Clinical presentation and outcome of enteric fever in adult patients with cancer: a perspective from Pakistan.

Introduction. Enteric fever is a significant health concern in endemic countries. While extensive research has been conducted to understand its presentation and outcomes in non-cancer patients, limited data exist on its impact on cancer patients. This descriptive study aims to investigate the clinical presentation and outcome in cancer patients. Methodology. This retrospective observational study analysed 90 adult cancer patients from a single centre in Pakistan from January 2017 to December 2022. Inclusion criteria involved documented blood culture infections with Salmonella typhi or paratyphi A, B, or C. We examined clinical presentation, laboratory parameters, antimicrobial resistance, complications, and outcomes. Additionally, we explored the effects of chemotherapy, comorbidities, type of malignancy, and patient age on complications and mortality. Results. Salmonella typhi was the most prevalent organism (72.2 %), followed by Salmonella paratyphi A (22.2 %) and B (5.5 %). Variably-resistant isolates constituted 51.5 %, multi-drug resistant (MDR) isolates accounted for 20 %, extensively drug-resistant (XDR) for 14.4 % and ESBL-producers for 15.5 %, of all enteric fever infections. Enteric fever-associated complications were observed in 21.1 % of cases. Chemotherapy in the preceding month did not affect mortality, nor did age, gender, or malignancy type. However, comorbidities were statistically significant for mortality (p-value 0.03). A total of 8.8 % of patients required ICU care, and the all-cause 30 day mortality rate was 13.3 % Conclusion. Enteric fever remains prevalent in our geographical region. Unlike non-typhoidal Salmonella (NTS), enteric fever does not behave differently in an immunocompromised population, including cancer patients.

Trends in typhoid fever during the COVID-19 pandemic in Pakistan.

INTRODUCTION: Pakistan has been experiencing an extensively drug-resistant (XDR) outbreak of typhoid for some years. We sought to evaluate how the COVID-19 pandemic impacted typhoid epidemiology in Pakistan, from the beginning of the pandemic in 2020 through the end of 2022, and the reduction of COVID-19 cases. METHODOLOGY: We compared national public COVID-19 data with retrospectively obtained patient data of confirmed S. Typhi isolates between January 2019 and December 2022 from Shaukat Khanum Memorial Cancer Hospital and Research Centre and the hospital's extended network of laboratory collection centers across Pakistan. RESULTS: We observed that during the early onset of the COVID-19 pandemic and COVID-19 peaks, typhoid positivity generally decreased. This suggests that restrictions and non-pharmaceutical interventions that limited social interactions and promoted good sanitation and hygiene practices had a positive secondary effect on typhoid. This led to an overall yearly decrease in typhoid positivity between 2019 to 2021. However, the percentage of S. Typhi cases isolated that were ceftriaxone-resistant continued to increase, suggesting the continued dominance of XDR typhoid in Pakistan. In 2022, with the alleviation of pandemic restrictions, we observed increased typhoid positivity and COVID-19 and typhoid positivity started to follow similar trends. CONCLUSIONS: Given the continued presence of COVID-19 along with XDR typhoid in Pakistan, it will be imperative to use differential testing to ensure that the epidemiology of each reported is accurate, the spread of each it contained, and that antibiotics are not misused. The use of approved vaccinations will lessen the burden of both diseases.

Therapeutic efficacy and safety results of 177Lu-PSMA therapy in metastatic castration-resistant prostate cancer patients: first experience of a developing South Asian Country.

