Utilization pattern and outcomes of piperacillin-tazobactam in a multispecialty hospital: A cross-sectional analysis

INTRODUCTION

Infectious diseases are illnesses caused by pathogenic microorganisms or their toxic byproducts and can be transmitted through contact with infected animals or consumption of contaminated food and water.^[1] Vaccination can prevent many infectious diseases, and antibiotics have facilitated advanced medical procedures such as oncology treatments, cardiac surgeries, and organ transplantation, thereby significantly improving life quality and expectancy.^[2] However, the improper use of antibiotics, without adherence to clinical guidelines, has led to the emergence of antimicrobial resistance, rendering infections increasingly difficult or sometimes impossible to treat.^[3] This issue has persisted for decades, complicating the management of both common and critical infections. Piperacillin-tazobactam (PTZ) is a broad-spectrum antibiotic that combines a ureidopenicillin with a beta-lactamase inhibitor.^[4] It exhibits bactericidal activity against a wide range of gram-positive and gram-negative aerobic and anaerobic bacteria by inhibiting septum and cell wall synthesis.^[5] This combination extends its antibacterial spectrum to include many β-lactamase-producing organisms, such as Staphylococci, Enterobacteriaceae, Haemophilus influenzae, and Bacteroides species.^[6] PTZ is frequently utilized in the treatment of intra-abdominal infections, nosocomial infections, community-acquired pneumonia, skin and soft tissue infections, and gynecological infections.^[7] It is contraindicated in patients with known hypersensitivity to any penicillin, cephalosporin, or β-lactamase inhibitor.^[8] To mitigate the development of resistant bacteria and preserve the efficacy of PTZ and other antibacterial agents, it should be prescribed exclusively for confirmed or strongly suspected bacterial infections.^[9] Prescription auditing forms a crucial component of a comprehensive clinical audit aimed at enhancing patient care and clinical outcomes through systematic review of practices against established criteria and the implementation of necessary changes.^10] Routine and timely audits of antibiotic prescriptions can prevent irrational antibiotic use and improve the overall quality of healthcare delivery. PTZ has been widely researched regarding its usage and outcomes in various clinical environments. Studies indicate that educating healthcare providers on alternative treatments can significantly reduce the utilization of PTZ.^[11] Additionally, critically ill adults receiving PTZ did not experience an increased incidence of adverse renal events and exhibited improved neurologic outcomes compared to those treated with anti-pseudomonal cephalosporins.^[12] In patients undergoing open pancreatoduodenectomy, the use of PTZ as perioperative prophylaxis has been shown to decrease the incidence of postoperative surgical site infections, pancreatic fistula, and sepsis, endorsing its application as standard care in this context.^[13] Furthermore, extended infusion of PTZ has been linked to lower mortality rates, reduced incidence of Clostridium difficile infections, and cost savings when compared to standard infusion, highlighting its advantages in non-critically ill patients.^[14] Lastly, PTZ has proven to be an effective alternative to carbapenems for treating nosocomial pneumonia caused by extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, with comparable clinical outcomes observed between the two treatments.^[15] The audit of PTZ usage has been the subject of limited studies. In a prospective study conducted at a large urban tertiary care hospital in Canada, the utilization of PTZ was evaluated based on several criteria: adherence to hospital guidelines, appropriateness of antibiotic selection for the clinical scenario, and proper duration of therapy. The study found that 38.5% of PTZ use was inappropriate, and the cost avoidance associated with appropriate usage was also calculated.^[16] Another study assessed the appropriate use of PTZ in a community health system over 3 months, involving 500 patients across four hospitals. The overall appropriate use rate was 71.5%, with hospitals A and B both demonstrating an 82% appropriateness rate, compared to 64% and 58% for hospitals C and D, respectively. This assessment followed the IDSA guidelines Shah and Ryzner, 2013.^[17] Similarly, a study conducted over four months with 200 patients at a tertiary care teaching hospital found that PTZ was used appropriately in 73.5% of cases, with inappropriate use identified in 26.5% of cases. Another study with a comparable sample size reported a 93.24% rate of appropriate use of PTZ.^[18] The objective of our audit is to monitor and optimize the administration of PTZ in a multi-specialty hospital in Chennai illustrated in Figure 1.

