Pharmacoeconomic Evaluation of Once-Daily Aminoglycoside Treatment

Abstract

A special topic in pharmacoeconomics concerns antimicrobial therapy. The cost of antimicrobial therapy and an economic evaluation of aminoglycoside antibiotics in the last 30 years are reviewed. Some innovative approaches have been found to be effective in the control of the use of aminoglycosides and those are: 1) selecting the appropriate aminoglycoside, 2) therapeutic drug monitoring and, 3) once-daily administration. The practical advantages of once-daily aminoglycoside dosing are discussed and the conclusion is that combination therapy continues to be a mainstay in several serious Gram-negative infections.

Concerns about breakthrough infection with extended aminoglycoside dosing intervals can be resolved by combination with a betalactam antibiotic. The lower costs associated with once-daily aminoglycoside dosing are the consequence of a straightforward dosage calculation, a guaranteed peak serum concentration in the therapeutic range, potential reduction in treatment period, easier quality control of preparation and administration, decreased personnel time, and fewer assays. However, some practical considerations remain unanswered.     

Cost-effectiveness of Intensity-modulated Radiotherapy in Prostate Cancer

AimsTo compare the costs and effectiveness of intensity-modulated radiotherapy (IMRT) with three-dimensional conformal radiotherapy (3DCRT) for the radical treatment of localised prostate cancer at elevated doses (>70 Gy).Materials and methodsA cost-effectiveness analysis model was developed using clinical effectiveness estimates from a systematic review. The base case analysis assumes equal biochemical survival for IMRT and 3DCRT, but lower frequency of gastrointestinal toxicity for IMRT. The costs of IMRT and 3DCRT were estimated through activity-based costing, incorporating input from radiation oncologists, physicists and treatment planners.ResultsThe delivery of IMRT produced 0.023 more quality-adjusted life-years (QALY) than 3DCRT at an additional cost of $621 (QALY and costs discounted at 5% per year), yielding an incremental cost-effectiveness ratio of $26 768 per QALY gained. The treatment cost of IMRT was $1019 more than 3DCRT, but IMRT resulted in less frequent gastrointestinal toxicity, thus avoiding $402 in the treatment of toxicity. In the scenario that compared a higher dose of IMRT (75.6 Gy) to 3DCRT (68.4 Gy), IMRT improved disease control with equal toxicity incidence, and the IMRT strategy dominated (less costly and more effective). In the base case scenario (no survival difference), the cost-effectiveness of IMRT was most sensitive to the treatment cost difference between IMRT and 3DCRT.ConclusionFor radical radiation treatment (>70 Gy) of prostate cancer, IMRT seems to be cost-effective when compared with an equivalent dose of 3DCRT.     

Effect of a Policy for Restriction of Selected Classes of Antibiotics on Antimicrobial Drug Cost and Resistance

Abstract

Based on the instructions of the National Organization of Pharmaceutical Agents (Greece) from July 1, 2003, quinolones, 3^rd and 4^th generation cephalosporins, carbapenems, monobactams, glycopeptides, oxazolidinones, and streptogramins were considered as “restricted” antibiotics that could be used only with the approval of an Infectious Disease specialist. We analyzed the effect of the policy on the consumption and cost of antibiotics as a group and of specific classes, adjusted for the patient load, as well as on the antimicrobial resistance of isolated bacteria. We analyzed 5 trimesters (2 prior and 3 after the implementation of the new policy). A 20% and 16% reduction in adjusted consumption [in daily defined doses (DDDs)] and cost, respectively, of the restricted antibiotics was accomplished during the first trimester after implementation of the new policy. However, this was accompanied by a 36% and 56% increase in adjusted consumption and cost, respectively, of unrestricted antibiotics. A logistic regression model that we performed showed that the new policy had an independent positive effect on the in vitro antimicrobial susceptibility of Pseudomonas aeruginosa (p=0.051) but not of Acinetobacter baumannii and Escherichia coli isolates. Our data suggest that there are considerable limitations to the programs aiming to reduce the consumption of restricted antibiotics through the approval of their use by specialists, at least in some settings.     