OBJECTIVE: Metastatic castration resistant-prostate cancer (mCRPC) is deadly condition that remains incurable despite various therapies. Initial studies have shown promising results with Lutetium-177 prostate-specific membrane antigen ( 177 Lu-PSMA) therapy for advanced prostate cancer. However, most of the published efficacy and safety data is retrospective. The purpose of the study was to prospectively evaluate the therapeutic efficacy and safety results of 177 Lu-PSMA therapy in mCRPC patients after 2 cycles. METHODS: Twenty-five patients of mCRPC, treated with standard care treatment were enrolled for 2 cycles of 177 Lu-PSMA therapy. Prostate-specific antigen (PSA), Eastern Cooperative Oncology Group (ECOG) performance status, Visual Analogue Score (VAS) and Analgesic Quantification Scale (AQS) for efficacy and hemoglobin, total leukocyte, platelets and serum creatinine for toxicity were recorded pre and post-therapy. Paired sample t-test was used for statistical analysis. RESULTS: Treated patients with mean PSA level of 157 ng/ml received mean dose of 6.84 GBq of 177 Lu-PSMA. For PSA, partial response (PR) was seen in 11/25 (44%), stable disease (SD) in 8/25 (32%) and progressive disease (PD) in 6/25 (24%) patients. Grade 1 and 2 hemoglobin toxicity was seen in 5/25 (20%) and 6/25 (24%) patients respectively. No patient developed grade 3 or 4 bone marrow toxicities. Grade 1 and 2 nephrotoxicity was seen in 1 patient each. Statistically significant difference was seen in ECOG, VAS and AQS scores ( P  < 0.001). No significant nephrotoxicity was observed ( P  = 0.558). CONCLUSION: Efficacy and safety of 177 Lu-PSMA therapy after 2 cycles have shown significant PSA response and pain palliation in heavily pretreated mCRPC patients.

Antibiotics Associated With Clostridium difficile Infection.

Introduction Clostridium difficile (C. difficile) is one of the major causes of diarrhea transmitted by the fecal-oral route. C. difficile type BI/NAP1/027 is responsible for the most severe C. difficile infection (CDI). It is a major cause of antibiotic-associated diarrhea followed by Clostridium perfringens, Staphylococcus aureus,and Klebsiella oxytoca. Historically, clindamycin, cephalosporins, penicillins, and fluoroquinolones were related to CDI. We conducted this study to evaluate the antibiotics associated with CDI in recent times. Methods We conducted a retrospective, single-center study over a period of eight years. A total of 58 patients were enrolled in the study. Patients with diarrhea and positive C. difficile toxin in stool were evaluated for antibiotics given, age, presence of malignancy, previous hospital stay for more than three days in the last three months, and any comorbidities. Results Among patients who developed CDI, prior antibiotics for at least four days duration were given in 93% (54/58) of patients. The most common antibiotics associated with C. difficile infection were piperacillin/tazobactam in 77.60% (45/58), meropenem in 27.60% (16/58), vancomycin in 20.70% (12/58), ciprofloxacin in 17.20% (10/58), ceftriaxone in 16% (9/58), and levofloxacin in 14% (8/58) of patients, respectively. Seven percent (7%) of patients with CDI did not receive any prior antibiotics. Solid organ malignancy was present in 67.20% and hematological malignancy in 27.60% of CDI patients. Ninety-eight percent (98%, 57/58) of patients treated with proton pump inhibitors, 93% of patients with a previous hospital stay for more than three days, 24% of patients with neutropenia, 20.1% of patients aged more than 65 years, 14% of patients with diabetes mellitus, and 12% of patients with chronic kidney disease also developed C. difficile infection. Conclusion The antibiotics associated with C. difficile infection are piperacillin/tazobactam, meropenem, vancomycin, ciprofloxacin, ceftriaxone, and levofloxacin. Other risk factors for CDI are proton pump inhibitor use, prior hospital admission, solid organ malignancy, neutropenia, diabetes mellitus (DM), and chronic kidney disease (CKD).

Trends of Vancomycin-Resistant Enterococcus Infections in Cancer Patients.

