Transient Bacteremia Caused by Atopobium Vaginae After Caesarean Delivery : Case Report

Introduction: Genital microbiome of woman is still a puzzle to this day. It consists of a large number of diff erent bacterial species and phenotypes that make up the normal genital fl ora, while in the cases of its change there is a predominance of certain, especially anaerobic species, which is the case with bacterial vaginosis. These types are mostly rare causing invasive infections, but under certain conditions can lead to severe infections, such as multiple parts of the genital tract, and to an unwanted outcome in the pregnancy. Case report: This paper presents an extremely rare case of transient bacteremia caused by Atopobium vaginae type in a patient following a cesarean section where empirical therapy gave a positive eff ect and the patient recovered and released home with healthy newborn. Conclusions: During the clinical work it is important to be aware of the diff erent anaerobic species present in the genital tract of women microbiome like Atopobium vaginae and should adjust the empirical therapy, which was the case here.


INTRODUCTION
Cesarean section (SC) as a method of delivery has greatly contributed to the improvement of perinatal outcome.Th e number of SCs is steadily increasing.Th e death outcome of women in reporting is today a rarity, and newborns are better fi t for post-natal life.On the other hand, SC as a surgical intervention follows a number of problems, such as an increase in the number of thromboembolic complications and an increased risk of developing infections, septic conditions and bacteremia [1][2][3].
Bacteremia is defi ned as the presence of alive bacteria in the bloodstream.Bacteremia could be primary, where bacteria enter the bloodstream directly or secondary by entering in the bloodstream from another body site (wounds, respiratory tract, gastrointestinal tract, bladder, genital tract).By the timing of bacteria presence in the bloodstream, bacteremia can be defi ned as transient where bacteria are present for a minutes to a few hours, intermittent where bacteria is present periodical by existing an infection elsewhere in the body or as persistant.Bacteremia as clinical condition diff er from sepsis where bloodstream infection is associated with serious infl ammatory response, untreated lead even to the death.Bacteremia in this population is mostly associated with earlier gestational age, lower birth weight, and chorioamnionitis [1][2][3][4].
Up today there is no suffi cient data about transient bacteremia aft er SC.Th e most cases descriebed were sepsis coused by mostly aerobic bacteria and small percent by diff erent anaerobic species.
Only one case of transient bacteremia caused by Atopobium vaginae has been described in the literature so far, and only two cases of sepsis caused by other Atopobium species [5,6].

THE AIM
Th e aim of this paper is to point out the occurrence of postpartum transient bacteremia aft er the SC caused by unexpected, rare bacterial species found in the genital tract of the woman.

