Next Article in Journal
Effects of Pharmacist-Led Interventions Regarding Adult Patients with Type 2 Diabetes Mellitus in Mexico: A Systematic Review
Next Article in Special Issue
Discrepancy between Subjective and Objective Measurements for the Evaluation of Medication Adherence—A Cross-Sectional Study in Patients with Cardiovascular Diseases
Previous Article in Journal
Future Healthcare Workers and Ecopharmacovigilance: Where Do We Stand?
Previous Article in Special Issue
Pharmacist-Led Deprescribing of Opioids and Benzodiazepines in Older Adults: Examining Implementation and Perceptions
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Efficacy of Ciprofloxacin in Treating Gram-Negative Infections: Does Obesity Matter?

1
Department of Pharmaceutical Care Services, King Abdulaziz Medical City, Ministry of the National Guard-Health Affairs, Jeddah 22384, Saudi Arabia
2
King Abdullah International Medical Research Center, Jeddah 22384, Saudi Arabia
3
King Saud bin Abdulaziz University for Health Sciences, Jeddah 22384, Saudi Arabia
4
Infection Prevention and Control Department, King Abdulaziz Medical City, Ministry of the National Guard-Health Affairs, Jeddah 22384, Saudi Arabia
5
Ashira Al-Eshrafi Health Center, Taif Health Cluster, Taif 21944, Saudi Arabia
6
Pharmaceutical Care Services, King Faisal Medical Complex, Taif Health Cluster, Taif 21944, Saudi Arabia
*
Author to whom correspondence should be addressed.
Pharmacy 2024, 12(5), 147; https://doi.org/10.3390/pharmacy12050147
Submission received: 8 August 2024 / Revised: 23 September 2024 / Accepted: 25 September 2024 / Published: 26 September 2024
(This article belongs to the Special Issue Innovations in Clinical Pharmacy: Towards Optimized Patient Care)

Abstract

:
Background: Obesity is considered a health issue associated with increased morbidity and a risk factor for multiple conditions, such as type 2 diabetes, cardiovascular diseases and infections. It may affect the pharmacokinetics and pharmacodynamics of many drugs, including antimicrobials like ciprofloxacin. Regrettably, data on ciprofloxacin’s efficacy in obese patients remain scarce. This study aims to evaluate the impact of obesity on the efficacy of ciprofloxacin in treating Gram-negative bacterial infections. Methods: A retrospective multicenter cohort study was conducted in two tertiary hospitals in Saudi Arabia. Adult patients (≥18 years) treated with ciprofloxacin for confirmed Gram-negative infection between January 2017 and April 2023 were included. Patients were excluded if they received ciprofloxacin empirically, had inadequate source control within 72 h, or had missing weight and height information at ciprofloxacin initiation. The primary outcome was clinical cure, defined as the resolution of the clinical infection manifestations without additional therapeutic management by the end of treatment. Other secondary and safety outcomes were also assessed. Results: A total of 99 patients were included, divided into obese (n = 42) and non-obese (n = 57) groups. The obese group had a significantly lower median age (50 years) compared to the non-obese group (64 years) (p = 0.002). The obese group had fewer male patients (38.10% vs. 68.42%; p = 0.004), higher body weight (90 (81–97) vs. 63 (55–70) days; p < 0.001), and lower height (158 (155–165) vs. 165 (158–172) days; p = 0.008) compared to non-obese. Urinary tract infection was the most common type, with Escherichia coli being the most common isolate. The median hospital length of stay was shorter in the obese group than in the non-obese group (1 vs. 3 days, p = 0.007). There were no significant differences in clinical cure rates between obese (85.71%) and non-obese (85.96%) patients (p = 1). No significant differences were observed in terms of in-hospital mortality, 30-day mortality, or 60-day infection recurrence rates between the two groups. Microbiological eradication was not achieved in the obese group, whereas a 10.53% eradication rate was observed in the non-obese group (p = 0.037). However, the majority of the patients had indeterminate eradication. The incidence of adverse drug reactions (ADRs) was lower in the obese group (4.76%) compared to the non-obese group (17.54%, p = 0.066). Conclusions: Treatment with ciprofloxacin in obese patients has similar efficacy and safety outcomes compared to non-obese patients with infections due to Gram-negative pathogens.

