/td>\n<td width=\"73\">2 (14.3)<\/td>\n<td width=\"73\">9(64.3)<\/td>\n<td width=\"1\"><\/td>\n<\/tr>\n<tr>\n<td width=\"172\">Cefotaxime<\/td>\n<td width=\"77\">14(63.6)<\/td>\n<td width=\"72\">&#8211;<\/td>\n<td width=\"68\">8(36.4)<\/td>\n<td width=\"82\">11(78.6)<\/td>\n<td width=\"73\">&#8211;<\/td>\n<td width=\"73\">3(21.4)<\/td>\n<td width=\"1\"><\/td>\n<\/tr>\n<tr>\n<td width=\"172\">Ceftazidime<\/td>\n<td width=\"77\">14(63.6)<\/td>\n<td width=\"72\">&#8211;<\/td>\n<td width=\"68\">8(36.4)<\/td>\n<td width=\"82\">12 (85.7)<\/td>\n<td width=\"73\">&#8211;<\/td>\n<td width=\"73\">2 (14.3)<\/td>\n<td width=\"1\"><\/td>\n<\/tr>\n<tr>\n<td width=\"172\">Cefuroxime<\/td>\n<td width=\"77\">15(68.2)<\/td>\n<td width=\"72\">&#8211;<\/td>\n<td width=\"68\">7(31.8)<\/td>\n<td width=\"82\">14 (100)<\/td>\n<td width=\"73\">&#8211;<\/td>\n<td width=\"73\">&#8211;<\/td>\n<td width=\"1\"><\/td>\n<\/tr>\n<tr>\n<td width=\"172\">Colistin<\/td>\n<td width=\"77\">11(50)<\/td>\n<td width=\"72\">&#8211;<\/td>\n<td width=\"68\">&#8211;<\/td>\n<td width=\"82\">7(50)<\/td>\n<td width=\"73\">4(18.2)<\/td>\n<td width=\"73\">3(21.4)<\/td>\n<td width=\"1\"><\/td>\n<\/tr>\n<tr>\n<td width=\"172\">Ertapenem<\/td>\n<td width=\"77\">21(95.5)<\/td>\n<td width=\"72\">&#8211;<\/td>\n<td width=\"68\">1(4.5)<\/td>\n<td width=\"82\">14(100)<\/td>\n<td width=\"73\">&#8211;<\/td>\n<td width=\"73\">&#8211;<\/td>\n<td width=\"1\"><\/td>\n<\/tr>\n<tr>\n<td width=\"172\">Nalidixic acid<\/td>\n<td width=\"77\">15 (68.2)<\/td>\n<td width=\"72\">2(9.1)<\/td>\n<td width=\"68\">5(22.7)<\/td>\n<td width=\"82\">9(40.9)<\/td>\n<td width=\"73\">1(7.1)<\/td>\n<td width=\"73\">4(18.2)<\/td>\n<td width=\"1\"><\/td>\n<\/tr>\n<tr>\n<td width=\"172\">Netilmycin<\/td>\n<td width=\"77\">20 (90.9)<\/td>\n<td width=\"72\">1(4.5)<\/td>\n<td width=\"68\">1 (4.5)<\/td>\n<td width=\"82\">13(92.9)<\/td>\n<td width=\"73\">&#8211;<\/td>\n<td width=\"73\">1 (7.1)<\/td>\n<td width=\"1\"><\/td>\n<\/tr>\n<tr>\n<td width=\"172\">Norfloxacin<\/td>\n<td width=\"77\">18(81.8)<\/td>\n<td width=\"72\">3(13.6)<\/td>\n<td width=\"68\">1(4.5)<\/td>\n<td width=\"82\">11(78.6)<\/td>\n<td width=\"73\">1(7.1)<\/td>\n<td width=\"73\">2(14.3)<\/td>\n<td width=\"1\"><\/td>\n<\/tr>\n<tr>\n<td width=\"172\">Piperacillin\/Tazobactum<\/td>\n<td width=\"77\">19(86.4)<\/td>\n<td width=\"72\">2(9.1)<\/td>\n<td width=\"68\">1(4.5)<\/td>\n<td width=\"82\">14 (100)<\/td>\n<td width=\"73\">&#8211;<\/td>\n<td width=\"73\">&#8211;<\/td>\n<td width=\"1\"><\/td>\n<\/tr>\n<tr>\n<td width=\"172\">Co-trimoxazole<\/td>\n<td width=\"77\">14(63.6)<\/td>\n<td width=\"72\">&#8211;<\/td>\n<td width=\"68\">8(36.4)<\/td>\n<td width=\"82\">4(28.6)<\/td>\n<td width=\"73\">1(7.1)<\/td>\n<td width=\"73\">9(64.3)<\/td>\n<td width=\"1\"><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p><strong>\u00a0<\/strong>*S%- Percentage sensitive, I%- Percentage Intermediate Sensitive, R%- Percentage Resistant<\/p>\n<p><strong>Discussion\u00a0<\/strong><\/p>\n<p>This studydescribes one year susceptibility pattern of microorganisms causing UTI in pediatric population in SRM hospital. Male preponderance (62%) was there in our study. <em>E.coli<\/em> (40.8%) was the most common bacteria grown followed by Enterococcus (24.6%) and Klebsiella (17.0%). Studies done earlier also suggest a similar pattern<sup>4-6<\/sup>. However in our study 83% of E.coliwere ESBL producers, higher than what has been reported by other studies.