Background: There are concerns with inappropriate prescribing of antibiotics in hospitals especially broad spectrum in Pakistan and the subsequent impact on antimicrobial resistance rates. One recognized way to reduce inappropriate prescribing is for empiric therapy to be adjusted according to the result of culture sensitivity reports. Objective: Using culture sensitivity reports to optimize antibiotic prescribing in a teaching hospital in Pakistan. Methods: A retrospective observational study was undertaken in Ghurki Trust Teaching Hospital. A total of 465 positive cultures were taken from patients during the study period (May 2018 and December 2018). The results of pathogen identification and susceptibility testing from patient-infected sites were assessed. Additional data was collected from the patient\'s medical file. This included demographic data, sample type, causative microbe, antimicrobial treatment, and whether empiric or definitive treatment as well as medicine costs. Antimicrobial data was assessed using World Health Organization\'s Defined Daily Dose methodology. Results: A total of 497 isolates were detected from the 465 patient samples as 32 patients had polymicrobes, which included 309 g-negative rods and 188 g-positive cocci. Out of 497 isolates, the most common Gram-positive pathogen isolated was Staphylococcus aureus (Methicillin-sensitive Staphylococcus aureus) (125) (25.1%) and the most common Gram-negative pathogen was Escherichia coli (140) (28.1%). Most of the gram-negative isolates were found to be resistant to ampicillin and co-amoxiclav. Most of the Acinetobacter baumannii isolates were resistant to carbapenems. Gram-positive bacteria showed the maximum sensitivity to linezolid and vancomycin. The most widely used antibiotics for empiric therapy were cefoperazone plus sulbactam, ceftriaxone, amikacin, vancomycin, and metronidazole whereas high use of linezolid, clindamycin, meropenem, and piperacillin + tazobactam was seen in definitive treatment. Empiric therapy was adjusted in 220 (71.1%) cases of Gram-negative infections and 134 (71.2%) cases of Gram-positive infections. Compared with empiric therapy, there was a 13.8% reduction in the number of antibiotics in definitive treatment. The average cost of antibiotics in definitive treatment was less than seen with empiric treatment (8.2%) and the length of hospitalization also decreased. Conclusions: Culture sensitivity reports helped reduced antibiotic utilization and costs as well as helped select the most appropriate treatment. We also found an urgent need for implementing antimicrobial stewardship programs in hospitals and the development of hospital antibiotic guidelines to reduce unnecessary prescribing of broad-spectrum antibiotics.

UNASSIGNED: Antibiotic de-escalation is a key element of antimicrobial stewardship programs that restrict the spread and emergence of resistance. This study was performed to evaluate the impact of positive culture sensitivity reports of E. coli or Methicillin sensitive Staphylococcus aureus (MSSA) on de-escalation of antibiotic therapy.
UNASSIGNED: This prospective observational study was performed on 256 infected patients. The samples were obtained principally from the pus of infected sites for the identification of pathogens and culture-sensitivity testing. The data were collected from patient medical files, which included their demographic data, sample type, causative microbe and antimicrobial treatment as empiric or definitive treatment based on cultures. Data were analyzed using SPSS.
UNASSIGNED: Of 256 isolated microbes, 138 (53.9%) were MSSA and 118 were E. coli (46.1%). MSSA showed 100% sensitivity to cefoxitin, oxacillin, vancomycin, fosfomycin, colistin and more than 90% to linezolid (95.3%), tigecycline (93.1%), chloramphenicol (92.2%) and amikacin (90.2%). E. coli showed 100% sensitivity to only fosfomycin and more than 90% to colistin (96.7%), polymyxin-B (95.1%) and tigecycline (92.9%). The high use of cefoperazone+sulbactam (151), amikacin (149), ceftriaxone (33), metronidazole (30) and piperacillin + tazobactam (22) was seen with empiric prescribing. Following susceptibility testing, the most common antibiotics prescribed for E. coli were meropenem IV (34), amikacin (34), ciprofloxacin (29) and cefoperazone+sulbactam (25). For MSSA cases, linezolid (48), clindamycin (30), cefoperazone+ sulbactam IV (16) and amikacin (15) was used commonly. Overall, there was 23% reduction in antibiotic use in case of E. coli and 43% reduction in MSSA cases.
UNASSIGNED: Culture sensitivity reports helped in the de-escalation of antimicrobial therapy, reducing the prescribing of especially broad-spectrum antibiotics. Consequently, it is recommended that local hospital guidelines be developed based on local antimicrobial susceptibility patterns while preventing the unnecessary use of broad-spectrum antibiotics for empiric treatment.