Antimicrobial Prophylaxis in Surgery: The Role of Pharmacokinetics

Abstract

Even though surgical infection rates have decreased dramatically during the past 25 years, morbidity and mortality of infection in surgical treatment remains substantial. From a pharmacologycal point of view, the key factor of the efficacy of antibiotic prophylaxis is to attain bactericidal levels of antibiotic in serum and tissues (target site) during the whole intraoperative and early postoperative period. The success of antibiotic prophylaxis is assured only when the chosen antibiotic with a targeted spectrum and high antimicrobial efficacy is available at the critical moment, at the correct site and in sufficiently high concentration to prevent bacterial contamination of the surgical area. It would be desirable for reasons of convenience and cost if a single preoperative administration were sufficient. The pharmacokinetics and the half-life of antibiotics in the serum are directly related to the duration of activity of antibiotic in the tissue. Antibiotics with longer half-lives maintain levels in the tissues for longer periods than do antibiotics with shorter half-lives and they cover with a single dose the time required for prophylaxis even for longer operations. Finally, the application of the pharmacokinetic properties of antibiotics to surgical prophylaxis can provide the surgeon with certainty that adequate coverage and protection with antibiotics are achieved before and throughout the operation.     

Point prevalence survey on antibiotic use in a Croatian Infectious Disease Hospital

Abstract

Antibiotic use is the driving force for increasing antibiotic resistance. A large proportion of antibiotics in hospitals are used inadequately. The objective of this study was to evaluate antibiotic use at the Hospital for Infectious Diseases through point-prevalence surveys conducted in 2006, 2008, and 2009. Point prevalence surveys were part of the European Surveillance on Antimicrobial Consumption (ESAC) Hospital Care Subproject and patients’ data were collected following ESAC protocol. Additionally, the adequacy of antimicrobial therapy and administration of the first line antibiotic according to the local guidelines were assessed by an infectious disease doctor and a clinical microbiologist. In the study period among the 599 patients admitted to hospital, 352 (58·8%) received antibiotics. Out of 448 antimicrobial treatments, 313 (69·9%) were administered parenterally and 135 (30·1%) orally. Altogether in years 2006, 2008, and 2009 the most commonly prescribed antibiotics were ceftriaxone (19·9%), co-amoxiclav (15·4%), ciprofloxacin (12·3%), narrow spectrum penicillins (6·5%), and penicillinase resistant penicillins (5·6%). Most (82·6%) of the treated infections were community acquired infections. The predominating diagnoses were urinary tract infections and infections with no primary site defined, followed by skin, soft tissue and bone and joint infections. The overall adequacy of antimicrobial therapy was 82% and the first line antibiotic according to the local guidelines was administered with high frequency for central nervous system and cardiovascular infections (100%), and low for ear, nose, and throat infections, urinary tract infections, lower respiratory tract and bone and joint infections (23·0%, 51·6%, 52·5%, 65·0%, respectively) which indicates a significant overuse of antibiotics for diagnoses listed. The results of an individual point prevalence survey provided reliable and representative data for the hospital. Point-prevalence surveys proved to be a valuable method for detecting targets for antibiotic prescribing improvement and they clearly showed that our local hospital guidelines offered too many choices of antibiotic treatment for each clinical indication and needed revision.     

Antibiotic Lock-Technique for the Treatment of Catheter-Related Bloodstream Infections

Abstract

The management of central venous catheter-related bloodstream infections (CRBSI), though still debated, requires the removal of the line in most cases: we investigated the efficacy of an alternative approach, based on higher concentrations of antibiotics locked within the catheter lumen, in an open, pilot study aimed at preserving the line in place and at eradicating the infection.

