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FIRST INDIVIDUALISED BACTERIOPHAGE INTRAVENOUS TREATMENT OF A PATIENT IN THE CZECH REPUBLIC

European Statement

Production and Compounding

Author(s)

Michal Kočí, Kateřina Grygarová

Why was it done?

Individualised bacteriophage therapy has not previously been used in the Czech Republic. A polymorbid patient was treated for over two years for recurrent spondylodiscitis caused by methicillin-resistant Staphylococcus aureus (MRSA). Despite various antibiotic regimens, the infection could not be controlled, leading to repeated hospitalisations. Based on international experience, the medical-head of the infectious diseases department asked the hospital pharmacy to procure a bacteriophage medicine active against the patient\’s specific pathogen.

What was done?

The objective was to analyse the legislative pathway and subsequently secure approval for, prepare, and administer individualised phage therapy as a salvage treatment for a patient with a chronic, antibiotic-resistant infection.

How was it done?

In collaboration with the infectious disease clinic and a domestic phage manufacturer, the optimal regulatory route was identified and an approval for using the active pharmaceutical ingredient containing bacteriophage for final drug preparation was requested from the Ministry of Health and the State Institute for Drug Control. The hospital pharmacy coordinated the entire submission process, overcoming regulatory and production challenges. Following approval, the pharmacy secured the delivery and developed a new Standard Operating Procedure (SOP) for the aseptic preparation of the phage lysate for intravenous administration.

What has been achieved?

After successfully obtaining all approvals, the pharmacy prepared and dispensed 35 intravenous infusions. Following the therapy, the patient has remained symptom-free for nine months and significant clinical improvement was observed. The infection is currently considered effectively treated, and no further infection-related hospitalisations have been necessary. This outcome demonstrates the successful implementation of a complex therapeutic strategy, from regulatory navigation to clinical application.

What next?

This pioneering initiative demonstrates that individualised bacteriophage therapy might be, in some cases, a feasible and safe option for patients with untreatable, multi-resistant infections. It highlights the crucial role of the hospital pharmacist in this process. Significantly, this first-in-country application sparked a nationwide expert debate and directly contributed to the establishment of a Ministry of Health working group on bacteriophages. This established pathway could be transferable to other Czech hospitals, and possibly even to other European countries.

Application of new indicators of antimicrobial agent use based on consumption in a tertiary hospital

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European Statement

Patient Safety and Quality Assurance

Author(s)

Saúl Herrera Carranza, Carlos Sanz Sánchez, Sira Sanz Márquez, José Francisco Valverde Cánovas, Leonor Moreno Núñez, Ana Vegas Serrano, Rafael Hervás Gómez, Oriol Martín Segarra, Juan Emilio Losa García, Montserrat Pérez Encinas

Why was it done?

Spanish Society of Hospital Pharmacy(SEFH) proposed 13 indicators(bibliography:Gutiérrez-Urbón JM, Gil-Navarro MV, Moreno-Ramos F, Núñez-Núñez M, Paño-Pardo JR, Periáñez-Párraga L. Indicators of the hospital use of antimicrobial agents based on consumption. Farm Hosp. 2019;43(3):94-100) which could help to improve the quality of antimicrobial use.
Indicators are related directly(dir): higher value-better practices; indirectly(ind):lower value-better practices; or heterogeneity: homogeneous percentages(%)-better practices.

What was done?

The creation of a tool for calculating new indicators of antimicrobial agents based on consumption using Defined Daily Dose per 100 hospital stays(DDD/100s).

How was it done?

We built an Excel tool to input required data in order to calculate the indicators with the formulas defined for their automated estimation:
-Overall antibacterial consumption(ind)
-Overall consumption of antifungals(ind)
-Consumption of carbapenemics(ind)
-Consumption of fluoroquinolones(ind)
-Ratio macrolides-p/fluoroquinolones-p(dir)
-Ratio metronidazole-p/piperacillin-tazobactam+carbapenemics(dir)
-Fosfomycin consumption(dir)
-Sequential therapy(dir)
-Ratio anti-SRSA/anti-MRSA agents(dir)
-Ratio amoxicillin/amoxicillin-clavulanic acid(dir)
-Ratio amoxicillin-clavulanic acid/piperacillin-tazobactam(dir)
-Diversification of anti-pseudomonas beta-lactam(heterogeneity): %anti-pseudomonal carbapenemics, %piperacillin-tazobactam and %anti-pseudomonal cephalosporins+aztreonam.
— Ratio fluconazole/equinocandins (dir)
DDD/100s for the years 2018-2022 were calculated in order to see the annual evolution. Required data: antibiotic (ATC Group: J01) and antifungal (ATC Group: J02) consumption by drug and route of administration (oral (o), parenteral (p) and others). Calculation of DDD/100s according to grammes consumed (obtained with Hospital Pharmacy software) and ATC/DDD-Index (World Health Organization). To visually analyse results, graphs were included.

