Prospective Evaluation of Cephalosporin Prescribing and Guideline Adherence in Adult Inpatients at a Tertiary Care Hospital in South India

Abstract

Objective:

This study aimed to assess cephalosporin prescribing patterns, clinical appropriateness, susceptibility and resistance profiles, potential drug–drug interactions, and de-escalation practices in the management of infectious diseases.

Methods:

This prospective observational study was conducted over 6 months (May–October 2024) at a tertiary care hospital in South India. A total of 288 adult patients (>18 years) who received at least one cephalosporin prescription were included. Relevant demographic, clinical, and prescription data were collected from the patient case records. The appropriateness of antimicrobial therapy was evaluated according to the Indian Council of Medical Research antimicrobial stewardship guidelines. Data were entered into Microsoft Excel and analyzed using IBM SPSS Statistics version 20.0.

Findings:

Among the 288 patients, 383 cephalosporin prescriptions were documented. Culture testing was performed in 63% (n = 181) of cases; however, only 13.9% (n = 40) showed positive microbial growth. Escherichia coli was the most frequently isolated organism, accounting for 30% (n = 12) of culture-positive cases. Guideline-based evaluation revealed that 32.4% of cephalosporin prescriptions were inappropriate, indicating a significant deviation from evidence-based practice.

Conclusion:

Third-generation cephalosporins were predominantly prescribed in the study population. Although cephalosporins remain important and accessible therapeutic agents, inappropriate and empirical prescribing practices contribute to the rising antimicrobial resistance. Rational use guided by culture sensitivity results and antimicrobial stewardship principles is essential to preserve their clinical efficacy and limit further resistance.

INTRODUCTION

Cephalosporins are widely used empirical antibiotics that have evolved through five generations and serve as the essential components of antimicrobial therapy owing to their broad spectrum of activity and favorable safety profile.[1,2] Their extensive clinical applications range from the management of community-acquired infections to their use as prophylactic agents in surgical procedures.[3,4] Despite their proven efficacy, inappropriate prescribing and inadequate antimicrobial stewardship have contributed to the rising antimicrobial resistance, complicating therapeutic outcomes.[5,6] Recent reports have emphasized the importance of drug utilization evaluation in monitoring prescribing trends, resistance patterns, and compliance with treatment guidelines.[7,8] This study aimed to evaluate the current clinical practices related to cephalosporin use, including their spectrum of activity, clinical indications, resistance patterns, and adherence to best-practice guidelines. Such evidence is essential to promote the rational use of cephalosporins and to sustain their long-term effectiveness in clinical practice.

METHODS

A prospective and observational study was conducted over 6 months, from May 2024 to October 2024, in the medical ward of a tertiary care hospital in South India, encompassing the departments of General Medicine, Pulmonology, Gastroenterology, Oncology, and Gynecology. A total of 288 patients were enrolled, and the study was approved by the Institutional Ethics Committee (Ref. No: 24/BC-025/IEC/2024).

Participants included inpatients aged >18 years of either sex who were diagnosed with infectious diseases and prescribed cephalosporins. Patients aged <18 years, outpatients, patients prescribed cephalosporins for surgical prophylaxis, critical care patients, and individuals unwilling to participate were excluded from the study.

The sample size of 288 was calculated based on a 25% prevalence[9] of cephalosporin use, with a 5% precision, 95% confidence interval, and a 5% level of significance, using the formula: Z (1− α/2)² × P (1 − P)/d², where Z (1− α/2) = 1.96. A consecutive sampling method was employed to ensure systematic enrolment of eligible participants. No randomization was performed, and no additional selection criteria were applied beyond the predefined eligibility parameters, ensuring an unbiased case capture and accurate representation of the real-world prescribing patterns. All eligible patients were included until the target sample size was achieved. After obtaining ethical approval, relevant data were extracted from the patients’ medical records using a structured data collection form that captured demographic details, medical and medication history, diagnosis, laboratory parameters (hemoglobin, white blood cell, erythrocyte sedimentation rate, differential count, and C-reactive protein), radiological findings, and culture sensitivity results. The clinical samples for microbiological testing were collected when culture testing was requested, which occurred after the initiation of empirical antibiotic therapy in most cases. Antimicrobial susceptibility testing was performed by the hospital microbiology laboratory using the microbroth dilution method in accordance with the CLSI guidelines.