Objective Vancomycin-resistant Enterococcus (VRE) is an important cause of infection in immunocompromised populations. In Pakistan, very limited data are available regarding Enterococcus infection and its outcomes. We conducted this study to evaluate the trends including risk factors, treatment options, and outcomes of infections due to vancomycin-resistant enterococci in cancer patients in Pakistan. Methods We conducted a retrospective observational study. We extracted data from medical records of our center over a period of seven years. All admitted cancer patients with any vancomycin-resistant Enterococcus positive culture were included. The following parameters were evaluated: age, gender, type of cancer, febrile neutropenia, prior antibiotics, admission, comorbidities, system-wise infections (including bacteremia, catheter-related infection, pneumonia, urinary tract infections, intra-abdominal infection, bone and joint infections, skin and skin structure infections), intensive care unit admission, and 30-day all-cause mortality. Frequencies of infections, mortality, and drug susceptibility were evaluated over the course of seven years. Results Risk factors for enterococcal infection included prior exposure of piperacillin/tazobactam (n=209, 86.7%), meropenem (n=132, 54.8%), vancomycin (n=126, 52.3%), metronidazole (n=67, 27.8%), prior admission for more than 48 hours (n=198, 82.2%), and comorbidities (n=76, 31.5%), with acute kidney injury being most common (n=72, 95%) followed by diabetes mellitus (n=70, 92.1%). Precursor B cell acute lymphoblastic leukemia (pre-B ALL) was the most common malignancy in which infection occurred (n=54, 38.3%). Among patients who developed infection, 46% (n=111) had febrile neutropenia. Enterococcus species caused infection in 61% (n=147) and Enterococcus faecium in 39% (n=94). Bacteremia occurred in 45.2% (n=109) patients followed by urinary tract and intra-abdominal infection; 45.6% (n=110) patients were admitted to ICU, and 30-day all-cause mortality was 44.8% (n=108). Linezolid sensitivity was 100%. The total number of enterococci infections decreased over seven years. Frequency of E. species infection, bacteremia, intra-abdominal, skin-related infections, and recurrent infection also decreased, but the frequency of E. facium infections, ICU admission, and 30-day all-cause mortality was increased. Conclusion VRE infections have become less frequent but more severe in recent years with increase in mortality. Prior use of antibiotics (including piperacillin/tazobactam, vancomycin, carbapenems, and metronidazole), diagnosis of hematological malignancy, febrile neutropenia, diabetes mellitus, and renal failure are the risk factors for VRE infection. Bacteremia was the most common infection with high mortality rate. All strains remain sensitive to linezolid. Patients with these risk factors should be worked up for VRE and can be treated with linezolid empirically.

Probing the effect of Ni, Co and Fe doping concentrations on the antibacterial behaviors of MgO nanoparticles.

The divalent transition metal ions (Ni, Co, and Fe)-doped MgO nanoparticles were synthesized via the sol-gel method. X-ray diffraction showed the MgO pure, single cubic phase of samples at 600 °C. Field emission electron microscope showed the uniform spherical shape of samples. The magnetic behavior of Ni, Co, Fe-doped MgO system were varied with Ni, Co, Fe content (0.00, 0.01, 0.03, 0.05, 0.07). The magnetic nature of pure had changed from paramagnetic to ferromagnetic. The number of oxygen vacancies increases with increasing amounts of dopant ions that lead to an ionic charge imbalance between Ni2+/Co2+/Fe2+ and Mg2+, leading to increase magnetic properties of the samples. The magnetic nature of prepared samples makes them suitable for biomedical applications. A comparative study of the antibacterial activity of nanoparticles against the Gram-negative (E. coli) and Gram-positive bacteria (S. aureus) was performed by disc diffusion, pour plate techniques, and study surface morphology of untreated and treated bacterial cell wall. An investigation of the antibacterial activity of doped MgO nanoparticles reveals that the doped MgO nanoparticles show effective antibacterial activity against the Gram-negative (E. coli) and Gram-positive (S. aureus) bacterium. The minimum inhibitory concentration of the synthesized nanoparticles against microorganisms was recorded with 40 µg/ml, while the maximum inhibitory concentration was observed with 80 µg/ml. At a concentration of 80 µg/ml, the complete growth inhibition of the E. coli was achieved with 7% Co-doped MgO and 7% Fe-doped MgO, while bacterial growth of S. aureus was inhibited by 100% in the presence of 7% Fe-doped MgO. The present work is promising for using nanomaterials as a novel antibiotic instead of the conventional antibiotics for the treatment of infectious diseases which are caused by tested bacteria.

Educational intervention to improve the knowledge of hand hygiene in pediatric residents and nurses.

OBJECTIVES: To assess the improvement in the knowledge of hand hygiene in Pediatric residents and nurses after theoretical and hands-on educational intervention. METHODS: This study was a questionnaire-based cross-sectional survey carried out in the department of Pediatrics, King Edward Medical University/ Mayo hospital Lahore in two weeks period. Total 41 Pediatrics residents and nurses, participated in the study. Initially a pretest questionnaire was given to each participant, followed by an educational intervention: a day's worth of didactic lectures and practical training of practices for infection control. After two weeks, an identical post-test questionnaire was sent to the participants via email. Data were statistically analyzed through SPSS 22. Z test was applied to see the normality of data while paired t test was applied to compare the pretest score with posttest score. RESULTS: Of 41 participants who attended the workshop, 34 participants responded to post-test giving an overall response rate of 83%. Out of 34, there were 27(80%) doctors and 7(20%) nurses, who participated in workshop. Each item of the questionnaire was analyzed, showing that pretest score for questions related to indication for hand washing, minimum timings required for hand rub, and spread of infection from unclean hands was quite low, as compared to post-test score, indicating statistically significant increment (p value 0.000, 0.001and 0.046 respectively). Mean pre-test score for doctors was 3.22 while for nurses, it was 3.14, whereas post-test score was 4.51 and 4.00 for doctors and nurses respectively. Overall, there was statistically significant increase in knowledge after educational intervention. CONCLUSION: There is statistically significant impact of educational intervention on improving the knowledge of Pediatric residents and nurses with respect to hand hygiene practices.