1. Introduction

Obesity is a serious disease and a significant cause of illness and death. It increases the likelihood of developing type 2 diabetes, recurrent thromboembolism, atrial fibrillation, acute coronary syndrome, and infection [1]. By 2030, more than half of the general population will be obese, and more than 10% will have morbid obesity [2]. Nonetheless, the changed physiology of obesity may have substantial implications on the pharmacokinetics and pharmacodynamics (PK/PD) of antimicrobials, sufficient to require adjustments to dosage regimens. Specifically, increases in volume distribution (Vd) are often reported in obese individuals as a consequence of increased adipose and lean muscle mass [3].
Ciprofloxacin, one of the fluoroquinolones antibiotics, is considered lipophilic in nature, plays a vital role due to its permeability through cell membranes and impacts the drug activity in the human body [4]. The data on ciprofloxacin pharmacokinetics in obesity are contradictory. When healthy volunteers (mean BMI 19.8 kg/m2) and obese volunteers (mean BMI 41.0 kg/m2) were given the same IV dose, Hollenstein et al. found no difference in Vd or CL [5]. However, one study showed increased Vd and CL (mean obese BMI 36.4 ± 3.9 kg/m2; mean control BMI 23.3 ± 2.4 kg/m2) [6]. A recent pharmacokinetics study looked at 20 morbidly obese patients (median BMI 45.8 kg/m2) and 8 non-obese patients (median BMI 21.42 kg/m2), who received one to two doses of ciprofloxacin by IV and oral routes, and they found that body weight did not affect ciprofloxacin bioavailability, CL, or Vd [7]. Dosing in continuous renal replacement therapies (CRRT) was tested in 11 critically ill septic patients using Monte Carlo simulations. They studied different ciprofloxacin dosing regimens on multiple patients’ weight groups (50 kg, 90 kg and 140 kg). The results showed that the maximum dose of 400 mg every 8 h is most likely to meet pharmacodynamic goals in patients with higher body weight and suspected hard-to-treat pathogens [8].
Because drug approval regulatory authorities do not mandate specific trials to assess therapeutic products in obese patients, there are a lack of data regarding the clinical efficacy and safety of ciprofloxacin in this population. As a result, clinicians are increasingly faced with the dilemma of using ciprofloxacin in obese patients [9].
Given the information above, it seems that ciprofloxacin doses for obese patients may be inadequate. The purpose of this study was to evaluate the impact of obesity on the efficacy and safety of ciprofloxacin for treating Gram-negative bacterial infections.

2. Materials and Methods

2.1. Study Design and Setting

This retrospective multicenter cohort study was conducted among two tertiary hospitals in Saudi Arabia, specifically at the National Guard Health Affairs medical cities in Jeddah and Riyadh. The study aimed to compare the impact of obesity on ciprofloxacin efficacy in obese versus non-obese patients infected by Gram-negative bacterial infections. The study period was from January 2017 to April 2023.

2.2. Inclusion and Exclusion Criteria

The study included all adult patients (≥18 years) who received ciprofloxacin as an inpatient for a minimum of 72 h and had isolated cultures confirming Gram-negative infections. Patients were excluded if they received ciprofloxacin empirically, lacked source control within 72 h, received ciprofloxacin as prophylaxis or had missing weight and height documentation within 72 h before or after ciprofloxacin initiation.