What has been achieved?

We realised that our hospital improved by decreasing consumption of antibacterial, antifungal, carbapenemics and fluoroquinolones; and so, an early parenteral-oral switch.
However, the other ratio-based indicators are stable or worsening yearly: macrolides-p/fluoroquinolones-p, metronidazole-p/piperacillin-tazobactam+carbapenemics, fosfomycin consumption, anti-SRSA/anti-MRSA agents, amoxicillin/amoxicillin-clavulanic acid, amoxicillin-clavulanic acid/piperacillin-tazobactam, fluconazole/equinocandins and diversification of anti-pseudomonas beta-lactam.

What next?

These indicators provide possible improvement actions to enhance the use of antimicrobial agents. Consumption of fosfomycin or amoxicillin/amoxicillin-clavulanic acid ratio should be cautiously analysed due to outpatient (or in emergencies) management of uncomplicated infections. As improvement actions in our hospital, increase the use of metronidazole-p in anaerobic infections or cloxacillin and cefazolin de-escalation can be promoted as soon as sensitivity is confirmed by antibiogram-test. Diversify antibiotic pressure on pseudomonas, trying to reduce piperacillin-tazobactam by prescribing ceftazidime or cefepime, and reserving aztreonam for beta-lactams allergics. Similarly, decrease piperacillin-tazobactam use by prescribing amoxicillin-clavulanic acid if anti-pseudomonal coverage is not necessary.

Implementation of an Antibiotic Stewardship Program in Primary Care

European Statement

Clinical Pharmacy Services

Author(s)

CLARA NOTARIO DONGIL, ALEJANDRO MARCOS DE LA TORRE, MARÍA CARMEN CONDE GARCÍA, MARÍA MAR ALAÑÓN PARDO, BEATRIZ PROY VEGA, NATALIA ANDRÉS NAVARRO

Why was it done?

Most of the cultures performed in outpatients were not reviewed or were reviewed too late. An early detection for an adequate control of multidrug-resistant bacteria and the setting of a targeted antibiotic treatment, in case of being necessary, was the aim of this project. Hence basis for the implementation of an ASP is laid down, giving also advice to medical staff regarding appropriate antibiotic treatments.

What was done?

Multiresistant bacteria containment is a public health priority. Antibiotic Stewardship Programs (ASPs) can help to enhance patient outcomes by improving antibiotic prescribing. ASPs are common in hospitals, but are not usually available in primary care.

How was it done?

1- A circuit between microbiology laboratory staff, preventive medicine and pharmacy service was done. The first two collaborated by presenting data from lab results.
2- Cultures of multidrug-resistant species of outpatients were included. Results were interpreted by a hospital pharmacist on a daily basis.
3- A circuit of telephone calls between pharmacy and primary care was settled in order to communicate high epidemiological impact species detected. Pharmacist collaborates by giving advice regarding the right drug, right dose and right time, only when antibiotic treatment was necessary. Reports were registered on the medical history.
4- Variables collected in database were: age, sex, institutionalized, antibiotics received, kidney disease, culture type, specie.

What has been achieved?

During five months, 52 patients were included (52% male, 48% female). Mean age: 68 years. 11% institutionalized patients. 31% presented kidney disease.
Urine culture (58%),skin culture (13%), bronchial/sputum culture (12%), stool culture (12%), , and other cultures (5%) were analysed. Multidrug-resistant species (spp) were: Klebsiella spp (34%); Pseudomonas spp (8%); Mycobacterium spp (6%); other spp (52%).
17 pharmacist interventions were carried out, all of them related to appropriated treatment. 2 patients were hospitalized in order to receive parenteral antibiotic.

What next?

Optimizing antibiotics use is important to effectively treat infections. Identifying species that generate therapeutic difficulties is essential. Pharmacist advice could reduce treatment failures applying efforts to improve antibiotic use, being link of union between hospital and primary care. Other activities such as providing training to medical staff or spread results regarding to the use of antibiotics will be critical for ASP development.