Cephalosporin prescription characteristics, including dose, formulation, frequency, route of administration, and documented susceptibility/resistance profiles, were systematically recorded. Prescriptions were categorized as empirical or definitive and assessed for monotherapy, dual therapy, or triple antibiotic regimens. The appropriateness of therapy was evaluated according to the Indian Council of Medical Research (ICMR) guidelines and institutional antibiotic policy, based on indication, dose, route, frequency, and duration, any deviation was categorized as inappropriate. Inappropriate prescribing included incorrect indication, inappropriate drug selection, inaccurate dose or frequency, unsuitable duration of therapy, lack of dose adjustment in renal impairment, use in nonbacterial conditions, and failure to modify therapy based on culture and sensitivity results when available.

Bacteriological profiles and susceptibility patterns were reviewed, and potential drug interactions were identified using the Lexicomp software. Patients were monitored daily until discharge, with ongoing assessment of clinical status, culture results, laboratory markers, treatment modifications, adverse events, and possible drug interactions. Data entry was completed using Microsoft Excel, and statistical analyses were performed using IBM SPSS Statistics Version 20 (IBM Corporation, Armonk, New York, USA). Findings were summarized as frequencies and percentages, and the association between empirical versus definitive therapy and culture positivity was evaluated using the Chi-square test, with P < 0.05 considered statistically significant.

The primary outcome of this study was to assess the appropriateness of cephalosporin prescriptions based on clinical indications, dose, frequency, duration, route of administration, and adherence to antimicrobial stewardship guidelines. The secondary outcomes included identifying commonly isolated pathogens from culture reports, evaluating antimicrobial susceptibility and resistance patterns, determining co-prescribed antibiotics and drug interactions, analyzing trends in empirical versus definitive therapy, monitoring antimicrobial de-escalation practices, and documenting intravenous-to-oral switch patterns.

RESULTS

Of the 288 patients included in the study, 146 (50.7%) were male and 142 (49.3%) were female, showing a slightly higher proportion of male participants. The mean age of the study population was 52.97 ± 19.05 years and 42% of the patients belonged to the elderly age group. The diagnostic distribution of the study population is presented in Table 1 and the distribution of cephalosporin is represented in Figure 1.

Table 1.

Distribution of the study population based on the diagnosis (n=288 patients)

Diagnosis	Number of patients (n=288)
Gastrointestinal infection	81 (28.1)
Urinary tract infection	75 (26.0)
Lower respiratory tract infection	48 (16.7)
Viral infection	23 (8.0)
Skin and soft tissue infection	19 (6.6)
Enteric fever	9 (3.1)
Upper respiratory tract infection	5 (1.7)
Reproductive tract infection	5 (1.7)
Sepsis	5 (1.7)
Neutropenic fever	3 (1.0)
Meningitis	1 (0.3)

Statistical analysis: Data are summarized using the descriptive statistics (frequency and percentage). n: Number of patients

Figure 1.

Individual cephalosporin usage among the study population

The most frequently observed comorbidity was diabetes mellitus with systemic hypertension (17.0%), followed by diabetes mellitus alone (12.2%) and hypertension alone (9.0%). Other notable comorbidities included hypothyroidism (5.9%) and diabetes with hypertension and coronary artery disease (5.6%). Less common comorbidities, included diabetes with hypothyroidism, bronchial asthma, diabetes with systemic hypertension, chronic kidney disease, seizure disorder, and chronic liver disease. Chronic obstructive pulmonary disease, Parkinson’s disease, and malignancy were observed in a smaller number of patients. Approximately 30.2% of the patients had no documented comorbidities.

In addition to infectious diseases, cephalosporins were prescribed for certain noninfectious conditions, including acute febrile illness (n = 12, 4.2%), myeloproliferative disorder (n = 1, 0.3%), and deep-vein thrombosis (n = 1, 0.3%).

A total of 383 cephalosporins were prescribed in 288 patients. Of these, 97.4% were third-generation cephalosporins (3GCs), 1.8% were second-generation cephalosporins, 0.5% were fourth-generation cephalosporins, and 10.3% were first-generation cephalosporins.