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Figure 1:

Schematic representation of the piperacillin-tazobactam utilization and outcomes in a multi-speciality hospital.

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MATERIAL AND METHODS

RESULTS

The study included all patients who were prescribed PTZ and met the inclusion criteria during the study period. Table 1 summarizes the basic information about the 245 eligible patients in the study. Out of these patients, 141 (57.6%) were male, and 104 (42.4%) were female, with a mean age of 62.59±15.82. The average weight, height, and BMI were 66.61±14.53, 161.2±7.31, and 25.47±5.02, respectively. Around 31% of admissions went to the ICU, and 69% went to the general ward. We documented vital signs on admission, including temperature, oxygen saturation, blood pressure (systolic and diastolic), pulse rate, respiratory rate, and mean arterial pressure. We performed laboratory tests, including blood cell analysis, glucose and lipid levels, and other biochemical markers, when we started PTZ therapy. Most of the reviewed patients were from the general ward, and their hospital stays ranged from 6 to 10 days.

The study included 245 patients, with various co-morbidities observed among them. The most prevalent co-morbidity was diabetes mellitus, affecting 130 patients (53.1%), followed by hypertension, present in 101 patients (41.3%). Other significant co-morbid conditions included heart disease in 36 patients (14.7%), cancer in 13 patients (5.3%), and chronic obstructive pulmonary disease (COPD) in 11 patients (4.5%). Acute kidney disease was found in nine patients (3.7%), while chronic kidney disease was observed in seven patients (2.9%). Hypothyroidism and bronchial asthma each affected nine (3.7%) and eight (3.3%) patients, respectively. Cerebrovascular accident and bronchial asthma were each present in eight patients (3.3%). Parkinsonism was noted in six patients (2.4%), and rheumatoid arthritis in five patients (2.0%). Decompensated chronic liver disease was the least common, affecting four patients (1.6%). The study participants reported having at least one comorbidity is 130 (53.1%), and patients reported having two or more co-morbidities 101(41.3%).

Overall, the data highlight the diverse range of co-morbidities present in the study population, with diabetes mellitus and hypertension being the most common were illustrated in Table 2.

Table 3 represents the clinical indications for which PTZ was prescribed by physicians. The predominant indication was UTI, representing 26.1% of prescriptions. UTI was followed closely by medical prophylaxis, which constituted 25.7% of the prescriptions. Other significant therapeutic indications included sepsis (18.8%), cellulitis (13.9%), lower respiratory tract infection (12.7%), aspiration pneumonitis (6.1%), and intra-abdominal infection (6.1%). Moreover, PTZ was prescribed for COPD (5.7%), pyelonephritis (4.9%), hospital-acquired pneumonia (HAP) (4.5%), diabetic foot ulcer (4.1%), and febrile neutropenia (0.4%).

These findings underscore UTI and medical prophylaxis as the predominant reasons for PTZ utilization during the study period. Additionally, these results highlight the importance of appropriate antibiotic stewardship practices in healthcare settings. The median LOS for both appropriate and inappropriate hospital admissions was 8.0 days. However, there was a difference in the interquartile range (IQR). The IQR for appropriate admissions (n=242) was 5.0 days, while for inappropriate admissions (n=3), it was 3.75 days. This suggests that while the central tendency of LOS was the same, the spread of data for appropriate admissions was slightly wider.

