A natural treatment for an antibiotic-resistant bacterial infection that causes blindness in infants can be effectively administered through a simple eye drop without causing irritation, Kingston University London researchers have found.
Neisseria gonorrhoeae, the bacteria which causes the sexually-transmitted infection gonorrhea, is increasingly becoming resistant to the antibiotics used to treat it.
The infection can be passed from a pregnant woman to her baby, where it can infect the eyes and cause permanent blindness if left untreated.
A research team from Kingston University has been exploring the potential of antimicrobial agent monocaprin as an alternative to antibiotic treatments for gonorrhea infections.
The experts believe it has the potential to help combat both the growing threat of antibiotic resistance and provide a cheap, easy-to-produce remedy in parts of the world where medication is harder to access.
“As antibiotics become less effective against circulating strains of the bacteria as a result of antimicrobial resistance, alternative treatments are becoming increasingly important to the future of global healthcare,” Associate Professor Dr. Lori Snyder, from the Faculty of Science, Engineering and Computing at Kingston University, said.
“Our research has been focused on finding a low-cost, easily accessible treatment the bacteria is unlikely to become resistant to.”
Monocaprin is a monoglyceride – a modified fatty acid – and the research team has previously demonstrated its effectiveness at killing Neisseria gonorrhoeae.
Now, in findings published in the journal Scientific Reports by Nature Research, the team has shown how it can be administered in an eye drop formulation without causing irritation.
“In monocaprin, we’ve found a powerful agent that can clear infections in the eye as well as acting as a preventative treatment,” Dr. Snyder said. “Some of the other alternatives proposed to use against this bacteria have been found to cause irritation and are only useful as a preventative measure, not a treatment.
We’ve come up with a thickened eye drop that keeps the treatment on the surface of the eye for long enough to be effective, using components that are readily available. The eye drop doesn’t need to be stored in special conditions – it stays stable for long periods and, importantly, it doesn’t cause discomfort to the eye.”
While the formulation has so far only been tested on bovine eyes sourced from abattoirs, the next step will be to move to human trials. The team is also looking at natural products high in monocaprin and how the antimicrobial agent can be released from them as part of research into ensuring the treatment can be manufactured quickly and easily around the world.
The monocaprin eye drop was an example of how materials derived from nature could be repurposed to combat a range of conditions currently treated through antibiotics, Professor Raid Alany, a pharmaceutics expert who worked on the formulation with Dr. Snyder, said.
“Once we had identified this candidate as effective in the test tube, the challenge was how to overcome the issues around solubility of fatty acids to convert it into an eye drop that could be administered to a child,” he said.
“Now we have done that, the next step will be to prove it can work in a living human eye. If that’s successful, we can look at working with manufacturers to hopefully bring this treatment to patients around the world in the near future.”
From a public health point of view gonococcal ophthalmia neonatorum (GCON) is important as it can rapidly lead to blindness. The frequency of GCON is determined by the prevalence of maternal gonococcal infection.
In most industrialized countries the prevalence of gonorrhoea in pregnant women is less than 1 %; in developing countries the rates are between 3% and 15%, more than 50% being due to penicillinaseproducing Neisseria gonorrhoeae strains (PPNG). The rate of transmission from mother to newborn is between 30% and 50%.
Strategies for the control of GCON include: (1) prevention of gonococcal infection in women of childbearing age, (2) detection and treatment ofgonococcal infection in pregnant women, (3) eye prophylaxis in the newborn at birth, and (4) diagnosis and treatment of GCON. Eye prophylaxis by the instillation immediately after birth of either 1% silver nitrate eye drops or 1% tetracycline eye ointment is very effective.
This reduces the GCON incidence by 80% to 95% and is highly cost-effective, particularly in high-risk settings.
Gonococcal Infections
Prevalence In pregnant women. Data on the prevalence of gonorrhoea among women receiving antenatal care give an estimate of the potential complications in puerperal women and neonates. Table 2 summarizes the prevalence of gonorrhoea in pregnant women from surveys in different countries.
The reported prevalence from the USA shows wide geographical variations ranging from 0.6% to 7.6% in the different popula tions studied. Generally, much higher prevalence rates were observed in populations in the USA than in other industrialized countries where they are usually below 1%.
In most African countries the prevalence rates among antenatal clinic patients range from 3% to as high as 22%.
The few published results from other continents suggest that some but not all countries have a prevalence rate similar to that in Africa.
Since the mid-1970s, worldwide dissemination of penicillinase-producing N. gonorrhoeae (PPNG) strains and of strains with chromosomally-mediated penicillin and tetracycline resistance increased progres sively. The proportion of gonococcal infection due to PPNG strains is summarized in Table 3, which shows the need for new approaches to gonorrhoea therapy.
Transmission rate from mother to baby.