Of the 288 participants, 89.9% received empirical therapy, while 10.1% received definitive therapy. Empirical cephalosporin therapy was most frequently prescribed for gastrointestinal tract infections (n = 70, 24.3%), followed by lower respiratory tract (n = 48, 16.7%) and urinary tract infections (UTIs) (n = 9, 3.1%). Definitive therapy with cephalosporins was most frequently administered for gastrointestinal tract infections (n = 11, 3.8%), followed by UTI (n = 9, 3.1%).

Culture test was performed in 63% (n = 181) patients and the reports revealed. Among these, bacterial growth was observed in 13.9%, viral growth in 1.4%, and fungal growth in 0.3% of the cases. In addition, 47.2% (n = 136) had no growth. No growth was reported in 47.2% (n = 136) of samples. Bacterial growth enabled de-escalation from empirical to definitive therapy in 29 patients, demonstrating the clinical importance of microbiological confirmation in guiding antimicrobial therapy. A highly significant association was observed between the type of therapy (empirical vs. definitive) and culture positivity (χ² = 192.01, df = 1, P < 0.001), confirming that definitive therapy was strongly influenced by positive culture results.

Bacterial cultures reports showed, 10% were Gram-positive bacteria and 90% were Gram-negative bacteria. Escherichia coli was the most prevalent organism, isolated in 12 patients (30%). This was followed by ESBL-producing E. coli (n = 7; 17.5%), Klebsiella pneumoniae (n = 6; 15.0%), and carbapenemase-producing Klebsiella (n = 3; 7.5%). Other organisms included Pseudomonas aeruginosa (n = 2; 5%), Salmonella Paratyphi A (n = 2; 5%), and carbapenemase-producing E. coli, Citrobacter koseri, diarrheagenic E. coli, Enterococcus raffinosus, and Enterococcus faecalis (n = 1 each; 2.5%).

The cephalosporin susceptibility and resistance patterns of the isolated organisms are presented in Table 2.

Table 2.

Cephalosporin sensitivity and resistance pattern among the study population (n=40 isolates)

Organism	Ceftazidime		Cefazolin		Cefepime		Ceftriaxone
	Sensitivity, n (%)	Resistance, n (%)	Sensitivity, n (%)	Resistance, n (%)	Sensitivity, n (%)	Resistance, n (%)	Sensitivity, n (%)	Resistance, n (%)
Carbapenemase-producing K. pneumonia (n=3; 7.5%)	2 (5)	1 (2.5)	-	2 (5)	-	2 (5)	-	3 (7.5)
Carbapenemase-producing E. coli (n=1; 2.5%)	-	1 (2.5)	-	-	-	1 (2.5)	-	1 (2.5)
C. koseri (n=1; 2.5%)	-	-	-	-	1 (2.5)	-	1 (2.5)	-
E. coli (n=12; 30%)	2 (5)	4 (10)	3 (7.5)	3 (7.5)	5 (12.5)	5 (12.5)	5 (12.5)	6 (15)
ESBL E. coli (n=7; 17.5%)	4 (10)	2 (5)	-	6 (15)	2 (5)	5 (12.5)	1 (2.5)	6 (15)
K. pneumonia (n=6; 15%)	2 (5)	2 (5)	3 (7.5)	1 (2.5)	3 (7.5)	2 (5)	5 (12.5)	-
P. aeruginosa (n=2; 5%)	2 (5)	-	-	-	1 (2.5)	1 (2.5)	-	-
S. aureus (n=1; 2.5%)	-	-	1 (2.5)	-	1 (2.5)	-	-	1 (2.5)
Salmonella para typhi A (n=2; 5%)	-	-	-	-	2 (5)	-	2 (5)	-
Organism	Cefoxitin		Cefixime		Cefuroxime		Cefotaxime
	Sensitivity, n (%)	Resistance, n (%)	Sensitivity, n (%)	Resistance, n (%)	Sensitivity, n (%)	Resistance, n(%)	Sensitivity, n (%)	Resistance, n (%)
Carbapenemase-producing K. pneumonia (n=3; 7.5%)	-	-	-	1 (2.5)	-	3 (7.5)	-	-
Carbapenemase-producing E. coli (n=1; 2.5%)	-	-	-	1 (2.5)	-	-	-	-
C. koseri (n=1; 2.5%)	-	-	-	-	-	-	-	-
E. coli (n=12; 30%)	-	-	1 (2.5)	3 (7.5)	-	4 (10)	1 (2.5)	-
ESBL E. coli (n=7; 17.5%)	-	1 (2.5)	1 (2.5)	1 (2.5)	-	4 (10)	-	1 (2.5)
K. pneumonia (n=6; 15%)	-	-	1 (2.5)	-	1 (2.5)	1 (2.5)	-	-
P. aeruginosa (n=2; 5%)	-	-	-	-	-	-	-	-
S. aureus (n=1; 2.5%)	-	-	-	-	-	-	-	-
Salmonella para typhi A (n=2; 5%)	-	-	2 (5)	-	-	-	-	-