Thirty consecutive patients carrying a central line over 10 days and who fulfilled criteria for ascertained diagnosis of bacterial CRBSI, had the catheter “locked” with antimicrobials therein; all patients also received systemic antibiotic therapy within the first 48 hours. Subsequently, 15 patients underwent locks alone, and 15 locks plus systemic therapy. Twenty-eight out of 30 (93.3%) patients retained the catheter in place, appearing to be cleared of infection and no treatment-related untoward events were observed.

Locks should be considered as effective as line removal in the management of bacterial CRBSI in unselected patients, and could thus provide advantages in terms of resource sparing and lowered antibiotic pressure in the hospital setting.     

Evidence on the economic value of psychosocial interventions to alleviate anxiety and depression among cancer survivors: a systematic review

Aim: With cancer cases expected to rise in the coming decades, increased demands will be placed on our health system to address the psychosocial care of patients affected by cancer. The objective of this study was to review the evidence on the cost effectiveness of psychological interventions for individuals with cancer. Methods: A systematic review was undertaken to assess the cost effectiveness of psychosocial approaches specifically treating depression or anxiety, or both, in patients with cancer. Major medical databases were searched together with reference lists from eligible articles. A narrative approach was used to synthesise the findings and quality assessment was guided by recommendations by Drummond's 10‐point checklist for reporting health economic evaluations. Results: The review yielded five cost‐effectiveness studies. Most interventions showed improvements in some psychological outcomes. Three studies reported slightly but not significantly higher health‐care costs for their intervention than their comparison groups. Costs of the interventions ranged from US$47 to $629 per patient. One study of patients with mixed cancer diagnoses used the preferred outcome “quality‐adjusted life years” (QALY) and found a cost‐effective investment for an intensive nurse‐led program with reported incremental costs of £5278 per QALY gained. No study undertook a comprehensive sensitivity analysis although two studies performed simple one‐way sensitivity analyses. Conclusion: Current results are inconclusive due to study heterogeneity and inadequate analyses but suggest that psychosocial interventions are inexpensive on a per patient basis. Future studies should routinely include preference‐based utility instruments to capture psychological distress in economic evaluation.     

Quality of life assumptions determine which cervical cancer screening strategies are cost‐effective

Quality‐adjusted life years are used in cost‐effectiveness analyses (CEAs). To calculate QALYs, a “utility” (0–1) is used for each health state induced or prevented by the intervention. We aimed to estimate the impact of quality of life (QoL) assumptions (utilities and durations of health states) on CEAs of cervical cancer screening. To do so, 12 alternative sets of utility assumptions were retrieved from published cervical cancer screening CEAs. Two additional sets were based on empirical QoL data that were integrally obtained through two different measures (SF‐6D and EQ‐5D) from eight groups of women (total n = 3,087), from invitation for screening to diagnosis with cervical cancer. Per utility set we calculated the number of quality‐adjusted days lost (QADL) for each relevant health state in cervical cancer screening, by multiplying the study‐specific assumed disutilities (i.e., 1‐utility) with study‐specific durations of the loss in QoL, resulting in 14 “QADL‐sets.” With microsimulation model MISCAN we calculated cost‐effectiveness of 342 alternative screening programs (varying in primary screening test [Human Papillomavirus (HPV) vs. cytology], starting ages, and screening interval) for each of the 14 QADL‐sets. Utilities used in CEAs appeared to differ largely. We found that ten QADL‐sets from the literature resulted in HPV and two in cytology as preferred primary test. The SF‐6D empirical QADL‐set resulted in cytology and the EQ‐5D one in HPV as preferred primary test. In conclusion, assumed utilities and health state durations determine cost‐effectiveness of cervical cancer screening. Also, the measure used to empirically assess utilities can be crucial for CEA conclusions.     

