Typhoid Fever, also described as an enteric fever, is a serious systemic disorder caused by Salmonella Typhi, primarily caused by the utilization of contaminated food or water, and also poses a serious public health concern, particularly in populations living in regions of poor sanitation and hygienic conditions [29, 30].

Typhoid fever is more prevalent in Africa, Latin America, Asia, India, Southeast Asia, South-Central, and Pakistan, although the disease presents the highest mortality and/or morbidity rates around the globe [31, 32]. Disease progression is particularly associated with ladder-type fever (slowly increasing over a few days), together with gastrointestinal symptoms, leading to serious complications, including intestinal perforation and/or bleeding if kept untreated [33, 34]. Commonly used diagnostic tests include analysis of blood, urine, or stool samples and/or serological investigations, such as the Widal test and the Typhidot [35].

Effective treatment relies particularly on antibiotics tailored to regional resistance patterns, including fluoroquinolones, cephalosporins, and macrolides, together with targeted therapeutics and preventive interventions. Preventive strategies are critical and focused on improved sanitation, quality of drinking water, food safety practices, and vaccination/immunization, particularly in individuals of high-risk localities/travelers [36-38]. The emergence of antibiotic-resistant strains highlights the ongoing need for robust public health strategies and international disease surveillance.

UTI is a bacterial infection most commonly caused by Gram-negative bacteria, notably E. coli, Klebsiella pneumoniae, and Proteus mirabilis, and affects any part of the urinary system. The most common symptoms typically include dysuria, urgency to urinate, burning sensation during urination, frequent urination, hematuria, pelvic pain, foul-smelling urine, and sometimes fever and chills in severe cases [39, 40]. In upper UTIs, fever, flank pain, nausea, and vomiting are common. Older adults may exhibit atypical symptoms such as confusion [41, 42]. UTIs are among the most common infections, particularly in women. Approximately 50–70% of women will experience at least one UTI in their lifetime, and up to 30% may develop recurrent infections [43, 14, 44]. Young, sexually active, and postmenopausal women are especially at risk of developing the infection [45, 46].

Diagnostic tools include Urine culture (gold standard), Blood tests, imaging, and cystoscopy for recurrent/ complicated cases [44, 47]. Treatment includes antibiotics (Nitrofurantoin, Trimethoprim-sulfamethoxazole, Fosfomycin, cephalosporins, fluoroquinolones, ciprofloxacin) and pain killers (paracetamol or ibuprofen) [48, 49].

Pneumonia is a potentially life-threatening disorder affecting either one lung or both lungs, leading to fluid or pus accumulation in the air sacs (alveoli). Its severity varies depending on its causative pathogen, age factor, and underlying health status. Globally, pneumonia ranks as the third leading cause of death and is the foremost fatal communicable disorder, responsible for over 3 million annual deaths [50]. It is particularly deadly among children under five years of age, particularly in developing countries, including Pakistan, where the incidence rate of acute respiratory infections (ARIs) is comparatively high [49]. Numerous types of pneumonia, including aspiration pneumonia, CAP (community-acquired pneumonia), HAP (Hospital-acquired pneumonia), and VAP (ventilator-associated pneumonia), and aspiration pneumonia have been reported [51]. Numerous pathogenic microorganisms are accountable for pneumonia, including bacteria (specifically Streptococcus pneumoniae), fungi, viruses such as influenza, and atypical microbes, including Mycoplasma pneumoniae [52, 53].

Infants, the aged people, smokers, and individuals with compromised immune systems, particularly corresponding to chronic illness history in the past, are considered to be the high-risk subjects.

Disease transmission particularly occurs from the inhalation of airborne droplets, interaction with the contaminated surfaces, and/or aspiration of elements into the lungs [52, 54]. Pathological penetration mainly corresponds to the disruption of the local immune system, including macrophage stimulation, cytokine release, and alveolar inflammation. Cough, fever, chest pain, and dysnea are the most commonly reported symptoms; however, they sometimes lead to more severe complications, like altered mental status, cyanosis, and respiratory distress [4, 55]. Chest x-ray, CBC, and pulse oximetry are the most commonly employed diagnostic tools, whereas vaccination (e.g., pneumococcal and influenza vaccines), amoxicillin, azithromycin, cephalosporins, and fluoroquinolones are based on antibiotic treatment, and preventive measures like smoking cessation and immune health maintenance, together with oxygen therapy, are the most frequently used tactics for pneumonia management. Chronic phases may result in severe complications, including bacteremia, pleural effusion, and respiratory failure with ultimate requirement for immediate clinical intervention and hospitalization [56-58]. Robust immunization patterns and improved patient care systems are the key factors responsible for reduced morbidity and mortality rates around the globe. Keeping in view the reported biological and sociocultural variations impacting disease susceptibility, progression, and therapeutic outcomes among individuals, the current study also focused on sex-disaggregated analysis following SAGER guidelines (Sex and Gender Equity in Research). Biological variability and gender dependent factors like hygienic conditions, occupational environment, and health-seeking behaviors greatly impact the disease progression and ultimate therapeutic outcomes; therefore, sex dependent evaluation of pharmaceutical assessment is necessary to enhance the individualized treatment tactics and related public health interventions.