2.3. Sample Size and Data Collection

The initial cohort consisted of 1648 patients who were admitted to the hospital and received ciprofloxacin. After applying the exclusion criteria, 1549 patients were excluded, leaving a study cohort of 99 patients, divided into obese (n = 42) and non-obese (n = 57) groups (Figure 1). Data were extracted from electronic health records, encompassing demographics, baseline characteristics, comorbidities, severity of illness, infectious diseases consultation, relevant laboratory values, type of infection, concurrent and previous antibiotic use, microbiological and susceptibility data, and other concurrent infections. Clinical cure was assessed through a review of progress notes documented by treating clinicians, vital signs, laboratory data, and radiographic findings. The clinical cure was further evaluated by a specialized clinical pharmacist in infectious diseases. Safety outcomes were assessed by using the RIFLE criteria for renal function and the documentation of ADRs in the primary physician notes.

2.4. Key Definitions Used in the Study

Clinical cure was defined as the resolution of clinical manifestations associated with the infection, confirmed by the absence of the need for additional therapeutic management for Gram-negative infections due to failure or adverse effects by the end of therapy. Time to study drug was defined as the number of hours from the collection of the first index cultures to the initiation of ciprofloxacin. In-hospital mortality was defined as death occurring for any reason during the hospital admission. Thirty-day mortality was defined as death occurring within 30 days of the initiation of ciprofloxacin, and considered infection-related if patients had ongoing clear clinical or biochemical signs of infection at the time of their death. Microbiological eradication was defined as the negative result of the repeated culture from the site of infection. The polymicrobial infection was defined as the presence of at least one additional pathogenic microorganism during the same episode of the index infection. Sixty-day infection recurrence was defined as the presence of clinical signs and symptoms of infection with repeated isolation of the same pathogen within 60 days of the primary infection episode. Obesity was defined as a body mass index (BMI) of ≥30.

2.5. Microbiologic Testing

In this retrospective study, susceptibility results of bacterial isolates were obtained from samples previously collected during routine clinical care at our institutions. Only Gram-negative bacterial isolates confirmed to be susceptible to ciprofloxacin, using the VITEK® MS MALDI-TOF and VITEK® 2 systems (bioMérieux, Marcy-l’Étoile, France), were included.

2.6. Statistical Analysis

Categorical variables were expressed as numbers and percentages and compared using the chi-square test or Fisher’s exact test. Continuous variables were presented as median and interquartile range (IQR) and compared using the Mann–Whitney U test. A multivariate logistic regression model was used to identify the predictors of clinical cure events. Covariates were identified through clinical considerations and relevant baseline clinical characteristics associated with a p value < 0.1 in the univariate analysis. To prevent multicollinearity, the variance inflation factor (VIF) was calculated for every variable included and considered acceptable if VIF values were <5. Model discrimination was assessed with the area under the receiver operating characteristic curve (AUC), and model calibration was assessed with the Hosmer–Lemeshow test. Statistical results were considered significant using a two-tailed p value of less than 0.05. All statistical analyses were performed using SPSS software version 26.0 (IBM, Chicago, IL, USA).