High-Dose Intravenous Fluoroquinolones in the Treatment of Severe Infections

Abstract

A bacterial infection should be considered “serious” in case of underlying disease, nosocomial origin, antibiotic resistant pathogen, and/or poor delivery of antibiotics at the site of infection. Treatment of most serious infections requires parenteral administration of antimicrobial agents. Intravenous fluoroquinolones are a class of antimicrobial agents from which physicians must choose when treating nosocomial infections. Fluoroquinolones are bactericidal antimicrobial agents that act by inhibiting DNA gyrase. They are active in vitro against most Gram-negative bacteria and methicillin-susceptible staphylococci. Activity against anaerobic bacteria and streptococci is poor. The rapid development of bacterial resistance in centers with high quinolone usage is of great concern. Resistance develops most commonly in Pseudomonas aeruginosa and staphylococci. Most clinical trials with ciprofloxacin, ofloxacin, pefloxacin, the fluroquinolones currently available in France for parenteral use, are almost 10 years old. There are few studies with higher dosage and most of them have been carried out with ciprofloxacin. The findings of these studies indicate that higher dosage regimens of i.v. ciprofloxacin are much more effective against severe nososcomial infections than is the dosage of 200 mg twice daily. The higher dosage regimens resulted in greater rates of clinical cure and improvement in both monomicrobial and polymicrobial infections. Although the overall frequency of side effects to fluoroquinolones is low, seizures and allergic reactions have been attributed to their use.     

Is Radiation Therapy Cost-Effective in the Positron Emission Tomography/Computed Tomography Era for Early-Stage Favorable Hodgkin Lymphoma With Alternative Payment Models?

PurposeDespite multiple randomized trials, variation in practice remains regarding the most effective treatment for early-stage, favorable-risk Hodgkin lymphoma. With increasing emphasis on alternative payment models, we investigate the cost-effectiveness of chemotherapy alone versus combined modality therapy (CMT).Methods and MaterialsA Markov model was formed to compared 2 cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) to 2 cycles of ABVD followed by 20 Gy in 10 fractions involved-site radiation therapy. Modalities were compared using the incremental cost-effectiveness ratio, with effectiveness measured in quality-adjusted life years (QALYs) and evaluated with a willingness to pay a threshold of $100,000 per QALY gained.ResultsThe base case analysis showed that CMT is cost-effective compared with ABVD alone, with an incremental cost-effectiveness ratio of $8028 per QALY gained and an incremental cost of $236 gaining 0.029 QALYs. On sensitivity analyses, the results were the most sensitive to changes in recurrence rates. If the recurrence rate differences were ≥6%, CMT was cost-effective.ConclusionsCMT is a cost-effective strategy for early-stage, favorable-risk Hodgkin lymphoma based on currently available evidence. However, small variations in recurrence-rate estimates dramatically affect strategy cost-effectiveness.     

Cost-Effectiveness of Zoledronic Acid Plus Endocrine Therapy in Premenopausal Women With Hormone-Responsive Early Breast Cancer

PurposeThe aim of this study was to estimate the cost-effectiveness of adding zoledronic acid 4 mg intravenously every 6 months to endocrine therapy in premenopausal women with hormone receptor—positive early breast cancer from a US health care system perspective.Materials and MethodsA Markov model was developed to predict disease progression, mortality, and costs of breast cancer care for premenopausal women with hormone receptor—positive early breast cancer receiving up to 3 years of (1) endocrine therapy (goserelin plus tamoxifen or anastrozole); or (2) endocrine therapy plus zoledronic acid. Model parameters were obtained from ABCSG-12 (Austrian Breast and Colorectal Cancer Study Group Trial-12) and the literature. The incremental cost per quality-adjusted life year (QALY) gained with zoledronic acid was calculated under 2 scenarios: (1) benefits of zoledronic acid persist to maximum (7 years) follow-up in ABCSG-12 (“trial benefits”) or (2) benefits persist until death (“lifetime benefits”).ResultsAdding zoledronic acid to endocrine therapy was projected to yield a gain of 0.41 life years (LYs) and 0.43 QALYs assuming trial benefits and 1.34 LYs and 1.41 QALYs assuming lifetime benefits. Assuming trial benefits, the incremental cost per QALY gained with zoledronic acid was $9300. Assuming lifetime benefits, zoledronic acid was estimated to increase QALYs and reduce costs. Cost per QALY gained was ≤ $56,000 in all deterministic sensitivity analyses and was ≤ $50,000 in 94% and 97% of probabilistic sensitivity analyses for trial and lifetime benefits scenarios, respectively.ConclusionAdding zoledronic acid to endocrine therapy in premenopausal women with hormone receptor—positive early breast cancer is cost-effective from a US health care system perspective.     

