Discussion of Creds activities and his four publications with the same title

In Credé's case there was an urgent medical need for an effective prophylaxis against gonorrheal ophthalmia neonatorum. Credé realized that vaginal douches were almost ineffective in preventing ophthalmia neonatorum, and that a strong antiseptic agent for prophylactic application at the ocular infection site - the newborn's eye - was needed. Potential irritative side effects had to be tolerable at this sensitive organ. Further, he recognized the threat of re-contamination of the eye by vaginal discharge especially in the first weeks after delivery so that strict hygienic requirements as well as teaching and education on this aspect became necessary and were introduced.

Credé reduced the concentration of the 2.5% silver nitrate solution (eye drops) that he used initially to 2.0% and immediately recognized that he was "on the safe side" with this regimen, reducing the incidence of ophthalmia neonatorum from approximately 10% to 0%. Adverse effects of chemical eye irritations were considered insignificant or even almost ignored most probably due to the high medical benefit obtained by this technique.

In contrast, Hecker's tests and results with 1% silver nitrate solution were not properly analyzed, although, to our knowledge today, a 1% solution of silver nitrate would also have been appropriate with comparable effectivity but less irritative adverse effects at the eye. Credé was convinced of the urgent need of enforcing such an eye prophylaxis as soon as possible and there was obviously no time left for him for a proper dose finding study, e.g., verifying or falsifying Hecker's observations.

Further, Credé solely acted as a clinician and did not join the scientific activities around the Micrococcus/Diplococcus and gonorrhea discussion, which were driven by Neisser and were highly contemporary, within just years 1879 (first paper of Neisser describing the Micrococcus microscopically [33]) to 1882 (Neisser's second, review publication on the Micrococcus with positive cultivation and inoculation results [34]). To the present author, it still remains an open historic miracle, as to why these two outstanding persons, Credé and Neisser, did not recognize each other appropriately. Credé could have obtained a lot of additional scientific merits by joining these discussions and activities, but despite this he strictly focused on the clinical aspects of prophylaxis of ophthalmia neonatorum, most probably to speed up and to enhance the pressure for an establishment of his prophylactic regimen as soon as possible. Crede, therefore, focused strictly on the obstetrician's/neonatological aspect, ignoring all recent new microbiological discoveries concerning gonorrhea within his papers published in 1881 [19, 20], 1883 (here the "Micrococcus Neisser" is only mentioned in one short sentence as most probable pathogenic agent for gonorrheal ophthalmia neonatorum [21]) and 1884 (in English [23]). The author has never seen such a focused, condensed and straightforward approach without any scientific detour from the streamlined intentions as that performed by Crede.

Crede additionally recognized that the midwives were the central persons/institution for rapidly spreading this prophylactic regimen to hospitalized patients/deliveries and outpatients. This led to a high degree of controversies with his colleagues as many of them realized this as a form of undermining the authority of the physician and obstetrician. Crede wrote two outstanding books for midwives, where the aspect of ophthalmia neonatorum was also included [36, 37]. Further, demonstrating his positive attitude towards the responsibilities of midwives, Crede became appointed "Nestor of German midwifery" [8]. This reflects that Crede had no concerns regarding a potential conflict of interests and/or competence between physicians/obstetricians and midwives.

By this pragmatic, clinical, non-academic, and consequent way, by 2 years after Crede's first publication on prophylaxis of ophthalmia neonatorum ([19]; 1881), his prophylaxis became enforced by law for clinical deliveries in Austria in 1883, which is highlighted in his 1883 publication [21]. Here Crede claimed that all countries should introduce his method and should enforce it by law [21].

His four publications on ophthalmia neonatorum all have the same title, are easy to read, clearly structured, and in most parts highly repetitive, and do not allow alterations of the suggested prophylactic regimen. For today's understanding they appear almost like a guideline or kind of a directive.

Even the famous ophthalmologist Lucien Howe (1848-1928) [38] was so impressed by this approach that he established it in the "New World". Nevertheless, he used a weaker concentration of 1% silver nitrate as did many other physicians and countries by law. In addition, silver acetate was used alternatively instead of silver nitrate in many places [39].

In summary, Crede made a great contribution to mankind, broadly "enforcing" the eye prophylaxis against gonorrheal ophthalmia neonato-rum within 2 years without spending any unnecessary time for the final "i-dot" of optimization of this technique.

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