3. Results

The study included 99 patients, of whom 42 were obese (BMI ≥ 30) and 57 were non-obese (BMI < 30). The median age in the obese group was significantly lower at 50 years compared to the non-obese group at 64 years (p = 0.002). The distribution by gender, height, and actual weight was significantly different between groups, with obese patients characterized by fewer male patients (38.10% vs. 68.42%; p = 0.004), a higher median body weight of 90 (81–97) vs. 63 (55–70) days (p < 0.001), and a lower median height of 158 (155–165) vs. 165 (158–172) days (p = 0.008) than those who are not obese. Baseline serum creatinine levels and the prevalence of most comorbid conditions did not differ significantly, although the Charlson comorbidity index was higher in non-obese patients (median 4 vs. 2, p = 0.001). Most of the infections were due to urinary tract infection (UTI), which accounted for 69.05% and 57.89% of the cases in obese and non-obese patients, respectively. Other sources of infection included osteomyelitis, intra-abdominal infections, and acute bacterial skin and skin structure infections. The isolates most commonly found included Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The type distribution of infections and causative pathogens revealed no significant difference between the obese and non-obese groups. More information is detailed in Table 1.
Clinical cure at end of treatment was also similar; 85.71% of the obese were clinically cured, and 85.96% of the non-obese were clinically cured (p = 1). Microbiological eradication was not achieved in any of the obese patients, compared to 10.53% eradication in non-obese patients (p = 0.037). However, most of the patients in both groups were indeterminate about microbiological eradication. When comparing the two groups, no statistically significant difference was observed in overall hospital mortality (7.02% vs. 2.38%; p = 0.392). Similarly, 30-day all-cause mortality and 30-day and 60-day recurrence rates did not differ significantly between the two groups. The length of stay of hospitalization from the initiation of ciprofloxacin to discharge was significantly shorter in obese patients compared to non-obese patients (median = 1 vs. 3 days; p = 0.007). ADRs were less reported in the current study, with a prevalence of 4.76% in obese patients and 17.54% in non-obese patients (p = 0.066). The incidence of acute kidney injury, Clostridioides difficile infection, hepatotoxicity, nausea and vomiting, seizures, and thrombocytopenia did not significantly differ between the two groups. None of the obese group discontinued ciprofloxacin due to ADRs, while 1.75% of non-obese patients discontinued treatment due to adverse events (Table 2). The relationship between different clinical factors and incidence of clinical cure was evaluated using multivariate logistic regression analysis. The concurrent antibiotic use, lymphoma, overall duration of hospital stay, time to administration of study drug and antibiotic used prior to ciprofloxacin with activity against the isolated organism met the enrollment criteria for the multivariate logistic regression model. However, the multivariate analysis showed that none of these factors remained significantly associated with clinical cure events when adjusted for other variables (Table 3).

4. Discussion

According to our knowledge, this is the first study to specifically compare the clinical efficacy of ciprofloxacin between obese and non-obese patients. The findings of this study showed that ciprofloxacin is equally effective at achieving clinical cure in obese and non-obese groups. Moreover, there were no significant differences regarding mortality rates or recurrence of infection. While contrasting these results, Longo et al. reported that obesity was a significant predictor of antibiotic treatment failure, potentially leading to higher recurrence rates [10]. Moreover, Barber and his colleagues reported higher rates of treatment failures in obese patients treated with ceftriaxone therapy compared to non-obese patients [11]. This difference could be due to variations in study design, population characteristics, or infection management protocols, highlighting the need for further prospective studies to clarify these findings.
Van Rhee et al. also reported that the pharmacokinetics of ciprofloxacin were not significantly influenced in obese patients; its therapeutic effectiveness could be successfully preserved with appropriate dose adjustments. This suggests that ciprofloxacin can be effectively used across different BMI categories with careful monitoring and dosage adjustments without compromising clinical outcomes [7]. However, another study conducted by Allard et al. found that ciprofloxacin clearance is significantly higher in obese patients, necessitating higher doses to achieve therapeutic levels [6]. In this current study, we could not assess the impact of different doses on the clinical cure as a larger sample size is needed. However, the median doses of ciprofloxacin were not significantly different between the two groups.
A unique finding in the current study is the shorter hospital length of stay observed in obese patients (median 1 day) compared to non-obese patients (median 3 days). This finding diverges from the general expectation that obese patients might require longer hospitalizations due to complications related to both obesity and infection management [12]. This shorter length of stay could be attributed to another hypothesis, which is that obese patients in the current study started on ciprofloxacin when they were stable and ready for discharge, highlighting an area for further investigation. Moreover, UTI was the most common infection in both groups, as it is mostly caused by Gram-negative organisms and ciprofloxacin is the preferred oral agent to discharge the patients on it.
In terms of safety, the present study reported a lower occurrence of ADRs among obese patients (4.76%), compared to 17.54% in non-obese patients. The current study is in disagreement with Modesto et al., who reported that one-third of their included obese patients experienced ADRs, which highlights the importance of careful medication management in obese patients due to their susceptibility to ADRs driven by complex therapeutic regimens and multiple health conditions [13]. It is worth mentioning that this variation may be due to the criteria used for documenting ADRs in our study or a difference in individual responses to ciprofloxacin.
Our study found no microbiological eradication in obese patients compared to a 10.53% eradication rate in non-obese patients. The lower eradication rates observed might be attributed to several factors, including difficulty ensuring sufficient ciprofloxacin tissue concentrations in the obese. Studies such as those by Hollenstein et al. and Alobaid et al. have highlighted the difficulties associated with achieving adequate drug levels within adipose tissues [3,4,5]. Regrettably, no available studies that examined the influence of obesity on bacterial eradication were identified in the literature. Nevertheless, the current study finding should be interpreted with caution as the majority of the patients had an indeterminate eradication outcome.
Our study has several limitations. The retrospective design may introduce selection bias and potential confounding factors not accounted for in the analysis. The relatively small sample size of obese patients limits the generalizability of the findings. Additionally, the study did not account for variations in ciprofloxacin dosing regimens or adherence to treatment protocols, which could influence the outcomes. Different sources of infection may create heterogeneity in the results of the study. Data on specific MICs were not documented; however, we only included cases with identified and susceptible pathogens to ciprofloxacin. We rely on physician notes regarding the incidence of ADR, which may underestimate the incidence of ADR between two groups. Finally, most of the patients in both groups have indeterminate microbiological eradication, which might explain the lower documented eradication rates observed in the current study.