<\/p>\n<p><strong><em>E.coli<\/em><\/strong><strong> treatment options<\/strong><\/p>\n<p><em>E.coli<\/em> arising from gut flora and causing UTI is a real challenge to clinicians because of the production of ESBL. Due to indiscriminate usage of antibiotics, <em>E.coli<\/em> in the gut are exposed to multiple drugs and due to selective pressure develop resistance against them. Plasmids transmit such drug resistance genes to remaining bacteria<sup>7<\/sup>. Our susceptibility results suggest that ESBL positive <em>E.coli<\/em>are resistant to more number of commonly used antibiotics than ESBL negative <em>E.coli<\/em>.<\/p>\n<p>We are now facing a situation where we don\u2019t have a good oral antibiotic against <em>E.coli<\/em> with no option of quinolones, cephaosporins and penicillins. One ray of hope is orally available Nitrofurantoin which is still sensitive against ESBL positive <em>E.coli<\/em>(91%). At present Nitrofurantoin can be given empirically for uncomplicated UTIs but studies related to its efficacy in complicated UTI is not convincing.<\/p>\n<p>Aminoglycosides can be recommended as initial empiric choice parenterally for ESBL positive <em>E.coli<\/em>although nephrotoxic potential has to be kept in mind. Usually a resistance of 20% is taken as the threshold for changing the empirical treatment of UTI<sup>8<\/sup>. Based on this recommendation, eventhoughPiperacillin\/Tazobactum (15.9% resistance) and Cefoperazone\/Sulbactum (6.8% resistance) are not uniformly sensitive, still can be recommended as first choices for ESBL positive <em>E.coli<\/em>. Carbapenams should be reserved as the final choice when patients fail to respond to the above antibiotics.<\/p>\n<p><strong>Table 5 : Antibiotic susceptibility test results to antibiotics commonly used against CoNSand Enterococcus spp<\/strong><\/p>\n<table style=\"width: 95%;\" border=\"1\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td width=\"113\"><\/td>\n<td style=\"text-align: center;\" colspan=\"3\" width=\"189\"><strong>CoNS , n= 5<\/strong><\/td>\n<td style=\"text-align: center;\" colspan=\"4\" width=\"356\"><strong>Enterococcus spp, n=29<\/strong><\/td>\n<\/tr>\n<tr>\n<td width=\"113\">Antimicrobial drug<\/td>\n<td width=\"66\">S%<\/td>\n<td width=\"57\">I%<\/td>\n<td width=\"66\">R%<\/td>\n<td width=\"113\">\u00a0 Antimicrobial drug<\/td>\n<td width=\"85\">S%<\/td>\n<td width=\"74\">I%<\/td>\n<td width=\"83\">R%<\/td>\n<\/tr>\n<tr>\n<td width=\"113\">Amikacin<\/td>\n<td width=\"66\">5 (100)<\/td>\n<td width=\"57\">&#8211;<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"113\">Ampicillin<\/td>\n<td width=\"85\">20 (69)<\/td>\n<td width=\"74\">3(10.3)<\/td>\n<td width=\"83\">6(20.7)<\/td>\n<\/tr>\n<tr>\n<td width=\"113\">Cefazolin<\/td>\n<td width=\"66\">4 (80)<\/td>\n<td width=\"57\">&#8211;<\/td>\n<td width=\"66\">1(20)<\/td>\n<td width=\"113\">Gentamicin (High level)<\/td>\n<td width=\"85\">14(48.3)<\/td>\n<td width=\"74\">&#8211;<\/td>\n<td width=\"83\">15(51.7)<\/td>\n<\/tr>\n<tr>\n<td width=\"113\">Ciprofloxacin<\/td>\n<td width=\"66\">2(40)<\/td>\n<td width=\"57\">&#8211;<\/td>\n<td width=\"66\">3(60)<\/td>\n<td width=\"113\">Linezolide<\/td>\n<td width=\"85\">28(96.6)<\/td>\n<td width=\"74\">&#8211;<\/td>\n<td