The current retrospective observational study evaluated 300 confirmed cases of typhoid, pneumonia, and urinary tract infections (UTI) at JIH and DHQ, Abbottabad, for a duration of 1 year, i.e., from October 2023 to October 2024. Data was collected using appropriately designed case profile records of individuals admitted to the medical ward of the aforementioned hospitals. The data collection form was established and authenticated for any corrections after being analyzed by 3 experts (one physician and two pharmacists holding PHD in specific fields) with consequent data collection. The study pattern was adopted in accordance with the previously reported one, with minute modifications [59]. Biological classification of patients (i.e., male/female patients) was recorded in the hospital together with consideration of gender associated determinants, including lifestyle, occupational practices, and hygienic conditions, which were considered during interpretation of the findings. Furthermore, male and female patients were separately analyzed to assess the gender-based variabilities and therapeutic outcomes. the data analysis

The following inclusion criteria were used.

I. Clinical profile of medical ward patients with appropriate diagnoses of typhoid, pneumonia, or UTI.

II. Patients of any age group, including both male and female genders

Includes all treatment regimens, including all the prescribed drugs (both regular and on-demand) from admission till discharge, and any other supplements if prescribed.

III. All the patients included in the study were incorporated after signing written informed consent from the patients, together with the provision of the study protocols [60, 61].

The current study excluded individuals with incomplete case histories and patients with whom confirmation of not suffering from typhoid, pneumonia, or UTI after diagnosis. Furthermore, candidates who refused to participate at any stage of the study or those who died during data collection, diagnosis, or therapy process, or during their hospital stay were also excluded from the study [62, 63].

Data was collected from 375 patients, with 125 case histories for each disease state, i.e., typhoid, pneumonia, and UTI. Among them, 75 case histories (20 case histories of typhoid, 30 case histories of pneumonia, and 25 UTI case histories) were excluded based on inadequate demographic information, incomplete diagnostic test reports/results, insufficient drug prescribed/previously used information, leaving 300 complete cases for study [64].

The data was generated and analyzed from the selected cases for frequency, percentage distribution, and statistical analysis. The major analysis parameters encountered are included.

All the data related to the study was collected manually on printed copies of the SOAP form and might be provided on demand.

I. Demographic Investigation including

II. Clinical Investigation including

Pharmacotherapeutic analysis involved a mixed subjective objective assessment plan (SOAP) format used for data compilation and case assessment with respect to the aforementioned data variables. Subjective data was comprised of patient symptoms, observations, or other related information, whereas physical examinations encompassed the primary source of objective information [66]. Objective information included diagnostic test results such as serum drug concentration, ultrasonography, echocardiogram, biochemical testing, etc. [63, 67]. The standard template was designed by a researcher after following the guidelines provided by the research supervisor to encompass both subjective (S) and objective (O) information for each (Supplementary file).

The study adhered well to the SAGER guidelines. Sex-disaggregated data were analyzed and reported accordingly. Similarly, sex related biological variations were also considered during the study design, analysis, and interpretation. Gender-associated determinants were discussed where applicable.

Based on the mode of admission of patients within the hospitals, the patients were divided into two groups: Group 1, representing patients who visited the outpatient department (OPD), and Group 2, including patients admitted to the Emergency unit (Table 4). Based on the mode of patient’s admission in the aforementioned hospital units, the visit of UTI & pneumonia patients was superior in OPD as compared to emergency units, while the typhoid patient indicated an equal ratio of visits to both sections.

According to the results (Table 5) of patients suffering from typhoid fever, about 61.9% patients were treated with the parenteral (injectable & infusion) route of drug administration, while 38.1% patients were treated with the oral route of drug administration, including 23.8% patients treated with tablets, 11.1% being treated with syrups, and 3.2% being treated using the capsule dosage form.

Accordingly, in the case of patients suffering from UTIs, about 50.3% were treated with the parenteral route of drug administration, including 32.35% patients being treated with injection and 17.95% being treated with infusion. Similarly, 48.52% of individuals were treated with the oral route of drug administration, including 32.35% patients being effectively managed using tablets, followed by 8.82% cases being treated using syrup, while 4.41% were treated with capsule dosage form, and 2.94% with sachets, respectively. In case of UTIs, about 1.47% cases were also prescribed topical dosage form, i.e., creams (Table 5).

Furthermore, in case of findings obtained from the results of pneumonia patients, approximately 54.54% patients were treated with oral dosage forms, including tablets (42.42%), syrups (9.09%), and capsules (3.03%), followed by 38.42% patients being treated with the parenteral route, including 31.82% injection and 6.06% infusion dosage form. Moreover, 7.58% pneumonia patients were also managed using the nasal route of drug administration, i.e., Nebulizer (Table 5).

According to the findings, medication from numerous classes was prescribed for patients suffering from typhoid fever, including Antibiotics, Anti-malarial, Antiemetic, Analgesic/anti-pyretic drugs, proton pump inhibitors, and supplemental nutritional medicaments being administered via parenteral route (Table 6).