The majority of PTZ prescriptions were for renal and UTI (32.2%), followed by respiratory infections (25.3%) and skin and soft tissue infections (21.6%). Among the 245 PTZ prescriptions, approximately 18% were for bloodstream infections, 13.5% for surgical site infections, 10.2% for intra-abdominal infections, 2.9% for bone and joint infections, and 2.4% for central nervous system infections has been tabulated in Table 4. The analysis of PTZ microbial profile revealed that urine was the most common source of culture, which accounted for 40.4% of cases, followed by sputum (9.8%), pus (9.0%), tissue (2.9%), blood (0.8%), tracheal (0.4%), and pleural (0.8%) cultures. Most of the isolated organisms were gram-negative (29.0%), a few were gram-positive (0.4%), and no organisms grew in 28.2% of cases. The antibiogram results indicated that 8.2% of the organisms responded well to PTZ, 1.2% had moderate response, and 4.9% were not responsive. Notably, 85.7% of cases lacked antibiogram data.

This emphasizes the prevalence of urine cultures and gram-negative organisms, underscoring the crucial role of culture and sensitivity testing in directing effective antibiotic treatment has been shown in Table 5.

In this study, we assessed the appropriate use of PTZ based on the IDSA guidelines we found that PTZ was used appropriately with a percentage of 98.8. This study also calculated the therapeutic Approach of PTZ, results indicated that empirical use was 63.7% followed by Rational (18%), and 18.4% were treated surgically. This standardized approach highlights the consistent administration practices of PTZ in clinical settings. The drug regime of PTZ was tabulated in Table 6.

Over the study period, lincosamide and macrolides were the two most commonly selected antibiotics, along with PTZ, being prescribed on average 12.7% and 4.5% of occasions, respectively. Whereas rarely prescribed antibiotics include nitroimidazole, tetracycline, and fluoroquinolones, as shown in Table 7. The outcomes of 245 cases treated with PTZ were analyzed based on infections caused by E. coli, Klebsiella, Pseudomonas, Enterococcus, and Achromobacter. Overall, 64.9% of cases improved, 16.8% did not improve, and 18.4% resulted in death. Specifically, for E. coli infections, 65.7% improved, 14.4% did not improve, and 20% expired. Klebsiella infections showed a 46.4% improvement rate, 14.3% did not improve, and 39.3% expired. Pseudomonas infections had a high improvement rate of 90.9%, with 9.1% not improving and 9.1% expiring.

Enterococcus infections showed no improvement, with 100% of cases either not improving or expiring. Similarly, Achromobacter infections showed no improvement, with 100% of cases not improving. The data highlights the observed improvement high efficacy of PTZ in treating Pseudomonas infections, while infections caused by Enterococcus and Achromobacter had poor outcomes, were demonstrated in Table 8.

The mortality among patients, the most important reasons were septic shock (19), cardiogenic shock (10), Covid 19 pneumonia (5), at the end of the treatment with PTZ shown in Table 9.

Table 10 describes the predictors of mortality among study participants. The outcome measure includes GCS Score (13.45±3.26), Apache II (17.78±6.59), SOFA Score (3.30±2.05), and pitt Bacteraemia Score (1.29±2.46) to account for a survivorship bias.

The dosage of PTZ used varies according to the clinical indication; the most common dose prescribed was 4.5 g every 8 hours in 81.2% (156/192) of the patients. In terms of duration of treatment, most of the patients (121/192) (63%) received PTZ for 1-5 days. Table 11 shows the dosage regimen of PTZ used.

Among the 245 patients, outcomes were assessed based on age categories as detailed in Table 12. Of the 159 patients who showed improvement, 56 were in the 65-79 years age group. For the 45 patients who did not improve, 16 were in the 50-64 years age range. Additionally, of the 27 patients who expired, the majority were in the 65-79 years age group, as illustrated in Table 12. In this study, the culture samples were obtained from 157 patients, as detailed in the table. Pathogens were identified in 72 of these cases (29.4%). The most frequently identified pathogen was E. coli, found in 35 patients, followed by Klebsiella in 28 patients, Pseudomonas in 11 patients, and both Enterococcus and Achromobacter in 1 patient each. gram-negative organisms were predominant, comprising a total of 71 cases (29%) shown in Figure 2.

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Figure 2:

Types of infectious organisms identified from culture.