width=\"83\">1(3.4)<\/td>\n<\/tr>\n<tr>\n<td width=\"113\">Gentamicin<\/td>\n<td width=\"66\">5(100)<\/td>\n<td width=\"57\">&#8211;<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"113\">Nitrofurantoin<\/td>\n<td width=\"85\">26(89.7)<\/td>\n<td width=\"74\">1(3.4)<\/td>\n<td width=\"83\">1(3.4)<\/td>\n<\/tr>\n<tr>\n<td width=\"113\">Linezolide<\/td>\n<td width=\"66\">5(100)<\/td>\n<td width=\"57\">&#8211;<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"113\">Penicillin<\/td>\n<td width=\"85\">21(72.4)<\/td>\n<td width=\"74\">&#8211;<\/td>\n<td width=\"83\">8(27.6)<\/td>\n<\/tr>\n<tr>\n<td width=\"113\">Nitrofurantoin<\/td>\n<td width=\"66\">5(100)<\/td>\n<td width=\"57\">&#8211;<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"113\">Tetracyclin<\/td>\n<td width=\"85\">28(96.6)<\/td>\n<td width=\"74\">1(3.4)<\/td>\n<td width=\"83\">&#8211;<\/td>\n<\/tr>\n<tr>\n<td width=\"113\">Norfloxacin<\/td>\n<td width=\"66\">5(100)<\/td>\n<td width=\"57\">&#8211;<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"113\">Vancomycin<\/td>\n<td width=\"85\">26(89.7)<\/td>\n<td width=\"74\">2(6.9)<\/td>\n<td width=\"83\">1(3.4)<\/td>\n<\/tr>\n<tr>\n<td width=\"113\">Penicillin<\/td>\n<td width=\"66\">&#8211;<\/td>\n<td width=\"57\">&#8211;<\/td>\n<td width=\"66\">5(100)<\/td>\n<td colspan=\"4\" rowspan=\"5\" width=\"356\"><\/td>\n<\/tr>\n<tr>\n<td width=\"113\">Rifampicin<\/td>\n<td width=\"66\">5(100)<\/td>\n<td width=\"57\">&#8211;<\/td>\n<td width=\"66\">&#8211;<\/td>\n<\/tr>\n<tr>\n<td width=\"113\">Tetracyclin<\/td>\n<td width=\"66\">4(80)<\/td>\n<td width=\"57\">1(20)<\/td>\n<td width=\"66\">&#8211;<\/td>\n<\/tr>\n<tr>\n<td width=\"113\">Cotrimoxzole<\/td>\n<td width=\"66\">2(40)<\/td>\n<td width=\"57\">1(20)<\/td>\n<td width=\"66\">2(40)<\/td>\n<\/tr>\n<tr>\n<td width=\"113\">Vancomycin<\/td>\n<td width=\"66\">5(100)<\/td>\n<td width=\"57\">&#8211;<\/td>\n<td width=\"66\">&#8211;<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>*S%- Percentage sensitive, I%- Percentage Intermediate Sensitive, R%- Percentage Resistant\u00a0CoNS- Coagulase Negative Staphylococcus<\/p>\n<p><strong>Klebsiella treatment options<\/strong><\/p>\n<p>Nine percentage resistance with Nitrofurantoin makes it an oral option for UTI due to Klebsiella. Quinolones may be recommended with caution because Norfloxacin(4.5%) resistance is low but Nalidixic acid resistance (22.7%) is higher. Few patients may not respond invivo to quinolones. Cephalosporins are poor choices as more than 30% resistance to cephalosporins is seen. Aminoglycosides and Piperacillin\/Tazobactum should be the empiric first choice parenteral antibiotics.<\/p>\n<p><strong>Proteus treatment options<\/strong><\/p>\n<p>Resistance to Nitrofurantoin (35.7%) is high and hence cannot be recommended as an oral option but AmoxycillinClavulanic acid can be tried orally since it is 100% sensitive. Aminoglycosides, Cefazolin and Piperacillin\/Tazobactum should be the empiric parenteral choices.<\/p>\n<p><strong>Gram positive bacteria- treatment options\u00a0<\/strong><\/p>\n<p>Coagulase Negative Staphylococcus (CONS) and Enterococcus were highly sensitive to Nitrofurantoin, Linezolid and Vancomycin. Hence uncomplicated UTI may be treated with oral Nitrofurantoin and complicated ones with parenteral Vancomycin and Linezolid.