Cost-effectiveness Analysis of Innovative Therapy for Patients with Newly Diagnosed Hormone-Sensitive Metastatic Prostate Cancer

BackgroundThe optimal therapeutic strategies for patients with metastatic hormone-sensitive prostate cancer (mHSPC) followed by metastatic castrate-resistant prostate cancer (mCRPC), in terms of cost and effectiveness, remains unknown. This study aims to compare the cost-effectiveness of various potential strategies, from the start of first-line treatment in mHSPC to the death of the patients.MethodsTwo Markov decision-analysis models were developed, one for cohort A “asymptomatic/mildly symptomatic patients in mCRPC”, and one for cohort B “symptomatic patients in mCRPC”. Each strategy reflects daily practice for mHSPC until progression in mCRPC from the start of first treatment regimen with either docetaxel or abiraterone acetate plus prednisone (AA) in mHSPC to the death of the patient. The cost-effectiveness analysis was performed from the French public health care system perspective. Only direct medical costs were included. Survival data were extracted from results of published randomized clinical trials.ResultsFor cohort A, docetaxel followed by AA is the most cost-effective therapeutic strategy (€96,925 for 4.24 life-years). For cohort B, docetaxel followed by docetaxel is the most cost-effective therapeutic strategy (€81,463 for 4.05 life-years). Sensitivity analyses confirmed the robustness of our results except for a price reduction of 70% for AA or enzalutamide.ConclusionOur approach is innovative to the extent that our analysis considers various potential strategies for metastatic prostate cancer (mPC). Our economic evaluation suggests that a price reduction of AA or enzalutamide impacts on the results. This approach must continue, including new drugs for patients with mPC.     

Evaluation of antimicrobial treatments in children with acute otitis media in Spain: a pharmacokinetic-pharmacodynamic (PK/PD) approach

Pharmacokinetic/pharmacodynamic (PK/PD) principles are priceless tools for evaluating the effectiveness of different antimicrobial treatments for different infections. However, very few studies deal with pediatric dosages and take into account the unbound drug serum levels. Our study is focused on the most frequent antibiotic dosing schedules used in Spain for the treatment of acute otitis media (AOM) in children, where high rates of penicillin and macrolide resistance exist among pneumococcal isolates. Pharmacokinetic parameters of antibiotics in children where obtained from the literature. The minimum inhibitory concentrations (MIC90) of antibiotics for pediatric strains of Streptococcus pneumoniae and Haemophilus influenzae were obtained from the SAUCE 2 project. Only ceftriaxone (50 mg/kg single intramuscular dose) and high doses of co-amoxiclav (27-33 mg/kg q8h) provided adequate efficacy indexes (tss(%)>MIC) for both S. pneumoniae and H. influenzae in AOM in children. These results are consistent with MEF (medium ear fluid) levels obtained from the literature. Our results confirm the utility of serum unbound levels to predict efficacy of antibiotics in children with AOM.     