5. Conclusions

This study showed that ciprofloxacin efficacy and safety in treatment of Gram-negative infections were not statistically different between obese and non-obese patient study groups. Only length of hospital stay outcome was lower in obese group.

Author Contributions

Conceptualization, S.A. (Sultan Alotaibi), N.D. and A.A. (Abdullah Alqurashi); methodology, S.A. (Sultan Alotaibi), A.A. (Ahmed Alnefaie) and S.A. (Sami Althagafi); software, A.A. (Abdullah Alsuwat) and M.A.; validation, N.D., S.A. (Sultan Alotaibi) and A.A. (Aown Alotaibi); formal analysis, S.A. (Sultan Alotaibi ); investigation, A.A. (Ahmed Alnefaie), S.A. (Sultan Alotaibi) and A.A. (Abdullah Alqurashi); data curation, N.D.; writing—original draft preparation, S.A. (Sultan Alotaibi), A.A. (Aown Alotaibi) and S.A. (Sami Althagafi); writing—review and editing, N.D., S.A. (Sultan Alotaibi) and A.A. (Abdullah Alsuwat); supervision, N.D.; project administration, S.A. (Sultan Alotaibi). All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was approved by the Institutional Review Board of King Abdullah International Medical Research Center (KAIMRC) (study number NRJ/23J/075/03, approval date: 11 June 2023).