<\/p>\n<p><strong>Combating antibiotic resistance<\/strong><\/p>\n<p>The last time when an antibiotic was approved for gram negative sepsis was in 1973 and it was trimethoprim\/sulfamethoxazole. Our research is unable to catch the pace at which bacteria are relentlessly developing resistance. With no new antibiotic classes in the near future it is just a matter of time that they will develop resistance against all current options also.<\/p>\n<p>One option for combating resistance will be to explore promising drugs like fosfomycin, cycloserine and include them in our armamentarium. Fosfomycin is a phosphonic acid with broad spectrum Gram positive and Gram negative activity including Methicillin Resistant Staphylococcus Aureus (MRSA), Vancomycin Resistant Enterococcus (VRE) and Pseudomonas used often in Europe and US<sup>9, 10<\/sup>. However it has not yet been included in the list of antibiotics for susceptibility testing. Cycloserine which is used as second option for tuberculosis has been explored previously for UTI<sup>11<\/sup>. Since limited studies are available cycloserine can be studied further as an oral option.<\/p>\n<p>Other strategies like vaccination with orally administered Urovaxon<sup>R 12 <\/sup>and parenteral Strovac<sup>R 13<\/sup>, Probiotics<sup>15<\/sup>, Immune drugs<sup>14<\/sup> should be further researched as relying only on antibiotics may lead to disaster in the near future. Till then judicious and rational use of antibiotics based on culture and susceptibility patterns should be recommended.<\/p>\n<p><strong>Conclusion\u00a0<\/strong><\/p>\n<p>Our study shows that ESBL producing E.coli is the major pathogen causing UTI among pediatric population. Major cause of concern is that most of the organisms grown are resistant to three or more antibiotics. Oral Nitrofurantoin seems to be a promising oral option for uncomplicated UTI. Parenteral aminoglycosides, Piperacillin\/Tazobactum and Cefoperazone\/ Sulbactum can be given as first choice for Gram negative bacteria and parenteral Vancomycin, Linezolid for Gram positive bacteria. Carbapenams should be kept as reserve for patients who fail to respond with first choice antibiotics. Strict hospital antibiotic stewardship program should be in place which routinely reviews culture and susceptibility patterns and optimizes the selection and dosing accordingly.<\/p>\n<p><strong>Conflict of interest:<\/strong>\u00a0None<\/p>\n<p><strong>Source of funding<\/strong><\/p>\n<p>Self- funded project<\/p>\n<p><strong>Acknowledgement<\/strong><\/p>\n<p>We sincerely thank the head of the department Microbiology, Dr. S. Gomathi, for making the data available to us.<\/p>\n<p><strong>References<\/strong><\/p>\n<ol>\n<li>Taneja N, Chatterjee SS, Singh M, Singh S, Sharma M. Pediatric urinary tract infections in a tertiary care center from north India. <em>Indian J Med Res<\/em> 2010;131:101-05<\/li>\n<li>Elder JS. urinary tract infection. In: Kliegman, et al. Nelson text book of Pediatrics.19 ed. <em>Philadelphia, Saunders.<\/em> 2011 Pp: 1829-34<\/li>\n<li>Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; twentieth informational supplement. 2010;30(1): M100-S20.<\/li>\n<li>Fatemeh A, Houman H, Masumeh S, Zahra A, Maryam RN, Morteza FK. Aetiologies and Antibiotic Resistance Patterns in Infants With urinary tract Infections Hospitalized in Children Medical Center. <em>Iranian J Neonatology.