Similarly, management of UTI also included medication from numerous classes depending upon the patient’s signs/symptoms and included Antibiotics, Anti-malarial, Antispasmodics, Analgesic/anti-pyretic drugs, Antihypertensive, Laxatives, Protein pump inhibitors, and supplemental medications being administered via oral and parenteral route (Table 7).

Likewise, the medications prescribed for the management of pneumonia included medications from different classes depending upon the patient’s sign/symptoms, and included Antibiotics, Anti-asthmatic, Anti-allergic, Antispasmodics, Analgesic/anti-pyretic drugs, Corticosteroids, Leukotriene modifiers, Laxatives, Oral anti-diabetic drugs, Anti-platelet agent, Proton Pump Inhibitors, and supplemental medications being administered via oral and parenteral route (Table 8).

Concomitant administration of numerous medications indicated minor to moderate level interactions encountered among medications of numerous therapeutic classes, including co-administration of a) Ondansetron, Azithromycin, and Metronidazole with Artemether/ Lumefantrine, b) Omeprazole with Ciprofloxacin, Amoxicillin with Aspirin, Diphenhydramine with Ipratropium bromide, Diphenhydramine with Tamsulosin, and Dexamethasone with Levofloxacin, respectively (Table 9). Upon therapeutic analysis of the included cases' profiles suffering from Typhoid fever, UTI, or pneumonia, the interactions noticed along with their possible consequences and management have been shown in Table 9. It has been observed that all the interactions were easily manageable except the concomitant administration of Antimalarial drug (Artemether/Lumefantrine) with other medications (antiemetic and antimicrobial/antibiotics), creating serious complications, particularly for patients suffering from cardiac complications. In such cases, critical monitoring of patients via daily ECG record maintenance was strictly recommended, as shown in Table 9.

Almost all the patients suffering from the aforementioned infectious disorders (Typhoid fever, Pneumonia, and UTIs) indicated a positive response towards the provided therapeutic regimen, except for few cases such as 4% individuals suffering from typhoid fever (Case: 25, 37, 61 and 93) indicated no remarkable improvement in their symptomatic conditions upon the given treatment protocols based on which they were suggested subsequent diagnostic tests including diagnostic evaluation for malaria and dengue fever. No mortality cases associated with the current disorder were reported upon analysis. Similarly, for pneumonia patients, approximately 7% individuals presented a weak response to the therapeutic regimen, particularly cases 11, 13, 41, 62, 67, 83, and 95, respectively. Most of these candidates belonged to the age group of 61 to 90 years. Most of the patients who indicated a weak therapeutic case response to the given medications were considered to be associated with age-related immunocompromised conditions, altered pharmacokinetics and renal/hepatic functioning, together with patients suffering from multiple comorbidities such as diabetes mellitus, COPD/Asthma, chronic renal dysfunction, and patients indicating complicated pneumonia associated with pleural effusion, lungs abscess and empyema, respectively. Some of these patients were referred to Ayub Teaching Hospital, Abbottabad, while others were suggested further diagnostic procedures. Furthermore, all the patients suffering from UTIs presented a positive response to the therapeutic regimen, except for 5% individuals (Case 31, 55, 79, 88, 98), representing recurrent/complicated UTIs for which the prescribed therapeutic regimen was changed and also suggested follow up visit following 1 week of therapy, based on consideration that a weak therapeutic response might be associated with antibiotic resistance.

All those patients who died during the treatment procedure or at any stage in the hospital were excluded from the study. Furthermore, no cases were observed to develop life-threatening complications as the majority of patients responded well to the recommended therapy protocols. Though non-improvement cases were not observed, prolonged recovery times were particularly associated with smokers upon comparison with non-smokers (particularly in pneumonia patients), and a slower therapeutic response was observed in patients associated with patients suffering from comorbidities among patients of all three infectious diseases.

Certain cases among all the disease groups included in the current study were associated with certain comorbidities, particularly diabetes mellitus, hypertension, COPD, Asthma, weakened immune system, anemia, obesity, etc.

The patients of Typhoid fever (29%) indicated the following comorbidities: diabetes mellitus (11%), malnutrition (particularly observed cases with age groups of 1-10 and 40-50 years), immunocompromised conditions (7%), gastrointestinal complications (4%), together with some cases presenting poor hygienic conditions (2%), together with utilization of unsafe food/water (2%) and smoking abuse (3%) (Table 10). Similarly, the pneumonia patients (24%) also presented certain comorbidities, like age-related immunocompromised conditions (3%), altered pharmacokinetics, renal or hepatic malfunctioning (3%), diabetes mellitus (4%), COPD/Asthma (4%), Anemia (1%), gastrointestinal reflux disease (GERD) (1%), obesity (3%), and symptoms of complicated pneumonia such as pleural effusion, lung abscess, and empyema (5%), particularly associated with previous or current smoking history. Furthermore, in the case of UTI patients (18%), the following comorbidities have been observed: Diabetes mellitus (3%), hypertension (6%), dehydration (2%), urine burning (1%), incomplete bladder emptying, urinary retention, and recurrent UTIs (6%).