The neonate acquires GCON during delivery through the infected birth canal. Occasionally the disease has been trans mitted to infants delivered by Caesarian section after prolonged rupture of the membranes (27).
The transmission rate from mother to child in the absence of ocular prophylaxis has been estimated in two prospective studies in Africa (Table 4). In Kenya (Nairobi) GCON developed in 28 out of 67 babies whose mothers had N. gonorrhoeae infections, a trans mission rate of 42% (seven babies were lost for follow-up), while in Cameroon, 30% of exposed babies (12/40) developed GCON; the incidence rates are therefore 3.6 and 4 per 100 live births, respectively.
These incidence rates are very high, compared with those from Western countries (average, 0.06%). Asymp tomatic carriage of N. gonorrhoeae in the eyes with minimum inflammation has been described (23). In the above-mentioned studies from Africa no children were identified with an asymptomatic gonococcal infection in the eyes.
The study from Kenya demonstrated that the transmission rates of PPNG and non-PPNG strains were similar. When the mother is infected with both N. gonorrhoeae and C. trachomatis at the same time, the gonococcal transmission rate to the newborn is significantly higher (68% instead of 31%, P < 0.01) (17).
This study also showed that postpartum endo metritis in the mother was a significant risk factor for GCON which may be explained by differences in pathogenicity of the strains, by both conditions arising from maternal chorioamnionitis, or by factors protect ing the mothers against postpartum upper genital tract infection which might also protect the newborns against ocular infection.
Conjunctiva) infection is the commonest clinical form of N. gonorrhoeae infection in the newborn, but the mucous membranes of the vagina, the pharynx, the rectum and the ear canal may also be colonized. Isolation rates of N. gonorrhoeae from the pharynx in neonates with gonococcal ON range from 7% to 15% (10, 17).
The transmission rate of N. gonorrhoeae from the maternal cervix to extraocular sites has never been determined in the absence of GCON and the natural history of extra-ocular gonococcal infection is unclear. The possibility of extra-ocular colonization of N. gonorrhoeae in infants with gonococcal ON has thera peutic implications and GCON should therefore always be treated systemically.
reference link https://www.researchgate.net/publication/20544188
Antibiotic-resistant gonorrhea is now a reality, as well as the consequences of untreatable infections. Gonococcal eye infections result in blindness if not properly treated; they accounted for the vast majority of infections in children in homes for the blind in the pre-antibiotic era. Neisseria gonorrhoeae infects the eyes of infants born to mothers with gonorrhea and can also infect the eyes of adults. Changes in sexual practices may account for the rise in adult gonococcal eye infections, although some cases seem to have occurred with no associated genital infection.
As gonorrhea becomes increasingly difficult to treat, the consequences for the treatment of gonococcal blindness must be considered as well. Monocaprin was shown to be effective in rapidly killing N. gonorrhoeae, and is non-irritating in ocular models. Repeated passage in sub-lethal monocaprin induces neither resistance in gonococci nor genomic mutations that are suggestive of resistance. Here, we show that 1 mM monocaprin kills 100% of N. gonorrhoeae in 2 min, and is equally effective against N. meningitidis, a rare cause of ophthalmia neonatorum that is potentially lethal.
Monocaprin at 1 mM also completely kills Staphylococcus aureus after 60 min, and 25 mM kills 80% of Pseudomonas aeruginosa after 360 min. Previously, 1 mM monocaprin was shown to eliminate Chlamydia trachomatis in 5 min. Monocaprin is, therefore, a promising active ingredient in the treatment and prophylaxis of keratitis, especially considering the growing threat of gonococcal blindness due to antimicrobial resistance
Anti-Gonococcal Properties of Monocaprin
Recently, we showed that monocaprin is a promising antimicrobial agent with the potential for use against gonococcal ophthalmia neonatorum [29–31]. Monocaprin is the monoglyceride of the fatty acid, capric acid. The antimicrobial activity of monocaprin was previously demonstrated against the N. gonorrhoeae strain, NCCP11945, and against several clinical isolates, killing gonococci at a concentration of 1 mM in 2 min [30].
Repeated passage of gonococci on media containing a sub-lethal concentration of monocaprin neither induced resistance nor genomic changes indicative of resistance arising [31]. The antimicrobial activity of monocaprin was demonstrated for other species, including efficacy against Chlamydia trachomatis at a concentration of 1 mM in 5 min [32].
In this short communication, we demonstrate the effectiveness of monocaprin against other bacteria capable of causing eye infections in infants and adults.
reference link : DOI: 10.3390/antibiotics7030059
More information: Colin P. Churchward et al. Monocaprin eye drop formulation to combat antibiotic resistant gonococcal blindness, Scientific Reports (2020). DOI: 10.1038/s41598-020-68722-8