Statistical analysis: Descriptive summary of sensitivity and resistance patterns. n=Number of organisms isolated, E. coli=Escherichia coli, S. aureus; Staphylococcus aureus, P. aeruginosa=Pseudomonas aeruginosa, Klebsiella pneumonia=Klebsiella pneumonia, C. koseri=Citrobacter koseri, ESBL: Extended-spectrum beta-lactamase

Other antibiotics were coprescribed with cephalosporins based on clinical indications. Among these, azithromycin was the most frequently co-administered antibiotic (29.7%), followed by metronidazole (12.4%) and piperacillin–tazobactam (11.9%). The complete distribution of co-administered antibiotics is shown in Table 3 (n = 202).

Table 3.

Other antibiotics co-administered with cephalosporin (n=202 prescriptions)

Other antibiotics	Frequency (n=202), n (%)
Azithromycin	60 (29.7)
Metronidazole	25 (12.4)
Piperacillin–Tazobactam	24 (11.9)
Doxycycline	20 (9.9)
Meropenem	16 (7.9)
Nitrofurantoin	13 (6.4)
Clindamycin	12 (5.9)
Levofloxacin	8 (4.0)
Amoxycillin	6 (3.0)
Ciprofloxacin	5 (2.5)
Teicoplanin	3 (1.5)
Amikacin	2 (1.0)
Fosfomycin	2 (1.0)
Aztreonam	1 (0.5)
Faropenam	1 (0.5)
Vancomycin	1 (0.5)
Penicillin	1 (0.5)
Rifaximin	1 (0.5)

Statistical analysis: Frequency distribution only. n=Number of prescriptions

Among the 383 cephalosporin prescriptions, 73.4% were administered intravenously, while 26.6% were administered orally. An intravenous-to-oral switch was implemented in 117 patients based on clinical improvement, ability to tolerate oral medication, and availability of appropriate oral formulations. The most common conversion was from cefoperazone (IV) to cefixime (oral) in 74 patients (25.7%), followed by ceftriaxone (IV) to cefixime (oral) in 28 patients (9.7%). Other conversions included cefoperazone to cefpodoxime (n = 7; 2.4%), cefoperazone to cefuroxime (n = 3; 1.0%), cefotaxime to cefixime (n = 3; 1.0%), cefepime to cefixime (n = 1; 0.3%), and ceftriaxone to cefuroxime (n = 1; 0.3%).

All 383 cephalosporin prescriptions were assessed for appropriateness based on standard guidelines. Of these, 259 prescriptions (67.6%) were considered appropriate, while 124 prescriptions (32.4%) were deemed inappropriate. The appropriateness of individual cephalosporins is summarized in Table 4 and Figure 2.

Table 4.

Appropriateness and inappropriateness of individual cephalosporins (n=383 Cephalosporin prescribed)

Cephalosporin	Appropriate, n (%)	Inappropriate, n (%)	Total
Cefoperazone	145 (37.9)	46 (12.0)	191
Ceftriaxone	41 (10.7)	37 (9.7)	78
Cefixime	65 (17.0)	25 (6.5)	90
Ceftazidime	1 (0.3)	1 (0.3)	2
Cefotaxime	0	7 (1.8)	7
Cefpodoxime	3 (0.8)	2 (0.5)	5
Cefazolin	0	1 (0.3)	1
Cefuroxime	4 (1.0)	3 (0.8)	7
Cefepime	0	2 (0.5)	2

Statistical analysis: Data are summarized using the descriptive statistics (frequency and percentage). n=Number of cephalosporin prescribed

Figure 2.