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this study are available on request from the corresponding author due to privacy.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Falagas, M.E.; Athanasoulia, A.P.; Peppas, G.; Karageorgopoulos, D.E. Effect of body mass index on the outcome of infections: A systematic review. Obes. Rev. 2009, 10, 280–289. [Google Scholar] [CrossRef] [PubMed]
  2. Kelly, T.; Yang, W.; Chen, C.S.; Reynolds, K.; He, J. Global burden of obesity in 2005 and projections to 2030. Int. J. Obes. 2008, 32, 1431–1437. [Google Scholar] [CrossRef] [PubMed]
  3. Alobaid, A.S.; Hites, M.; Lipman, J.; Taccone, F.S.; Roberts, J.A. Effect of obesity on the pharmacokinetics of antimicrobials in critically ill patients: A structured review. Int. J. Antimicrob. Agents 2016, 47, 259–268. [Google Scholar] [CrossRef] [PubMed]
  4. Czyrski, A. The spectrophotometric determination of lipophilicity and dissociation constants of ciprofloxacin and levofloxacin. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2022, 265, 120343. [Google Scholar] [CrossRef] [PubMed]
  5. Hollenstein, U.M.; Brunner, M.; Schmid, R.; Müller, M. Soft tissue concentrations of ciprofloxacin in obese and lean subjects following weight-adjusted dosing. Int. J. Obes. 2001, 25, 354–358. [Google Scholar] [CrossRef] [PubMed]
  6. Allard, S.; Kinzig, M.; Boivin, G.; Sörgel, F.; Lebel, M. Intravenous ciprofloxacin disposition in obesity. Clin. Pharmacol. Ther. 1993, 54, 368–373. [Google Scholar] [CrossRef] [PubMed]
  7. Van Rhee, K.P.; Smit, C.; Wasmann, R.E.; van der Linden, P.D.; Wiezer, R.; Van Dongen, E.P.; Krekels, E.H.; Brüggemann, R.J.; Knibbe, C.A. Ciprofloxacin pharmacokinetics after oral and intravenous administration in (morbidly) obese and non-obese individuals: A prospective clinical study. Clin. Pharmacokinet. 2022, 61, 1167–1175. [Google Scholar] [CrossRef] [PubMed]
  8. Roger, C.; Wallis, S.C.; Louart, B.; Lefrant, J.Y.; Lipman, J.; Muller, L.; Roberts, J.A. Comparison of equal doses of continuous venovenous haemofiltration and haemodiafiltration on ciprofloxacin population pharmacokinetics in critically ill patients. J. Antimicrob. Chemother. 2016, 71, 1643–1650. [Google Scholar] [CrossRef] [PubMed]
  9. Jacques, K.A.; Erstad, B.L. Availability of information for dosing injectable medications in underweight or obese patients. Am. J. Health-Syst. Pharm. 2010, 67, 1948–1950. [Google Scholar] [CrossRef] [PubMed]
  10. Longo, C.; Bartlett, G.; MacGibbon, B.; Mayo, N.; Rosenberg, E.; Nadeau, L.; Daskalopoulou, S.S. The effect of obesity on antibiotic treatment failure: A historical cohort study. Pharmacoepidemiol. Drug Saf. 2013, 22, 970–976. [Google Scholar] [CrossRef] [PubMed]
  11. Barber, K.E.; Loper, J.T.; Morrison, A.R.; Stover, K.R.; Wagner, J.L. Impact of obesity on ceftriaxone efficacy. Diseases 2020, 8, 27. [Google Scholar] [CrossRef] [PubMed]
  12. Huttunen, R.; Syrjänen, J. Obesity and the risk and outcome of infection. Int. J. Obes. 2013, 37, 333–340. [Google Scholar] [CrossRef] [PubMed]