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The antibiogram results highlight the varying levels of effectiveness of different antibiotics against a bacterial strain. High susceptibility is observed with colistin, amikacin, imipenem, and netilmicin, each showing over 99% effectiveness. Conversely, high resistance is noted with cefazolin, cefuroxime, ceftriaxone, ceftazidime, and cefepime, each exhibiting over 68% resistance. Antibiotics like amoxicillin-potassium clavulanic acid, tetracycline, and trimethoprim-sulphamethoxazole show moderate effectiveness, with significant portions of the strain being resistant. In Figure 3, the above data underscores the importance of selecting appropriate antibiotics based on susceptibility patterns to effectively treat infections and minimize resistance development.

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Figure 3:

Overall antibiotic sensitivity test performed in the study population.

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DISCUSSION

PTZ is recognized as a potent antibiotic capable of treating a broad spectrum of bacterial infections, encompassing both gram-positive and gram-negative, as well as aerobic and anaerobic bacteria.^[5] PTZ was identified as the second most commonly prescribed antibiotic for infections in critically ill patients, comprising 2.5% of all antimicrobial treatments in this group, and ranked among the top five antibiotics for non-critically ill patients.^[19] In this study, we examined the utilization of PTZ in a multi-specialty hospital over the past 6 months, using aggregated data. The research was conducted in the general in patients ward and intensive care unit (ICU), with a higher proportion of patients (69%) admitted to the general ward compared to 31% in the ICU.^[20-22] Eligible participants included patients aged 18 years or older who were admitted to either ward and received any dose of PTZ. The mean age of the patients was 62.59 ± 15.82 years, with 57.6% being male.^[23-25] Baseline characteristics and vital parameters were recorded on a pre-prepared CRF based on medical records. The suspected source of infection was determined through microbiological results from culture samples collected up to 48 hours before treatment initiation. These samples included 99 urine, 24 sputum, 22 pus, seven tissue, two blood, two pleural, and one tracheal sample. The identified pathogens included E. coli (35 cases) from urine, sputum, pus, and tissue cultures; Klebsiella (28 cases) from all mentioned cultures except tissue; and Pseudomonas (11 cases) from the same samples as E. coli. Enterococcus and Achromobacter were each isolated from urine samples.^[22] Cultures were performed for approximately half of the patients, with P. aeruginosa, E. coli, and S. aureus being the most commonly isolated bacteria.^[26,27] In our study, gram-negative bacteria predominated, with E. coli being the most frequently isolated pathogen. PTZ was most commonly prescribed for renal infections (32.2%), followed by respiratory infections (25.3%) and skin and soft tissue infections (21.6%), differing from other studies’ findings for these indications.^[16] PTZ was frequently used for empiric therapy, primarily prescribed upon admission for suspected respiratory tract infections (29%) and urinary tract infections (26.1%), consistent with the findings of Remesh et al., 2013.^[28] Whereas^[29] observed that 31.4% of respiratory infections diagnosed at admission required empirical antibiotic treatment. Our study primarily evaluated the impact of empirical PTZ therapy. While the treatment regimen was adjusted for many patients, empirical therapy remains crucial, especially for bacteremic patients.^[30,31] However, inappropriate use of PTZ was identified in 24 out of 64 UTI patients, four out of 14 COPD cases, and four out of 11 HAP instances.^[32] The primary outcomes of our study included assessing the appropriateness of PTZ use, determined by dose, frequency, and duration of treatment as per the IDSA guidelines. Previous studies reported a 90% appropriateness rate for PTZ use. This cross-sectional study identifies high appropriateness of PTZ usage (98.8%) aligned with IDSA guidelines and institutional stewardship protocols. The unusually high appropriateness rate compared to other studies (e.g., Beahm and Fryters,^[16] 38.5% inappropriate use) is attributable to real-time clinical pharmacist review, hospital policy enforcement, and predefined protocol adherence.^[33] The appropriateness varied among different indications, with the highest appropriate use in sepsis (26.3%), followed by UTIs (22.4%) and cellulitis (17.3%). The lowest rates of appropriate use were observed in cases of HAP, pyelonephritis, and COPD.^[34] The dosage of PTZ varied based on clinical indications, with 4.5 g every 8 hours being the most frequently prescribed dose, administered to 81.2% of patients. The antibiotic dosage of 4.5 g for every 8 hours, which was consistent with IDSA guidelines for PTZ usage.^[5] The least common treatment duration was between 6 to 10 days, particularly for pyelonephritis. Our hospital did not frequently use the 3.375 g dosage.^[30] The study revealed variability in the duration of antibiotic treatment, with 63% of patients receiving PTZ for 5 days, 32.3% for 10 days, and 4.7% for 15 days. The total number of doses prescribed averaged 11.80 ± 8.26 per patient. Additionally, 94 patients received combination therapy, with lincosamide being the most frequently combined agent (12.7%). While our study did not record any adverse events, previous research has consistently highlighted the total dose and duration of PTZ therapy as significant risk factors for adverse events.^[35-37] Secondary outcomes included the LOS and hospital mortality. To evaluate patient outcomes, such as morbidity, mortality, and illness severity, various scoring systems are utilized in medical intensive care units. In our study, we calculated the mortality rate using the SOFA and APACHE II scores. The mean APACHE II score among patients was 17.78 ± 6.59.^[23] The Charlson Comorbidity Index, which assesses chronic illness severity, was also calculated, yielding a mean score of 3.30 ± 2.057. Additionally, the Pitt Bacteremia score, which evaluates the severity of acute conditions, averaged 1.29 ± 2.463. The overall mortality rate in the study population was 18.4%, with specific rates varying by age category as shown in Table 9.^[21] Microbiological cure rates and treatment outcomes with PTZ varied based on the infecting organisms. For instance, 23 patients with E. coli infections improved, followed by 13 with Klebsiella infections, and 10 with Pseudomonas infections. Due to data limitations, we could not isolate the LOS from the start of PTZ therapy,^[19] so we analyzed the total length of stay, including the period before therapy initiation. The observed improvement rate of 90.9% in Pseudomonas infections reflects clinical response, not efficacy in the interventional trial sense. No control or comparator groups were included. A recent retrospective study indicated an increased risk of mortality in individuals receiving broad-spectrum antimicrobials, including PTZ, as initial monotherapy for community-acquired pneumonia, potentially due to inadequate coverage of atypical pathogens. Clinical cure in our study was defined by patient survival upon discharge, normalization of vital signs, white blood cell count, and temperature, along with the absence of additional antibiotic requirements.^[38]