CASE REPORT
A 34 years old woman in 39 th week of pregnancy was admitted at the Clinic for gynecology and obstetrics of the Clinical Center of Serbia to be prepared for the delivery.Th e patient was in a good general condition.Th e presence of diabetes mellitus in pregnancy (DMG) and thrombophilia, a genetically confi rmed mutation for the plasminogen activator inhibitor (PAI 1) 4G / 4G is recorded according to anamnesis and is based on provided documents.During the examination condylomas of the vulva and perineum were detected (Condylomata accuminata vulvae et perinea).Th e position of the fetus was ad pedem.
Due to the presence of condylomas and ad pedem fetus position it was decided to deliver a baby with SC.
In accordance with the routine procedure before cesarean section samples of cervical and vaginal swabs were obtained, urine, for bacteriological analyzes, blood for blood typing, biochemical analysis, complete blood count, C-reactive protein (CPR), and screening of hemostasis tests.All hematological and biochemical blood tests were within the reference range.
Th e patient was blood group A, RhD positive.Since it was decided perform the delivery via SC, one unit of leukodepleted packed red blood cells was crossmatched.
Pathogenic bacteria were not isolated from genital swabs.On the direct microscopic smear, colored with standard Gram stain a small number of lactobacilli were found, "Clue -cells" free.Th e bacteriological result of urin sample, in the context of SC preparation, was sterile.
SC was performed in total anesthesia and on that occasion a healthy female newborn in 39 weeks of gestation was born, with birth weight of 3200 grams, a body length of 51 cm, a head circumference of 34 cm and Apgar score 9 and 10 in the fi rst and fi ft h minutes respectively.
Th e bacteriological uterine swab, also performed at the Clinic as a routine procedure at the SC, was sterile.
An antibiotic from the group of aminoglycosides, Amikacin® (amikacin, solution for injection / infusion, 500 mg, ampoule, Galenika AD, Serbia), 1g / 24h is added two days aft er the SC in therapy, administered in the same infusion manner by ceft riaxone and metronidazole to act as a triple antibiotic therapy.In addition, antithrombotic prophylaxis and supportive therapy have been continued.
In the post-operative period, the patient is afebrile, the leukocytes are normalized and achieve a value of 10. 20x10e9 / L. However, the CRP value is 191.Blood cultures were incubated for fi ve days in an automated blood culture system BactAlert apparatus (BioMerieux, France), according to the manufacturer's recommendation and according to the most commonly isolated pathogens typical for this population of patients.
Concerning targeted samples sent for bacteriological analysis, Enterococcus spp. was isolated from the swab of lochia in a small number, the cervical and vaginal swabs culture remained sterile.In a direct microscopic Gram smear the presence of a small number of lactobacilli and a small cocobacillary form of bacteria was found.Staphylococcus spp.coagulase negative was isolated from the wound swab.ronidazole in the same previously administered dose.Other therapy administered to patient involved Chymoral forte (trypsin / chymotrypsin combinations, 100,000 Armory units (AI), gastro-resistant tablet, Galenika, a.d.Serbia) 3x2, Novalgetol ampoule 1 daily as needed and probiotic 2x1.Th e dose of Fraxiparin due to a low preventive level (anti-Xa = 0. 15 IU / ml) was increased to 0.4 ml / 12 h.Following two days of administered therapy, from the wound swab was again isolated Staphylococcus spp coagulase negative, while the lochia swab culture remained sterile.Th e patient remains on the same antibiotic therapy in the following days.Aft er fi ve days under the same antibiotic therapy, the bacterial swabs of the wound and the abdominal puncture remained sterile and the CRP values fell (Fig. 1.).
In the blood culture set, sampled in the second phase of fever, on the fi ft h day aft er the start of its incubation, the apparatus detected the presence of bacterial elements in the anaerobic bottle.In a direct microscopic smear colored with standard Gram stain, from the positive anaerobic bottle in which the apparatus detected the growth of the pathogen, the presence of Gram positive coccobacilli was deployed individually, in pairs or shorter chains.Positive anaerobic bottle is sub-cultivated to conventional anaerobic and aerobic media.Media incubated under aerobic conditions remained sterile, while on media incubated under anaerobic conditions aft er 48 hours the growth of bacterial elements was detected.Gram positive coccobacillus were noticed by standard Gram stain.
Identifi cation of the isolated pathogen to the level of the species was done on the VITEK 2 Compact apparatus.In this case, a bacterial species of Atopobium vaginae was identifi ed with a probability of 90%.However, the device did not determine the antimicrobial sensitivity of the identifi ed pathogen.
Th e other two sets of blood cultures were negative, without the presence of a pathogen.