Congenital athymia can present with severe T cell lymphopenia (TCL) in the newborn period, which can be detected by decreased T cell receptor excision circles (TRECs) on newborn screening (NBS). The most common thymic stromal defect causing selective TCL is 22q11.2 deletion syndrome (22q11.2DS). T-box transcription factor 1 (TBX1), present on chromosome 22, is responsible for thymic epithelial development. Single variants in TBX1 causing haploinsufficiency cause a clinical syndrome that mimics 22q11.2DS. Definitive therapy for congenital athymia is allogeneic thymic transplantation. However, universal availability of such therapy is limited. We present a patient with early diagnosis of congenital athymia due to TBX1 haploinsufficiency. While evaluating for thymic transplantation, she developed Omenn Syndrome (OS) and life-threatening adenoviremia. Despite treatment with anti-virals and cytotoxic T lymphocytes (CTLs), life threatening adenoviremia persisted. Given the imminent need for rapid establishment of T cell immunity and viral clearance, the patient underwent an unmanipulated matched sibling donor (MSD) hematopoietic cell transplant (HCT), ultimately achieving post-thymic donor-derived engraftment, viral clearance, and immune reconstitution. This case illustrates that because of the slower immune recovery that occurs following thymus transplantation and the restricted availability of thymus transplantation globally, clinicians may consider CTL therapy and HCT to treat congenital athymia patients with severe infections.

Cervical cancer remains a major health challenge in the United States (US), especially among the low socioeconomic and African American populations. The demographics of Mississippi constitute a relatively high percentage of this high-risk population. External beam radiation therapy (EBRT) combined with concurrent chemotherapy and followed by brachytherapy is the gold standard of treatment for stage IB3 through IVA cervical cancer. Arguably, brachytherapy is the most important component of this treatment process. Patterns of Care studies (PCS) and other more recent studies have shown that brachytherapy cannot be omitted or replaced by conventional or image-guided EBRT. The last decade has witnessed the expanding use of image-guided brachytherapy (IGBT). Studies have established the superiority of IGBT over point-based brachytherapy. MRI is associated with superior soft tissue definition compared with CT and is emerging as the new standard of care. The Gynaecological Groupe Européen de Curiethérapie and the European Society for Radiotherapy and Oncology [(GYN) GEC-ESTRO] have recommended that the dose be prescribed to the high-risk clinical target volume (HR-CTV). This volume includes residual tumor present at the time of brachytherapy, the cervix, and any gray areas seen on the scan. The (GYN) GEC-ESTRO has shown that a dose of >8500 cGy delivered in <50 days results in an approximate 10% increase in pelvic control (PC), disease-specific survival, and overall survival (OS) compared to historical controls. The normal tissue toxicity is comparable or better than historical controls as well. This dose, while maintaining normal tissue constraints, may only be achievable with a hybrid intracavitary/interstitial (IC/IS) needle device guided by MRI-based targeting.  The University of Mississippi Medical Center (UMMC) has initiated an MRI-based cervical brachytherapy program and has treated 18 patients to date; our experience confirms the above findings. In this report, we propose that MRI guidance is necessary and a hybrid IC/IS needle device is required to achieve adequate dose coverages.