Economic evaluation of flap fixation techniques after mastectomy: Results of a double-blind randomized controlled trial (SAM-trial)

BackgroundAn economic evaluation was performed alongside an RCT investigating flap fixation in reducing seroma formation after mastectomy. The evaluation focused on the first year following mastectomy and assessed cost-effectiveness from a health care and societal perspective.MethodsThe economic evaluation was conducted between 2014 and 2018 in four Dutch breast clinics. Patients with an indication for mastectomy or modified radical mastectomy were randomly assigned to: conventional closure (CON), flap fixation with sutures (FFS) or flap fixation with tissue glue (FFG). Health care costs, patient and family costs and costs due to productivity losses were assessed. Outcomes were expressed in incremental cost-effectiveness ratios (ICERs): the incremental cost per quality-adjusted life year (QALY). Bootstrapping techniques, sensitivity and secondary analyses were employed to address uncertainty.ResultsThe FFS-group yielded most QALYs (0.810; 95%-CI 0.755–0.856), but also incurred the highest mean costs at twelve months (€10.416; 95%-CI 8.231–12.930). CON was the next best alternative with 0.794 QALYs (95%-CI 0.733–0.841) and mean annual costs of €10.051 (95%-CI 8.255–12.044). FFG incurred fewer QALYs and higher costs, when compared to the CON group. The ICER of FFS compared to CON was €22.813/QALY. Applying a willingness to pay threshold in the Netherlands of €20.000/QALY, the probability that FFS was cost-effective was 42%, compared to 37% and 21% for CON and FFG, respectively.ConclusionThe cost-effectiveness of FFS following mastectomy, versus CON and FFG, is uncertain from a societal perspective. Yet, from a health care and hospital perspective FFS is likely to be the most cost-effective intervention.     

Costs and effectiveness of staging and treatment options in early-stage Hodgkin's disease.

PURPOSE: Using a cost-effectiveness analysis, to weigh the costs and benefits of the different staging and treatment options in early-stage Hodgkin's disease. METHODS: We constructed a decision-analytic model for a hypothetical cohort of 25-year-old patients with early-stage Hodgkin's disease. Markov models were used to simulate the lifetime costs and prognosis of each staging and treatment strategy. Baseline probabilities and cost estimates were derived from published studies and bills of relevant patient cohorts. RESULTS: Among the six management strategies considered, the incremental cost-effectiveness ratio of laparotomy and tailored treatment compared with mantle and para-aortic-splenic radiation therapy in all clinical stage I-II patients was $24,100/quality-adjusted life year, while that of the strategy of combined modality therapy in all clinical stage I-II patients compared with laparotomy was $61,700/quality-adjusted life year. All the remaining strategies were dominated by one of these three strategies. Sensitivity analysis showed that the cost-effectiveness ratios were driven predominantly by the effectiveness rather than the cost of each strategy. In particular, the analysis was heavily influenced by the utility of the post-laparotomy health state. CONCLUSIONS: In considering the various alternative management strategies in early-stage Hodgkin's disease, even very small gains in effectiveness were enough to justify the additional costs of more expensive treatment options.     

The cost effectiveness of bevacizumab when added to capecitabine,with or without mitomycin-C,in first line treatment of metastatic colorectal cancer: Results from the Australasian phase III MAX study

BackgroundBased on the clinical data, bevacizumab has been approved in Australia and globally for the treatment of advanced colorectal cancer. However, limited evidence exists for its cost-effectiveness. The purpose of this study was to evaluate the cost effectiveness of adding bevacizumab to capecitabine monotherapy in patients with metastatic colorectal cancer, using data from the prospective economic evaluation conducted alongside the MAX trial.MethodsIndividual patient level data on resource use and progression free survival were prospectively collected in the phase III MAX trial. Resource use data were collected for the period between randomisation and disease progression, and unit costs were assigned from the perspective of the Australian health care funder. Effectiveness was measured in quality adjusted progression free survival years, with utility scores obtained from both the community valued EQ-5D questionnaire and the patient valued UBQ-C questionnaire. Progression free survival was used as a secondary effectiveness measure.ResultsThe addition of bevacizumab to capecitabine monotherapy cost approximately $192,156 (95% confidence interval [CI], $135,619 to $326,894) per quality adjusted progression free survival year gained when using publicly listed pharmaceutical prices and utility values from the EQ-5D questionnaire. This decreased to $149,455 (95% CI, $100,356 to $245,910) when values from the UBQ-C questionnaire were applied. The incremental cost per progression free survival year was $145,059 (95% CI, $106,703 to $233,225).ConclusionsBevacizumab was not found to be cost effective at its listed price, based on results from the MAX trial.     