Proportion of inappropriateness of cephalosporin dose, frequency, duration, and indication

Among the 288 prescriptions analyzed, 5.9% (n = 17) demonstrated potential drug–drug interactions involving cephalosporins. The most common interaction was between ceftriaxone and Ringer’s lactate (n = 15; 5.2%), an incompatibility associated with calcium-mediated precipitation. Less common interactions included ceftriaxone with amikacin (n = 1; 0.3%) and cefoperazone with torsemide (n = 1; 0.3%), both of which may increase the risk of nephrotoxicity.

DISCUSSION

Cephalosporins are among the most commonly prescribed antibiotics and require close monitoring to ensure their rational use in the context of increasing antimicrobial resistance.

Of the 288 patients enrolled during the study period, 201 (69.8%) had one or more comorbidities. Among these, the most prevalent conditions were diabetes mellitus (42%), followed by systemic hypertension (29.5%) and hypothyroidism (9.7%). Patients with diabetes are more susceptible to infections, which occur more frequently and tend to be more severe than in individuals without diabetes largely due to immune dysfunction and poor glycemic control, similar to the findings reported in the study by Rokaya et al.[10]

Cephalosporins were most frequently prescribed for gastrointestinal infections (28.1%), followed by UTIs (26.0%) and lower respiratory tract infections (16.7%). This trend is consistent with findings reported in previous studies.[11]

Our analysis demonstrated that 3GCs were prescribed in 97.4% of the cases. This finding is comparable to earlier studies that have reported a higher use of third-generation agents because of their broad spectrum of activity and enhanced gram-negative coverage.[12] However, no single third-generation cephalosporin can be universally recommended for all infections, as important differences exist in terms of gram-positive coverage, anaerobic activity, and antipseudomonal efficacy. In the present study, cefoperazone–sulbactam (49.9%) was the most frequently prescribed agent, particularly for respiratory tract infections and UTIs.

Regarding microbiological confirmation, although 63% of patients underwent culture testing, only 13.9% of samples yielded positive results. This low positivity rate may be attributed to the prior initiation of empirical antibiotic therapy, which can reduce bacterial load and impair microbial detection. In addition, a proportion of clinically suspected infections may have been viral or nonbacterial in origin. Variations in specimen timing, collection technique, and laboratory processing may have further contributed to the low culture positivity rate. These findings highlight the need for improved diagnostic stewardship, including timely specimen collection, to enhance culture yield and facilitate targeted antimicrobial therapy.

About 89.9% of the patients were treated empirically with cephalosporins. This was due to the fact that microbiological data are often not available in 24–72 h. First-line therapy was dependent on the clinical judgment of the physician, clinical status of the patient, and laboratory values. In a study by John et al., ceftriaxone was frequently used empirically because of its high antibacterial potency, wide range of activity, and minimal toxicity.[11]

Gopali reported that cefoperazone (40%) and cefuroxime (21.1%) were the most commonly used antibiotics.[12] In contrast, our study demonstrated a predominant use of cefoperazone – sulbactam, which was supported by the repeated isolation of gram-negative organisms from culture samples.

Among the 288 patients, antibiotic therapy was de-escalated in 29 cases based on culture and sensitivity reports. However, in 11 cases, de-escalation was not performed, either because patients were discharged before reports were available or because physicians continued the same cephalosporin regimen despite laboratory evidence suggesting an alternative agent.

A total of 202 antibiotics were co-administered in 100 (34.7%) study participants who received cephalosporins. The data indicated that azithromycin was the most frequently co-administered antibiotic (n = 60, 29.7%), followed by metronidazole (n = 25, 12.4%). These medications were prescribed based on the clinical diagnosis.

Evaluated the indication, dosage, frequency, and duration of cephalosporin treatment based on ICMR guidelines. With respect to indications, 106 (36.8%) patients were prescribed cephalosporins inappropriately. For acute gastroenteritis, cefoperazone-sulbactam is the recommended drug of choice; alternatively, piperacillin-tazobactam is advised in cases of blood in stool or a positive culture. However, in our study, cefepime, cefotaxime, and ceftriaxone were used. Similarly, for cystitis, nitrofurantoin is the preferred drug; however, cefoperazone-sulbactam, ceftriaxone, and cefotaxime were administered. For pharyngitis, piperacillin-tazobactam and azithromycin are the recommended drugs; however, ceftriaxone and cefoperazone-sulbactam were used. Notably, the cases of acute febrile illness were treated with antibiotics, which is deemed inappropriate.[13]

Our analysis of cephalosporin prescribing practices revealed several critical areas where adherence to the established guidelines could be strengthened, underscoring the ongoing need for enhanced antimicrobial stewardship. Deviations from recommended dosing, frequency, and duration of administration were particularly notable.