DISCUSSION
Infections caused by bacteria Atopobium vaginae occur rarely and generally occur aft er gynecological invasive interventions and procedures.Th ey have been described in the case of a tubo-ovarial abscess occurring in the case of transvaginal detection of the oocyte, and it has recently been described in the case of endometriosis [7][8][9].
Atopobium vaginae was discovered in 1999.Until 2004, these strictly anaerobic In the second set of blood culture the bacterial species Atopobium vaginae was isolated, strictly anaerobic Gram-positive bacteria requiring longer incubation period for its increase.
Certainly, molecular methods are golden standards for the precise determination of species [7], however, in our case, based on the fi nding of direct microscopic smear, it can be suspected that a patient had an intermediate stage of bacterial vaginosis in which isolated species was identifi ed on VITEK 2 Compact apparatus and whose presence is found in around 80% of changed vaginal microbioma [13].
According to the European Committee on Antimicrobial Susceptibility Testing (EUCAST), the susceptibility of anaerobic bacteria to antimicrobial drugs is exclusively determined by the method of determining minimal inhibitory concentration (MIC) [15] VITEK 2 Compact apparatus did not specify the MIC for the identifi ed bacterial species, which happens if the inoculum of the bacteria is not suffi ciently dense.
Th e most commonly used antibiotic in anaerobic bacterial species is metronidazole.According to available literature data, the results of the Atopobium vaginae susceptibility testing on metronidazole are controversial, due to the fact that some types have high MIC values.Although, some authors believe that this bacteria has instrinsic resistance to this antibiotic, but some examiners confi rmed the susceptibility of the tested isolates of Atopobium vaginae to metronidazole.However, clindamycin is recommended for successful treatment [13,14].
Th e susceptibility to diff erent groups of antibiotics with diff erent mechanisms of action must certainly be determined by MIC.In all previous studies the susceptibility of this bacterial species to vancomycin was found, where the MIC is about 1.5 μg / ml and according to the EUCAST standard from the year 2018 it belongs to the susceptibility zone for Gram-positive anaerobic bacilli (S2 ≤2 μg / ml; R ≥2 μg / l) not including Clostridium diffi cile [15,16].
Up to now, one case of Atopobium vaginae isolated from blood culture has been described in the any research paper as a transient bacteremia in a patient who underwent gynecological invasive intervention during pregnancy, transcervical sampling of cho-Gram positive coccobacilli were considered as normal bacterial fl ora of the women's vagina [10].Th e change in the physiological fl ora of the vagina, dysbiosis, or generally altered normal ecosystem of the vaginal microbiome is characterized by a reduced number of lactobacilli.Th e most common dysbiosis is bacterial vaginosis that, in addition to the absence of a small number of lactobacilli, is characterized by the presence of a large number of diff erent anaerobic species, some of which are specifi c for this condition.Today it has been proven that Atopobium vaginae is found in over 90% of cases in women with bacterial vaginosis and about 80% in its intermediate phase.Bacterial vaginosis is also oft en associated with other sexually transmitted pathogens: Mycoplasma hominis, Ureaplasma urealyticum/parvum, Chlamidia trachomatis, rarely with Neisseria gonorrhoeae and other pathogens of viral etiology [11][12][13].
So far, a small number of studies have been concerned with the composition of the vaginal microbiome during pregnancy and before delivery.Vaginal microbiome is stable in most cases.Qualitative studies based on the analysis of conventional culture have determined several hundred diff erent phenotypes in the composition of vaginal microbials that are constantly or occasionally present [13].
In our patient, according to the "Nugent-score" criteria for the detection of bacterial vaginosis on a direct microscopic examination can indicate the intermediate phase of bacterial vaginosis.Bacterial vaginosis can lead to premature delivery or premature rupture of the fetuses membranes [14].In addition to the above-mentioned risk factors in pregnancy, this condition is also associated with a higher susceptibility to pathogens belonging to sexually transmissible, which was also the case in our patient having genital condylomas caused by Human papilloma virus (HPV) [12][13][14].Condylomas are one of the indications for the SC delivery.
No pathogen was identifi ed that would be signifi cant from genital samples and urine samples sent to bacteriological analysis as a regular medical procedure and from targeted samples in the period of increased markers of the infl ammatory reaction.All isolated bacterial species were conditionally pathogenic, and empirical therapy and targeted therapy have been proven to be adequate aft er the antibiotic sensitivity assessment.rionic ducts by procedures and prescribed guides, without complications [7].Th e case of sepsis caused by other Atopobium species is described in patient with fulminant Fournier's gangrene admitted to the hospital due to a perianal abscess that spontaneously drained for a week [5].

CONCLUSION
Tgenital microbial fl ora of women is composed of over 300 diff erent species, and some of them can cause serious infections in certain situations.If the patient during the postpartal period was febrile and with septic symptoms, it is important to be aware of the diff erent anaerobic species present in the genital tract of women microbiome, like Atopobium vaginae, and should adjust the empirical therapy, which was the case here.

Volume 5 •
5mg / L. Aft er 6 days of hospital stay, due to elevated CRP values and body temperature, three sets of blood cultures in aerobic and an-656 Number 2 • May 2018 • HOPH aerobic bottles were sampled successively.

Figure 1 .
Figure 1.Serum CRP decrease after the introduction of Vancomycin-MIP® therapy CRP -C-reactive protein