An economic analysis of the INTEREST trial,a randomized trial of docetaxel versus gefitinib as second-/third-line therapy in advanced non-small-cell lung cancer

BackgroundThe INTEREST (IRESSA NSCLC Trial Evaluating Response and Survival against Taxotere) trial compared gefitinib with docetaxel (Taxotere) in pretreated advanced non-small-cell lung cancer (NSCLC). Noninferiority for overall survival was concluded. Gefitinib had a better toxicity profile and greater improvements in quality of life (QoL). We undertook a cost-consequence analysis to estimate the direct medical costs of gefitinib compared with docetaxel.Patients and methodsSummary data from INTEREST were used to derive resource utilization and direct costs from treatment start until drug discontinuation. Costs for treatment, adverse events, outpatient visits and investigations were calculated. Mean total cost-per-patient-per-arm was determined, and incremental cost was calculated. Utility values were generated from Functional Assessment of Cancer Therapy - Lung scores and compared between arms.ResultsIncremental mean overall cost per patient for gefitinib over docetaxel was CAD$5161. Drug was the major contributor to overall cost in both arms. Longer mean duration of gefitinib therapy (134 versus 91 days) contributed to the incremental cost difference. The cost per 21-day cycle was similar in both arms ($1963 docetaxel, $2095 gefitinib).ConclusionThe modest increase in cost associated with gefitinib supports its use as an alternative to docetaxel as second-line treatment of advanced NSCLC, particularly given the improvements in QoL, patient preference for oral therapy and better toxicity profile with gefitinib.     

Pharmacological aspects of the antibiotics used for urological diagnostic procedures

Abstract

Surgical antimicrobial prophylaxis is the use of an antibiotic before, during, or shortly after a urological procedure to prevent postoperative infections such as urinary tract or wound infection. The optimal antimicrobial drug must be microbiologically active against the most frequent potential pathogens and have good pharmacological properties.

Correct timing of antimicrobial prophylaxis is the first critical issue in determining treatment efficacy. The antibiotic must be administered before the start of the surgical procedure in order to ensure a high tissue level at the time of microbial contamination. If using an oral antibiotic, this must be administered 1–3 hours before the operation and a parenteral antibiotic should be administered at the induction of anaesthesia.

The antibiotics potentially useful for antimicrobial prophylaxis are the beta-lactams, cotrimoxazole, fluoroquinolones, and fosfomycin trometamol. The criteria for choosing the optimal antibiotic include an appropriate antimicrobial spectrum, favourable pharmacokinetic parameters (especially good tissue penetration), and elevated safety or tolerability. The use of cotrimoxazole must be restricted due to increasing chemoresistance. Unfortunately fluoroquinolone-based regimens, once the mainstay of prophylaxis guidelines, are increasingly ineffective due to a constant increase in multidrug-resistant (MDR) Gram-negative bacteria. The same concerns apply with regard to the second and third generation cephalosporins that have problems of resistance and, if administered orally, do not sufficiently penetrate prostatic tissue. An appropriate beta-lactam could be an aminopenicillin combined with a beta-lactamase inhibitor.

Fosfomycin trometamol can also be a good potential choice due to its elevated activity against MDR Gram-negative bacteria and its favourable pharmacokinetic parameters, including an elevated penetration into prostatic tissue.