A significant proportion of patients (19.4%, or 56 patients) received inappropriate cephalosporin dosages, especially for common infections such as UTIs, cellulitis, and lower respiratory tract infections. A concerning pattern was, underdosing with cefoperazone-sulbactam, which was given at 1.5 g instead of the recommended 3 g for UTIs and cellulitis. This not only risks suboptimal therapeutic outcomes but also contributes to the development of resistant microbial strains. Among the study population, nine patients exhibited elevated creatinine levels, and dosage adjustments were not carried out in four patients receiving cefoperazone-sulbactam.

Regarding the frequency of cephalosporin administration, inappropriate regimens were identified in 25 patients (8.7%). For example, ceftazidime-avibactam for carbapenem-resistant Klebsiella pneumoniae-induced UTIs was administered at 1.25 g twice daily, contrary to the recommended 2.5 g thrice daily. Similarly, for severe pancreatitis, cefoperazone-sulbactam was prescribed twice daily instead of the appropriate 3 g thrice daily. Such discrepancies can compromise treatment effectiveness and potentially drive resistance development.

The mean duration of cephalosporin therapy was 4.87 ± 2.70 days. The guidelines recommend 3–5 days of treatment for mild-to-moderate urinary and lower respiratory tract infections and 4–7 days for intra-abdominal infections and cellulitis. However, in 64 patients (22.2%), the treatment duration deviated from the ICMR recommendations, and our study observed that treatment courses were shorter than the recommended guidelines.[13]

Analyzing administration routes, most prescriptions were intravenous (73.4%), with a commendable switch to oral administration occurring in 40.6% of patients. This IV-to-oral transition is vital for cost-effectiveness and patient comfort, with cefixime being the most common oral choice.

The exclusion of patients receiving cephalosporins as surgical prophylaxis was intentional, as their antibiotic use followed standardized preventive protocols rather than active infection management. Similarly, intensive care unit patients were excluded owing to limited access to records and the complexity of antimicrobial prescribing in critical care settings, which often involves broad spectrum and frequently modified regimens. Including these populations could have confounded the analysis and affected data consistency.

Several limitations should be acknowledged. The study was conducted over a relatively short period of 6 months at a single institution, which may restrict the generalizability of results. In addition, the heterogeneous nature of infections, varying resistance patterns, and patient-specific factors such as comorbidities and renal function may have influenced treatment decisions and outcomes. These factors highlight the challenges in standardizing antibiotic prescribing practices across the diverse clinical contexts.

CONCLUSION

Our study identifies a trend toward increased use of cephalosporins, especially 3GCs. Of these 32.4% were not in accordance with the ICMR guidelines. To enhance compliance with these guidelines, we recommend expediting the availability of culture and sensitivity reports and improving the accessibility of antibiotic guidelines through the hospital’s information system. There is a need for improved adherence to guidelines to ensure appropriate use of cephalosporins. An implementation of an effective antibiotic stewardship program with a multidisciplinary approach may improve the compliance and reduce antibiotic resistance.

AUTHOR CONTRIBUTION

Pavithra. K: Concepts, Design, Intellectual content, Data acquisition, Data analysis, Statistical analysis, Manuscript preparation, Manuscript editing, Intellectual content, Literature search. Shajan. R. S: Concepts, Intellectual content, Literature search, Data acquisition, Data analysis, Statistical analysis, Manuscript preparation, Manuscript editing.

Mohamed Parvis. A: Design, Clinical studies, Data acquisition, Data analysis, Statistical analysis, Manuscript editing, Manuscript review. Anto Melvin Raj. S: Manuscript review, Data acquisition, Clinical studies, Design. Dr. Priya. B: Intellectual Content, Manuscript Review, Guarantor. Dr. Ramalakshmi: Intellectual Content, Manuscript preparation, Manuscript Review, Guarantor.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.