<\/em> 2013;4(2):21-25.<\/li>\n<li>Akram M, Shahid M, Khan Au. Aetiology and antibiotic resistance patterns of community- acquired urinary tract infection in JNMC Hospital Aligarh. India.<em> AnnClinMicrobiolAntimicrob.<\/em> 2007;6:4.<\/li>\n<li>Sharma A, Shrestha S, upadhyay S, Rijal P. Clinical and bacteriological profile of urinary tract infection in children at Nepal Medical College teaching Hospital. <em>Nepal Med Coll J.<\/em> 2011;13(1):24-26.<\/li>\n<li>Guangying Y, Xueyin Z, Anrong L. Development of a novel test identifying extended-spectrum beta lactamase producing strains relative to resistant plasmids. Chin J <em>Microecol<\/em> 2002;14:89\u201390<\/li>\n<li>Gupta, Kalpana, et al. &#8220;International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases.&#8221;\u00a0<em>Clinical infectious diseases<\/em>\u00a052.5 (2011): e103-e120.<\/li>\n<li>Livermore DM, Warner M, Mushtaq S, Doumith M, Zhang J, Woodford N. What remains against carbapenemresistantEnterobacteriaceae? Evaluation of chloramphenicol, ciprofloxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin and tigecycline. <em>Int J Antimicrob Agents.<\/em> 2011 Mar 21.<\/li>\n<li>Falagas ME, Kastoris AC, Kapaskelis AM, Karageorgopoulos DE. Fosfomycin for the treatment of multidrug-resistant, including extended-spectrum beta-lactamase producing, Enterobacteriaceae infections: a systematic review<em>. Lancet Infect Dis<\/em>. 2010;10:43-50.<\/li>\n<li>Kaltenis P. Cycloserine as a urinary tract antiseptic. 1986;18:125-130.<\/li>\n<li>H. Bauer, G.S. Ble\u00dfmann, D.B. Pitrow, V.W. Rahlfs.\u00a0Prevention of recurrent urinary tract infections with immunoactive E. coli fractions.\u00a0<em>Eur J Obstet Gyn<\/em>. 1999;86:33<\/li>\n<li>G. Riedasch, K. M\u00f6hring.\u00a0ImmunisierungstherapierezidivierenderHarnwegsinfekte der Frau.<em>Therapiewoche<\/em><em>.<\/em> 1986;6:896-900<\/li>\n<li>Lin AE, Beasley FC, Olson J, Keller N, Shalwitz RA, Hannan TJ, et al. (2015) Role of Hypoxia Inducible Factor-1\u03b1 (HIF-1\u03b1) in Innate Defense against Uropathogenic<em>Escherichia coli<\/em>\u00a0Infection. <em>PLoSPathog<\/em> 11(4): e1004818.<\/li>\n<li>Beerepoot MA, terRiet G, Nys S, et al. Lactobacilli vs antibiotics to prevent urinary tract infections: a randomized, double-blind, noninferiority trial in postmenopausal women. <em>Arch Intern Med <\/em>2012;172:704\u201312<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"<p>Introduction Urinary tract infection (UTI) is one of the most  [&#8230;]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[30],"tags":[],"class_list":["post-6805","post","type-post","status-publish","format-standard","hentry","category-vol9no1"],"_links":{"self":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/6805","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/comments?post=6805"}],"version-history":[{"count":4,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/6805\/revisions"}],"predecessor-version":[{"id":7094,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/6805\/revisions\/7094"}],"wp:attachment":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/media?parent=6805"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/categories?post=6805"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/tags?post=6805"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}