Abstract
Background: Recurrent urinary tract infections are of importance for public health as most clinicians are faced with repeated and long-term administration of broad-spectrum antimicrobial agents leading to an increased risk of resistant bacteria. One encouraging treatment approach may be individualized homeopathy. Case Reports: Here, four female cases with recurrent urinary tract infections are reported. They were treated successfully with the homeopathic strategy after several conventional approaches revealed no improvement. The follow-up period was a minimum of 3 years and the frequency of episodes with urinary tract infection as well as of antibiotic treatment was documented. Additionally, the patients were asked to assess the treatment outcome retrospectively in a validated questionnaire. Results: The treatment resulted in a reduction of urinary tract infections and the need for antibiotics from monthly to less than 3 times a year. Three of the four women had no cystitis and related intake of antibiotics for more than 1.5 years. A relapse of symptoms could be treated efficiently with a repetition of the homeopathic remedy. All subjective outcome assessments resulted positive. Conclusion: This case series suggests a possible benefit of individualized homeopathic treatment for female patients with recurrent urinary tract infections. Larger observational studies and controlled investigations are warranted.
Zusammenfassung
Hintergrund: Rezidivierende Harnwegsinfektionen (RUTI) haben große Bedeutung für das öffentliche Gesundheitswesen, da die meisten Kliniker therapeutisch auf wiederholte und langzeitige Verabreichung von Breitbandantibiotika zurückgreifen, was wiederum zu einem erhöhten Risiko für resistente Bakterienstämme führt. Individualisierte Homöopathie (iHOM) könnte eine Behandlungsalternative sein. Kasuistiken: Zwischen Ende 2013 und August 2015 wurden vier Frauen mit RUTI in einer Universitätsambulanz mit iHOM behandelt, nachdem mehrere konventionelle Ansätze ihre Situation nicht verbessern konnten. Alle Patientinnen wurden mindestens drei Jahre lang beobachtet und die Häufigkeit von Harnwegsinfekten (UTIs) sowie von Antibiotika-Behandlungen (AB) dokumentiert. Zusätzlich wurden die Patienten gebeten, das Behandlungsergebnis in einem validierten Fragebogen nachträglich zu bewerten. Ergebnisse: Die Häufigkeit von UTIs und der Bedarf an AB wurden von monatlich auf mindestens weniger als 3-mal pro Jahr reduziert. Drei der vier Frauen hatten länger als 1,5 Jahre keine Blasenentzündung oder antibiotische Therapie. Ein Rückfall der Symptome konnte jeweils mit einer Wiederholung des homöopathischen Mittels effizient behandelt werden. Alle subjektiven Ergebnisbeurteilungen fielen positiv aus. Schlussfolgerung: Diese Fallserie legt einen möglichen Nutzen von iHOM für Patienten mit RUTI nahe. Der therapeutische Ansatz sollte in größeren, kontrollierten Studien erforscht werden.
SchlüsselwörterRezidivierende Harnwegsinfektionen, Bewusstsein für antimikrobielle Substanzen, Ergänzende und alternative Medizin, Individualisierte Homöopathie
Introduction
Urinary tract infections (UTI) [1] are experienced by many women: up to 40% get at least one UTI with consecutive antibiotic (AB) treatment during their lifetime [2, 3]. Approximately 12% suffer from recurrent urinary tract infections (RUTI), defined as more than two episodes within 6 months or three or more episodes within 12 months [4]. Practitioners are faced with frequent and/or prolonged administration of broad-spectrum antimicrobial agents. This leads to the growth of drug-resistant bacteria and to the destruction of the commensal intestinal and vaginal flora [5] and might lead to persistent infections and/or damage of the urinary tract [6]. Therefore, and in view of the increasingly virulent bacterial strains, a new strategy other than administration of antimicrobial prophylaxis against RUTIs in women should be developed. Different unproven therapies have gained attention and are currently being evaluated [7].
It is claimed that the resistance to recurrent infections can be increased with individualized homeopathic therapy (iHOM) [8] and iHOM has proven clinical effectiveness in treating recurrent upper respiratory tract infections [9, 10]. In this respect, it seems reasonable to test, whether this accounts as well for RUTIs. In order to provide a base for further evaluation of this hypothesis, a case series of four women treated with iHOM for RUTI is presented in this article. The treatment approach, evolution of the cases, as well as possible conclusions are discussed.
Material and Methods
The data derives from the Institute of Complementary and Integrative Medicine, IKIM, at the University of Bern, Switzerland. In the setting of an outpatient clinic for patients with chronic health problems four women with RUTI, who consulted IKIM between November 2013 and August 2015, were treated with iHOM and their cases analyzed retrospectively. Three of them were transferred from the University Women’s Hospital, Bern (WHB), and one presented herself after recommendation of a friend. The women had RUTI for more than 10 years and more than 10 courses of AB drugs during the past 12 months, each. The four patients had been diagnosed with RUTI prior to the reference to IKIM using a thorough history, urine cultures, as well as abdominal and vaginal examination. Urine cultures mostly showed growths of pan-sensitive Escherichia coli. All patients had been treated unsuccessfully with several conventional approaches and needed a course of AB at least every 2 months at the time of presentation.
During the first visit at the outpatient clinic at IKIM, the patients underwent a case-taking with the features of iHOM and received a prescription according to the principles of this method following the “Law of Similars”: they received a single homeopathic remedy, which was selected after a process of matching the totality of the patients’ present symptoms with those described in the homeopathic medicines’ textbook “Materia Medica” for the specific remedy [11]. Totality in this respect means that the concomitant diseases, feelings, and psychological features may also be taken into account for the prescription [9]. The remedies were obtained from two pharmacies, either Spagyros® [12] or Schmidt-Nagel® [13], approved by the Swiss Agency for Therapeutic Products (Swissmedic), and were prepared following the instruction of the European Pharmacopoeia [14], Monograph 1038 [13] and 2045 [12], and the German Homeopathic Pharmacopoeia [15]. During this preparation, remedies are highly diluted and succussed, resulting in so-called homeopathic “potencies.” The doctor at IKIM [16], who treated the women [16], is trained in general medicine and holds a diploma for iHOM. She chose the remedies for the patients using the practitioner edition of CompleteDynamics repertory [17]. “C-potencies,” in which the original substance is diluted 1:100, followed by 10 succussions and “Q-potencies,” in which the original substance is diluted 1:50,000, followed by 2–10 succussions were prescribed for the cases presented here. In case of infection, commonly the dosage of C-potencies was a single sublingual dose of 5 Globules, followed by 1× 5 Globules dissolved in 500 mL tap water. Patients were told to shake the dilution before every use. Frequency of follow-up visits and changes of the treatment were flexible, total observation time was from first consultation (November 2013 – August 2015) until August 2018. Reporting was orientated following the HOM-CASE guidelines [18] and the modified Naranjo criteria were assessed independently by all authors post hoc. Approval from the local ethical committee was obtained and written informed consent was obtained by all patients.
Frequency of UTI episodes as well as frequency of AB were documented by the doctor in the patient’s files. Additionally, patients were asked to assess the treatment outcome retrospectively in a validated questionnaire on Outcome Related to Impact on Daily Living (ORIDL) [19]. The English assessment form was translated by the treating doctor for the patients’ convenience.
Cases
Case 1
This 44-year-old patient was referred from WHB. On the first consultation in March 2014, she reported suffering from RUTI for 10 years, but for 1 year, she had rarely had symptom-free days. She complained of constant dysuria with flare-ups of severe pain. On monthly intervals, she took AB, which reduced the pain but did not bring full relief. Previous treatment approaches (Table 1) had been without effect. Evident symptoms of the homeopathic case-taking were shooting pain from the urethra upwards and a constant feeling of sickness. “I feel rotten inside,” she said. The homeopathic evaluation (online supplement 1; for all online suppl. material, see www.karger.com/doi/10.1159/000504317) in this case pointed to the remedy Lac-caninum (Lac-c), which she received [12].
Evolution. After 1 month, she reported no dysuria anymore. The pain had slowly decreased after intake of the remedy and she had no more outburst of pain or cystitis. The feeling of sickness was initially better, but reoccurred and she had the feeling of standing next to herself as if she were two persons. As this last symptom is described in the homeopathic textbooks for Lac-c, it was considered as a reaction to the remedy (known as “proving-symptom” in homeopathic teachings as described below). For her relief, she was prescribed Lac-c Q5 [12], 3 drops in 100 mL tap water daily for 1 month. Four months later, she told in the follow-up that she had no UTI or discomfort and felt healthier overall. However, subsequently, on return from holidays, she had cystitis, which she treated with AB (Fosfomycin), after which she felt sick again. Thus, she received Lac-c C1000 [12] in the same dosage as the C200 5 months before. With this treatment, the main symptoms (pain and sick feeling) disappeared for 4 months. In December 2014, she reported another confirmed UTI treated with AB and she received another dose of Lac-c C1000 [12]. Thereafter, she reported no more cystitis for the rest of the observation time in August 2018. At this point, she was asked to assess the homeopathic treatment. She writes that she sometimes has a slight irritation of the bladder but no UTI. Her rating of the treatment effect for RUTI was +4 (cured/back to normal) on the 8-point scale for the main symptom and the general well-being (Table 2).
Case 2
This postmenopausal lady with 53 years of age was also referred from the WHB. In April 2014, she reported problems with RUTI since her first pregnancy over 20 years back. Over the last 3 years, she needed to take AB every month. Two months ago, she stopped AB for acute episodes of UTI and said that ever since, she has daily dys- and pollakisuria. She already tried AB prophylaxis and Uro-Vaxom® (lyophilisated Escherichia coli bacteria), but no supplementary vitamin C, because the dysuria gets worse and she gets dyspepsia when she takes sour food or drinks supplements. The extended case-taking revealed that she felt exhausted and intoxicated and the dysuria was worse from physical exertion. Further, she had left-sided numbness of the right arm, sometimes right-sided facial pain, and wandering joint pains, respectively. These symptoms had not been examined by a doctor so far and she said that she only goes to doctors if she really needs it. She was prescribed Berberis C200 [12], according to the laws of similar (online supplement 1). Additionally, she received D-mannose, 2× 1 teaspoon daily.
Evolution. Initially, there was no reaction to the homeopathic remedy, consequently the potency was raised to Berberis C1000 [13]. But this did not bring any improvement either. D-mannose caused severe meteorism and she stopped it after a month. Three months after the first consultation, the remedy was changed to Pulsatilla (Puls) C200 [12] (online supplement 1). After the intake, she had an aggravation of dysuria, which lasted for 3 days, followed by self-reported symptom relief and improvement of general well-being of 70% each. The amelioration lasted for a month, after which she had cystitis confirmed by urine examination. She took non-steroidal anti-inflammatory drugs and the potency of Puls was raised to C1000 [13]. Another short aggravation of symptoms was followed by an improvement. By the end of the fifth month of treatment, 30% of the complaints were remaining. The potency was then changed to Q3 [12], 3 drops in 100 mL tap water, to be taken daily. After another month of treatment, all UTI symptoms had disappeared and the medication was discontinued (September 2014). During the treatment, no effect on the joint and facial pains and numbness was reached, but the patient reported these symptoms to be less prominent and that she feels generally better.
The patient contacted IKIM again because she had a relapse of symptoms after more than 3 years (March 2018). She had already taken Puls C1000 [13] without effect. As the homeopathic evaluation still pointed to Puls as the matching remedy, the latter was given in a higher potency (C10000) [13]. As 3 years before, she reported a short aggravation for 2 days, followed by a relief of symptoms and no further UTI for the remaining 5 months of observation time. This woman reported major improvement of the main complaint and slight improvement of the general well-being (Table 2). She has not needed any more courses of AB since she started iHOM treatment in April 2014.
Case 3
The patient was referred from WHB in November 2013. She was 30 years old and suffered from recurrent cystitis and constant vulvar burning for 18 years. For 15 years, she needed AB every 2 to 4 weeks. Other treatment attempts had been fruitless (Table 1). In the homeopathic case-taking, she also reported several fears: of robbery, of darkness, of accidents. She repeatedly had dreams in which her family died and when waking up, she noticed dried-up tears on her face. Otherwise, she was healthy but had severe dysmenorrhea and prolonged menses. All symptoms were better from local warm applications. She was prescribed Causticum (Caust) C200 [12] (online supplement 1).
Evolution. One month later, there was nearly no vulvar burning noted. Once, she had accentuated dysuria; for this, she used dissolved globules as she had been instructed. This relieved the acute symptoms. For the residual vulvar burning and persistent fears, she was prescribed Caust Q3 [12], 3 drops in 100 mL tap water, to be taken daily, followed 1 month later by Caust Q5 in the same dosage. In the follow-up visit 6 months later, she reported no further UTI and only slight dysuria in the morning. She rated the symptoms of the urinary tract as 90% improved, the vulvar burning was 50% better, and the fears were 20% less. The dysmenorrhea was unchanged. Therefore, she received the potency Caust C1000 [12], 5 globules once and Q7 drops [12] on demand in case of anxiety. After another 2 months, she reported further improvement of the vulvar burning (up to 70% in total) and the phobias (30–40%), but no further change concerning the pains during menses. She was told to take Caust C1000, daily 3 drops of a liquid dilution of water and ethanol and shake the dilution before every use. This was not possible, because the patient did not manage to produce such a dilution. On the other hand, she reported at her last visit in Mai 2015 that she stopped genital washing with a gel and only uses water. Since then, the vulvar burning had gone completely. Although the dysmenorrhea persisted further, she stated also that she is happy with what had been attained: rarely cystitis, no more burning, and more confidence in life. Her ratings in the questionnaire [19] were major improvement of the main complaint and slight improvement, affecting daily living for the general well-being (Table 2).
Case 4
In the beginning of August 2015, this 79-year-old woman presented at IKIM with RUTI after recommendation by one of the other patients. She stated that she needed to take AB every 2 months for 2 years and every time she needs to do so, she feels unwell for a month. She started having UTI after she had hysterectomy 6 years prior. Since then, she has had a relapse whenever she is not careful enough not to get cold, but also without apparent reason. If she gets cystitis, she feels a constant pain in the bladder, the urine is sometimes bloody, and she becomes moody. When asked about her general symptoms and character, she described herself as fastidious and sometimes irritable. She fears to lose her husband. Her ailments suited symptoms described for Arsenicum album (Ars-a), which was prescribed [12] (online supplement 1).
Evolution. One day before she started the treatment, she had cystitis confirmed by urine examination and she took AB and Ars-a C200 together. Within a few hours, the symptoms disappeared, which was much quicker than the patient knew from treatments with AB. Two weeks later and again after 3 weeks, she had another UTI, which both resolved within a day with Ars-a C200 only. After another 6 weeks, symptoms of cystitis developed again, but this time Ars-a C200 did not help. Thus, she was told to take Ars-a C1000 [12], after which she had more intense symptoms for a day, followed by disappearance of symptoms and absence of UTI for 1.5 years. Within the first 2 months of treatment, she experienced some improvement of her mood. She said that she felt afflicted by the frequent UTI and that was why she feels better now.
She was seen at IKIM in April 2018 after a partial colectomy for chronic diverticulosis with a wound infection and cardiac rehabilitation and reported that since January 2018, she had another 4 UTI with increasing frequency. She did not know which homeopathic remedies she should take, but now, she wanted to try again with homeopathy. Initially, she was given sublingual single doses of Ars-a C200 and C1000 [12] again but still had 2 more UTI until June 2018. For the treatment of the second of these UTI, the remedy was changed to Staphysagria C200 [13] (online supplement 1). This remedy rapidly led to improvement of the acute symptoms. Since then, she had had no more cystitis. This patient assessed the treatment effect as slightly improved without any change regarding the general well-being in April 2018.
Results
Patient characteristics are summarized in Table 1. The four patients presented with a history of RUTI lasting an average of 13.5 years (range 6–20). All reported increasing frequency of UTI episodes, occurring at least monthly over the preceding 10 months. All women had tried several other forms of therapies, including weekly intake of AB as prophylaxis and oral administration of immune-active Escherichia coli fractions (Uro-Vaxom®) and D-mannose, a monosaccharide which may reduce bacterial load intravesically and in the urinary tract [20]. They claimed side effects from the frequent intake of antibiotics and presented themselves in search of an alternative.
In summary, all patients treated using iHOM reported fewer UTI episodes and courses of AB, without any persistent, severe, or unpleasant side effects from iHOM. The subjective outcome assessments (ORIDL) are summarized in Table 2. The additional modified Naranjo assessment as part of the HOM-CASE guidelines revealed 8 to 10 points (range 0–13 points) for each patient (online supplement 2).
Discussion
Treatment options for RUTIs are limited and not always successful [3]. Reasons for treatment failure and reoccurrence, respectively, are multifactorial [5, 6]. They might also be related to lifestyle factors [3]. Within this case series, patients with a long history of RUTI had frustrating attempts of several treatment options including complementary treatments, such as immune-prophylaxis and herbal therapy. Our approach of iHOM resulted in a positive outcome, both objectively (by reducing the frequency of UTI and the amount of AB courses) and subjectively (ORIDL assessments). In detail, all women had received AB once a month for more than 1 year at the time of first consultation. Three of the four patients had no cystitis for 18, 24, and 36 months, respectively, after treatment with 3 or 4 doses of individually prescribed homeopathic remedies in high potencies. The fourth patient experienced disappearance of permanent dysuria and reduction of frequency of UTI from once every 2 weeks to 2–3 times per year.
Regarding safety, no adverse effects occurred; however, we observed two harmless undesirable effects of the prescribed remedy, as classified by Stub et al. [21]. In the first case, the patient reported a new symptom after the intake of the remedy Lac-c C200 (feeling of standing next to her). This symptom is described in the homeopathic text book (Materia Medica) for Lac-c. The text book contains the symptoms which were exhibited by healthy persons after the intake of a specific remedy in homeopathic pathogenetic trials [22, 23]. These symptoms can also occur during a homeopathic treatment and are then classified as proving symptoms. They usually subside over time. In the second case, temporary worsening of the symptoms to be treated corresponds to a homeopathic aggravation, which manifest in some patients after administration of the individually correct remedy. Normally, this aggravation is of short duration and followed by a general improvement. In a meta-analysis of randomized controlled studies, it was found that 68% of reported adverse effects and 98% of homeopathic aggravations were classified as grade I according to the common terminology criteria for adverse effects (CTCAE) [24, 25].
The independently rated modified Naranjo assessment resulted in scores between 8 and 10 out of 13 points for each patient (online supplement 2). Unfortunately, no guidance on how to interpret this data from this assessment exist so far. In these four cases, the authors were not sure if the reported frequency of UTI and courses of antibiotics constitutes an objective outcome. If the endpoint was not considered as objective, the score would still show a 50% probability of the effect being related to homeopathic treatment. Taken together, the self-reported reduction of courses of AB intake was judged as fairly reliable by the authors.
In addition to this case series, there is another pilot study reporting positive results of iHOM for RUTI in patients with neurogenic lower urinary tract dysfunction due to spinal cord injury [26]. In this controlled clinical observation, iHOM is compared not only to conventional standard therapy but also to various other treatment options.
The data of observations reported here should be handled with caution as they are derived from only four cases, and various factors, including spontaneous remission and unreported co-interventions, could have contributed to the positive effects. Therefore, the findings are likely to be confounded by unidentified factors and no generalizable conclusions can be drawn. Nonetheless, iHOM appears to be a promising treatment option for RUTI, where results are often disappointing [3‒5]. Additionally, iHOM seemed also effective in the handling of acute episodes of UTI in cases 3 and 4.
Against the background of increasing problems with antimicrobial resistance, iHOM should be evaluated further in controlled clinical trials and studies with mixed-method approaches as a new approach for treatment of RUTI and acute uncomplicated UTI.
Conclusion
In this case series, iHOM resulted in a reduction of frequency of UTI and use of AB, respectively. The results do not exclude a recovery due to other factors or regression to the mean. Still, the evolution of the disease in analyzed patients suggest that iHOM might be a reasonable approach for the treatment of RUTI. It should be further investigated with prospective open-label and controlled studies.
Acknowledgments
To the patients, their family doctors, and the referring doctors from the University Women’s Hospital, Bern.
Statement of Ethics
Jurisdiction of the Ethics Committee of the Canton Bern was obtained with the Project ID 2017-01515 after the agreement of the patient that the coded case data will be summarized and evaluated. Informed consent for publication was given by the patients. The signed documents are confidential.
Disclosure Statement
The authors are homeopathic doctors and have no financial interests to declare.
Availability of Data and Materials
Data of this report is confidential. Anonymized material can be obtained from the author.
Funding Sources
No funding was obtained for this case report and the preparation of the manuscript.
Author Contributions
Dr. med. K. Gaertner is responsible for data documentation and the preparation of the manuscript. Dr. med. M. Frei-Erb supervised the first author, and Dr. med. K. von Ammon proofread and commented the manuscript.