{'fraction_non_alphanumeric': 0.02921087051300683, 'fraction_numerical': 0.018456619677372475, 'mean_word_length': 5.5418250950570345, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 1, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Recent Antimicrobial Susceptibility Patterns of Salmonella Isolates in A Tertiay Care Hospital Lahore

Objective: To determine the recent antimicrobial susceptibility patterns of salmonella isolates (typhi and paratyphi) in a tertiary care hospital of Lahore. Methods: It is cross sectional retrospective study conducted out in King Edward Medical University(Pathology deptt)/Mayo Hospital Lahore.The study period is six months from May 2019 to October 2019(Peak months of Typhoid fever).During this six months study period, total of 4284 samples for blood culture were received that were inoculated on the macConkey and blood agar plates.The growths obtained were then processed through biochemical profiling and analytical profile index(API).The Kirby Bauer technique was used for antibiotic susceptibility testing and reporting was done on the basis of clinical laboratory standard institute(CLSI). Results: During these six months, total 4284 blood samples were inoculated, out of which 433 growths were obtained. There were 84 strains of salmonella typhi isolated. Sensitivity pattern of different antibiotics showed that Azithromycin was sensitive to 70 (83.3%) isolates, imipenem in 72 (85.7%), ciprofloxacin to 56 (66.7%), gentamycin to 48 (57.1%), ceftriaxone to 45 (53.6%), cefepime to 20 (23.8%), chloramphenicol to 12 (14.3%) while ampicillin was least sensitive i.e. 8 (9.5%) isolates. There were 24 MDR(multidrug resistant) and 12 were XDR(extensive drug resistant) strains. We also found out that resistance to azithromycin drug is also emerging as 70 out of 84 strains were sensitive while remaining 14 were resistant. Conclusion: According to recent antibiotic susceptibility against salmonella typhi, the most sensitive drugs are Carbapenems (imipenem or meropenem) these days. Second sensitive antibiotic is azithromycin.


Introduction
Typhoid fever is an acute and sometimes life-threatening infectious disease. It remains an enormous public health threat in many developing countries (including Pakistan) due to inadequate access to safe water, poor sanitation system and inappropriate use of 1 antimicro-bial drugs. An estimated 21 million infections and above 1.6 lac deaths occur by typhoid fever worldwide each year. It is prevalent in Pakistan, 2 that mostly affects children and teenagers. Salmonella typhi is responsible for almost 30% of community acquired bacterial bloodstream infections in Asian population, whilst salmonella paratyphi A is an emerging pathogen that causes upto 35% of all enteric fever episodes. Notably, paratyphoid fever has 3 almost common features as that of typhoid fever. Salmonella enterica (typhi and paratyphi isolates) is a facultative intracellular and human restricted pathogen, predominantly transmitted by feco-oral route. Salmonella typhi is a gram negative, rod shaped, flagellated bacterium. It has a polysaccharide capsule that increases its virulence by inhibiting phagocytosis. 4 It is H2S producing motile organism. Blood culture, urine and stool examination, serology and PCR (polymerase chain reaction) is available for diagnosing typhoid fever. Out of all these tests, blood 5 culture and PCR is considered as gold standard. The WHO currently recommends imipenem, ampicillin, sulphamethoxazole-trimethoprim, flouroquinolones, 3rd generation cephalosporins (ceftriaxone, cefixime) and azithromycin(AZM) for the treatment of typhoid 6 fever. Multiple drug resistant (MDR) typhoid fever is defined as resistance against three first line drugs including ampicillin, chloramphenicol and sulphamethoxazole-trimethoprim. In Pakistan it was reported to be 40%. After that flouroquinolones overtake as first line therapy but in early 2000, emerging resistance against flouroquinolones was increasingly being reported. In these circumstances, third generation cephalosporins become the treatment of choice for 8 typhoid febrile illness in Pakistan. Currently sporadic cases of extensive drug resistant (XDR) typhoid are frequently being reported. XDR salmonella typhi is resistant to ampicillin, chloramphenicol, sulphamethoxazole-trimethoprim, flouroquinolones and ceftriaxone. For these cases, azithromycin and carbapenems are prescribed in XDR typhoid fevers. Recently it also has lost credibility 7,9 due to emergence of resistance because of its overuse. We planned to conduct this study in order emphasize the alternating trends of salmonella typhi antibiotic susceptibility to antibiotics in past few years in Pakistan, As XDR salmonella typhi infections is an alarming situation that is causing increase in mortalities.

Methods
It was a retrospective cross sectional study conducted at department of pathology, King Edward Medical University Lahore for six months i.e. May 2019 to October 2019.After ethical approval, 4284 samples of blood cultures received from the inpatient and outpatient departments of Mayo Hospital Lahore. All the blood cultures recieved were inoculated on two plates i.e blood and macConkey agar. The growth obtained was then further processed through biochemical profiling and analytical profile index (API) 20E. The Kirby Bauer technique was used for antibiotic susceptibility testing and reporting was done on the basis of Clinical Laboratory Standard Institute (CLSI) 2019.

Discussion
Esculapio -Volume 17, Issue 01 2021 -www.esculapio.pk -46 The findings of this study clearly shows that MDR and XDR salmonella infections are emerging fastly. Most of the strains were sensitive to carbapenems and secondly to azithromycin. So, meropenem/imipenem and azithromycin are good choices of drug treatment for typhoid fever at present. There was peak of MDR salmonella typhi epidemic in south and southeast Asia in the early 1990s. In these cases flouroquinolones were recommended. After mutations of strains of salmonella typhi, flouroquinolones resistance developed that led to usage of parenteral ceftriaxone, that required hospitalization. Whereas antimicrobial resistance to these drugs is also increasing, such as recent emergence of XDR salmo- enterobactereicae is also a serious issue.
Small sample size, short duration study (6 months), antimicrobial pre-treatment and decreased sensitivity of blood cultures as compared to PCR are the main limitations of our study. Others include lack of minimum inhibitory concentration (MIC) and extended spectrum beta lactamases (ESBL) testing for different antibiotics.

Conclusion
It was concluded that carbapenems (meropenem or imipenem) and azithromycin are drugs of choice for XDR salmonella typhi infections now-a-days & antibiotic stewardship is required in order to prevent the prevailing resistance to different antibiotics.
In the background of rising MDR and XDR infections, healthy policy making, improved healthcare and institutional facilities and effective antibiotic stewardship is the need of hour to combat this problem.