  13. Modesto, A.C.; Silveira, E.A.; Santos, A.S.; Rodrigues, A.P.; Lima, D.M.; Provin, M.P.; Amaral, R.G. Prevalence of adverse drug events in severely obese adults and associated factors: Clinical trial baseline results. Sci. Pharm. 2020, 88, 41. [Google Scholar] [CrossRef]
Figure 1. Patient enrollment and screening for eligibility.
Figure 1. Patient enrollment and screening for eligibility.
Pharmacy 12 00147 g001
Table 1. Patient demographic and clinical characteristics.
Table 1. Patient demographic and clinical characteristics.
CharacteristicNon-Obese (n = 57)Obese (n = 42)p-Value
Age (years)64 (52–74)50 (39–63)0.002
Male n (%)39 (68.42%)16 (38.10%)0.004
Height (cm)165 (158–172)158 (155–165)0.008
Actual Body Weight (kg)63 (55–70)90 (81–97)<0.001
Baseline Scr (µmol/L)72 (58–103)68 (58–79)0.129
Comorbidity, n (%)
 Cerebrovascular disease5 (8.77)1 (2.38)0.237
 Chronic heart failure7 (12.28)1 (2.38)0.133
 Chronic obstructive pulmonary disease2 (3.51)1 (2.38)1
 Dementia4 (7.02%)1 (2.38)0.392
 Diabetes mellitus28 (49.12)20 (47.62)0.882
 Hemiplegia or paraplegia1 (1.75)0 (0%)1
 Hypertension27 (47.37)11 (26.19)0.22
 Liver disease6 (10.53)2 (4.76)0.461
 Lymphoma2 (3.51)2 (4.76%)1
 Leukemia3 (5.26%)0 (0%)1
 Moderate to severe chronic renal failure8 (14.04)3 (7.14)0.346
 Neurological disease6 (85.71)1 (2.38)0.233
 Peripheral vascular disease2 (3.51)1 (2.38)1
 Solid Tumor8 (14.04)6 (14.29%)0.971
Charlson comorbidity index 4 (2–6) 2 (0.25–4) 0.001
Immunosuppression, n (%)10 (17.54%)7 (16.67%)0.909
 Active chemotherapy8 (80%)5 (71.43%)
 Neutropenia (ANC < 500)1 (10%)1 (14.29%)
 Solid Organ Bone Marrow Transplant1 (10%)1 (14.29%)
Type of infection, n (%)
 Acute Bacterial Skin and Skin Structure Infections3 (5.26%)2 (4.76%)1
 Intra-abdominal Infections5 (8.77%)4 (9.52%)1
 Osteomyelitis6 (10.53%)3 (7.14%)0.729
 Urinary Tract Infections33 (57.89%)29 (69.05%)0.257
 Other14 (24.56%)5 (11.90%)0.114
Causative Pathogen, n (%)
 Enterobacter cloacae6 (10.53%)3 (7.14%)0.729
 Escherichia coli24 (42.11%)23 (54.76%)0.212
 Klebsiella pneumoniae11 (19.30%)9 (21.43%)0.794
 Pseudomonas aeruginosa12 (21.05%)6 (14.29%)0.388
 Other pathogens (combined)4 (7.02%)3 (7.14%)1
Concurrent Polymicrobial Infections, n (%)5 (8.77%)1 (2.38%)0.237
 Enterococcus faecium1 (20%)0 (0%)
 Klebsiella pneumoniae2 (40%)0 (0%)
 Methicillin-resistant Staphylococcus aureus2 (40%)1 (100%)
Presence of Bacteremia, n (%)6 (10.53%)3 (7.14%)0.729
Antibiotic Used Before Ciprofloxacin with activity against the isolated organism in the same course, n (%)25 (43.86%)11 (26.19%)0.071
Time to Study Drug (hours)36 (24–72)30 (24–47)0.249
Total Daily Dose in mg (e.g., 1000)1000 (800–1000)1000 (1000–1000)0.198
Concurrent antibiotic for more than 48 h with in vitro activity against the causative pathogen, n (%)5 (8.77%)1 (2.38%)0.237
Duration of Treatment (days)7 (7–10)7 (7–10)0.949
Overall Duration of Hospitalization (days)9 (4–16)6 (2–12)0.121
ICU Admission at Infection Onset, n (%)1 (1.75%)2 (4.76%)0.573
Septic shock, n (%)1 (1.75%)1 (2.38%)1