CONCLUSION

This study evaluates the utilization of PTZ in a multispecialty hospital, revealing that 98.8% of prescriptions adhered to established guidelines. Hospital admissions frequently use PTZ to treat respiratory and urinary tract infections due to its high effectiveness in clinical improvement against a wide range of bacterial infections. We assessed patient outcomes using standardized scoring systems, such as the APACHE II score, which revealed a moderately high severity of illness among the patient cohort. However, the overall mortality rate was 18.4%, highlighting the effectiveness of PTZ for critically ill patients. Patients infected with common pathogens such as E. coli, Klebsiella, and Pseudomonas showed significant clinical improvements, including faster recovery and reduced infection severity, with gram-negative bacteria being the most frequently isolated pathogens. The majority of patients experienced a relatively short hospital stay, indicating a prompt therapeutic response to PTZ treatment that facilitated a quick recovery. However, the study identified survivorship bias, potentially skewing the results by primarily calculating the mortality and morbidity severity scores for patients who survived until discharge. The findings emphasize the critical importance of adhering to empirical use guidelines to optimize clinical outcomes and minimize the risk of adverse events such as treatment failure and drug resistance. Further prospective, controlled studies with appropriate statistical modeling and trial registration are essential to validate these outcomes and assess long-term PTZ effectiveness.