Association of Impaired Fasting Glucose with Hypertension.

OBJECTIVE: To evaluate the association of impaired fasting glucose (IFG) with hypertension in Pakistani population. STUDY DESIGN: A cross-sectional, analytical study. PLACE AND DURATION OF STUDY: Shifa Community Health Centre, Islamabad from December 2016 to July 2017. METHODOLOGY: One hundred and eighty-seven hypertensive patients were included in the study, using consecutive sampling technique. Demographic, anthropometric, and laboratory data of the patients were recorded. Continuous variables were expressed as mean + SD and categorical variables as numbers and percentages. Differences among males/females and between hypertensive patients with normal, impaired fasting glucose and diabetes for risk factors were analysed, using independent sample t-test, ANOVA and chi-square test using SPSS version 24. RESULTS: The mean age of patients was 52.98 +11.22 years. Females were 69.9% and males 30.1%. The total frequency of IFG in patients with hypertension was 42.6% and new onset diabetes 12.5% showing its close association with hypertension. There was no significant difference between males and females for risk factors (age, BMI, blood pressure, total cholesterol, LDL-cholesterol, and HDL-cholesterol) except for more education, smoking, and high triglyceride in males. There was no significant difference among hypertensive patients with normal, impaired fasting glucose and diabetes for risk factors (gender, BMI, blood pressure, total cholesterol, LDL-cholesterol, triglycerides, HDL-cholesterol and family history) except for smoking. CONCLUSION: The significant association of impaired fasting glucose with hypertension necessitates early screening for impaired fasting glucose.

Emergence of Circulating Recombinant Form 56_cpx in Pakistan.

In Pakistan, HIV has converted from outbreak to concentrated epidemic and has also bridged into the low-risk population. The HIV epidemic in Pakistan mainly comprises subtype A. Here, we present the first case and genetic analysis of a circulating recombinant form 56_cpx in a Pakistani HIV-infected patient. Genetic analysis of the sequence indicated that Pakistani 56_cpx sequence had more drug resistance mutation than the other 56_cpx sequences available in the database.

Bacteraemia caused by Escherichia coli in cancer patients at a specialist center in Pakistan.

OBJECTIVE: To analyse the antimicrobial susceptibility patterns of Escherichia coli bacteraemia among cancer patients, and to assess the risk factors and outcomes of multidrug-resistant Escherichia coli bacteraemia. METHODS: The retrospective study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, and comprised medical records of patients with Escherichia coli bacteraemia presenting between December 2012 and November 2013. Multivariable logistic regression analyses were used to determine the factors associated with the development and 30-day mortality of multidrug-resistant Escherichia coli bacteraemia. RESULTS: Out of 1603 episodes of bacteraemia, 227(35.6%) were caused by E.coli, of which 98(43.2%) were multidrug-resistant. In multivariable analysis, age less than 18 years (adjusted odds ratio 3.92; 95% confidence interval 1.43-10.68), presence of central venous catheter (adjusted odds ratio 2.12; 95% confidence interval 1.04-4.33) and exposure to piperacillin/tazobactam within 90 days prior to infection (adjusted odds ratio 2.37; 95% confidence interval 1.15-4.86) were identified as independent risk factors for acquisition of multidrug-resistant Escherichia coli bacteraemia. The overall 30 day mortality rate was 35.2% (80/227). Risk factors for mortality were intensive care unit admission (adjusted odds ratio 3.95; 95% confidence interval 1.79-8.71) and profound neutropenia (adjusted odds ratio 4.03; 95% confidence interval 1.55-10.49). CONCLUSIONS: Bloodstream infections with multidrug-resistant Escherichia coli were common in cancer patients. However it was not a predictor of mortality.