Mechanical Ventilation, n (%)2 (3.51%)1 (2.38%)1
Infectious Disease Consultation, n (%)10 (17.54%)5 (11.90%)0.439
Table 2. Study outcomes.
Table 2. Study outcomes.
OutcomesNon-Obese (n = 57)Obese (n = 42)p-Value
Clinical cure by End of Treatment49 (85.96%)36 (85.71%)1
Microbiological outcome
 Persistent Infection5 (8.77%)3 (7.14%)1
 Eradication6 (10.53%)0 (0%)0.037
 Indeterminate46 (80.7%)39 (92.86%)0.086
Overall In-Hospital Mortality4 (7.02%)1 (2.38%)0.392
30-day All-Cause Mortality2 (3.51%)1 (2.38%)1
Infection-Related Mortality1 (1.75%)1 (2.38%)1
60-day Recurrence2 (3.51%)3 (7.14%)0.447
Hospital LOS from Start of Ciprofloxacin to Discharge (days)3 (1–9)1 (1–2)0.007
Adverse Drug Reaction10 (17.54%)2 (4.76%)0.066
 Acute Kidney Injury3 (5.26%)1 (2.38%)
Clostridioides difficile Infection2 (3.51%)0 (0%)
 Hepatotoxicity2 (3.51%)0 (0%)
 Nausea and vomiting0 (0%)1 (2.38%)
 Seizure2 (3.51%)0 (0%)
 Thrombocytopenia1 (1.75%)0 (0%)
Discontinuation Due to Adverse Event1 (1.75%)0 (0%)1
Table 3. Multivariate logistic regression analysis with clinical cure events as dependent variable a.
Table 3. Multivariate logistic regression analysis with clinical cure events as dependent variable a.
VariableUnivariateMultivariate
OR (95% CI)p-ValueOR (95% CI)p-Value
Concurrent antibiotic for more than 48 h0.13 ([0.02–0.74])0.0220.34 ([0.05–2.41])0.279
Lymphoma0.38 ([0.13–1.06])0.0640.10 ([0.01–1.12])0.062
Overall duration of hospitalization0.98 ([0.96–1.00])0.0910.98 ([0.96–1])0.053
Time to Study Drug0.99 ([0.98–0.99])0.0461.00 ([0.99–1])0.359
Antibiotic Used Before Ciprofloxacin with activity0.17 ([0.05–0.61])0.0060.26 ([0.06–1.17]) 0.079
Abbreviations: OR, odds ratio; CI, confidence interval. a Discrimination (AUC = 0.783) and calibration (Hosmer and Lemeshow χ2 = 5.722; p = 0.678).
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Alotaibi, S.; Damfu, N.; Alnefaie, A.; Alqurashi, A.; Althagafi, S.; Alotaibi, A.; Alotaibi, M.; Alsuwat, A. Efficacy of Ciprofloxacin in Treating Gram-Negative Infections: Does Obesity Matter? Pharmacy 2024, 12, 147. https://doi.org/10.3390/pharmacy12050147

AMA Style

Alotaibi S, Damfu N, Alnefaie A, Alqurashi A, Althagafi S, Alotaibi A, Alotaibi M, Alsuwat A. Efficacy of Ciprofloxacin in Treating Gram-Negative Infections: Does Obesity Matter? Pharmacy. 2024; 12(5):147. https://doi.org/10.3390/pharmacy12050147

Chicago/Turabian Style

Alotaibi, Sultan, Nader Damfu, Ahmed Alnefaie, Abdullah Alqurashi, Sami Althagafi, Aown Alotaibi, Musim Alotaibi, and Abdullah Alsuwat. 2024. "Efficacy of Ciprofloxacin in Treating Gram-Negative Infections: Does Obesity Matter?" Pharmacy 12, no. 5: 147. https://doi.org/10.3390/pharmacy12050147

APA Style

Alotaibi, S., Damfu, N., Alnefaie, A., Alqurashi, A., Althagafi, S., Alotaibi, A., Alotaibi, M., & Alsuwat, A. (2024). Efficacy of Ciprofloxacin in Treating Gram-Negative Infections: Does Obesity Matter? Pharmacy, 12(5), 147. https://doi.org/10.3390/pharmacy12050147

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop