Are Ureaplasma and Mycoplasma responsible for Bladder Pain Syndrome and other urogynecological diseases such as overactive bladder or Urethral Syndrome?

We have read an article titled “A Systematic Review of Mycoplasma and Ureaplasma in Urogynaecology” written by doctors Nina Combaz-Söhnchen and Annette Kuhn from the Maternal and Child Hospital of Bern, Switzerland and published in the magazine of Obstetrics and Gynecology “Geburtshilfe und Frauenheilkunde” in 2017, Switzerland.

Mycoplasmas

The Mycoplasmataceae (family that includes all the species belonging to the genera Mycoplasma and Ureaplasma) belong to the class of Mollicutes and are commonly called “mycoplasmas”.

These bacteria are very different from common uropathogenic germs (morphology and way of life point of view). In fact they are:

– much smaller

– with extremely small genome

– devoid of cell membrane

– without pilis

– with a limited capacity for biosynthesis (for example, metabolism, reproduction, etc.)

– with significant sensitivity to environmental factors

– resistant to antibiotics

Therefore, these microorganisms have high requirements in terms of living conditions.

For this reason, Mycoplasmas colonize humans as parasites do intracellularly and extracellularly since they need to find an organism that hosts them to survive.

Pathogenicity of Mycoplasmas

Among the 200 Mycoplasma species that attack the human body, only 6 appear to be pathogenic in immunocompetent humans: Mycoplasma pneumoniae, Mycoplasma hominis, Mycoplasma genitalium, Micoplasma fermentans, Ureaplasma parvum and Ureaplasma urealyticum.

However, it should be noted that 3 species of Mycoplasmas are significantly present in the genital tract (Mycoplasma hominis, Mycoplasma genitalium and Ureaplasma urealyticum) where they can be present as commensal agents of Doderlein flora or also potentially pathogenic (opportunistic in case of dysbiosis, for example). Research indicates that the number of sexual partners in the months prior to testing has an impact on the prevalence of bacterial colonization in the urogenital tract by these strains.

Mycoplasmas can cause many “discomforts”, especially genital ones which are often chronic and mainly affect men.

Due to the anatomical proximity of the female urethra and the vagina, it can be assumed that vaginal bacterial colonization could also reach the urinary tract. There is already a lot of information on sexually transmitted diseases (STDs), therefore on genital pathologies associated with Mycoplasmas.

Still, the influence and pathogenic potential of Mycoplasmas in the context of urinary tract infections and other urological disorders, such as overactive bladder and Bladder Pain Syndrome/Interstitial Cystitis, are still unclear.

However, its presence has been identified in particular in cases of urethritis, cystitis and infections of the upper urinary tract (kidneys, ureters). Its role in overactive bladder situations and Bladder Pain Syndrome/Interstitial Cystitis continues to be debated.

Mycoplasma hominis and Ureaplasma urealyticum have also been shown to be equally responsible for pyelonephritis (a complication of lower, even asymptomatic, urinary tract infection).

Can Mycoplasma cause overactive bladder (OAB) or Bladder Pain Syndrome/Interstitial Cystitis (SVD/IC)?

Many recent studies have found a high prevalence of the presence of certain Ureaplasma and Mycoplasma species in the urine of women with overactive bladder or BPS/IC. The authors also demonstrated that symptoms improve in patients with BPS/IC after targeted antibiotic therapy.

Mycoplasmas: when to look for them?

The authors emphasize in this work that in case of:

– existence of “unexplained” chronic urinary disorders and/or persistent symptoms similar to those of a lower urinary tract infection or pyelonephritis and/or chronic urethral symptoms

– presence of standard negative or polymicrobial urine cultures on a recurring basis

– lack of response to the usual antibiotics

a Mycoplasma search would be necessary before performing expensive and/or invasive diagnostic procedures (such as cystoscopy, MRI, urodynamic evaluation, etc.).

What are the best methods to detect Mycoplasma?

Most uropathogenic microorganisms can be detected in standard culture tests (ECBU), while Mycoplasma species must be specifically analyzed by specific tests. They can also be found in both asymptomatic and symptomatic patients.

Due to its (intracellular) contamination patterns, the number of bacteria in the urine is not necessarily related to the amount of bacteria actually present in the bladder wall. In fact, a significant number of these intracellular organisms can be found in the bladder wall in the absence of bacteriuria. That is why the test of choice for detection of Mycoplasmas is urethral sampling.

Mycoplasma genitalium is not detected with a standard culture due to extremely slow growth. The real-time polymerase chain reaction (PCR = “polymerase chain reaction”) is the diagnostic method used because it is the fastest method to obtain a reliable result.

In contrast, Ureaplasma urealyticum and Mycoplasma hominis can be identified by culture or PCR.

In case of a positive result, the most difficult decision is in the hands of the doctor who must interpret the result (also taking into account the symptoms) to conclude if the identified bacteria is pathogenic or not and, therefore, to implement the treatment according to the antibiogram.

Treatment of Mycoplasmas and Ureaplasmas

The study cited above specifies several aspects related to treatment:

– antibiotics to choose, dosage and dosage

– such therapy should only start when the test results (in particular the antibiogram) are available to prevent and avoid antibiotic resistance

– the treatment should also be extended to the partner

– the use of condoms is essential until the problem is completely resolved

Conclusions of the study

The study authors conclude that, given the current situation (2018), Mycoplasmas should be specifically searched with a urethral sample and then a PCR analysis in patients with recurrent infections or when standard microbiological cultures are negative.

In women with symptoms, treatment should always be agreed according to the result of the antibiogram since the intracellular nature of Mycoplasmas renders the conventional antibiotic ineffective. It can be assumed that in women prone to chronic cystitis or suffering from apparently urogenital bacterial symptoms, these difficult-to-reveal pathogens often play an underestimated role.

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