Shuɗin methylene da Bartonella: sakamakon dakin gwaje-gwaje da iyakokin shaidar asibiti

Farantin reno da mara lafiya suna da kalma ɗaya a tarayya, kamuwa da cuta, amma ma’anarta ba ɗaya ba ce a wuraren biyu. A farantin, kamuwa da cuta yana nufin ƙidayar tarin ƙwayoyin cuta a kan agar. A mara lafiya kuwa, yana nufin ƙwayoyin cuta a cikin ƙwayoyin halitta da jijiyoyi, magunguna da ke tafiya cikin jini da nama, da tsarin garkuwar jiki da ke yin wani ɓangare na aikin. Idan aka gauraya waɗannan biyun, adadi mai ban mamaki daga dakin gwaje-gwaje zai fara kama da hanyar magani. Idan aka ware su, wannan adadin zai zama abin da yake a zahiri: dalilin yin gwaji na gaba.

Wannan bambancewa ita ce babbar manufar wannan bita kan shuɗin methylene da Bartonella. Nazarin dakin gwaje-gwaje guda biyu daga ƙungiyar bincike ɗaya sun gwada shuɗin methylene kan Bartonella henselae a yanayin da ba ta girma. Dukansu sun ba da rahoton tasiri mai ƙarfi a cikin kwantena na gilashi da roba. Babu wanda ya gwada shi a kan mutum.

Dalilin da masu bincike ke gwada matakin tsayawar girma

Yawancin gwaje-gwajen maganin ƙwayoyin cuta suna amfani da ƙwayoyin halitta masu girma. Wannan samfurin gwaji yana barin wani yanayi mafi wahala a baya: ƙwayoyin halitta da suka daina rarrabuwa kuma suke jure magungunan da ke kashe takwarorinsu masu girma.

Bartonella na iya dawwama a jiki, ciki har da cikin jajayen ƙwayoyin jini da ƙwayoyin halittar da ke lulluɓe cikin jijiyoyi. Saboda haka ƙungiyar ta tambayi waɗanne magunguna da aka amince da su za su iya kashe B. henselae bayan ta shiga matakin tsayawar girma. Ƙaramin MIC kan ƙwayoyin halitta masu girma bai iya hasashen kashe waɗanda ke matakin tsayawar girma ba. Rifampin yana da MIC mai ƙanƙanta sosai, amma bai kashe ƙwayoyin halittar da suka tsaya girma sosai ba, yayin da sinadarai masu MIC mafi girma suka kashe su sosai. Masu karatu da ke son wata hanya ta gaba ɗaya don karanta irin wannan takarda za su same ta a jagorar karanta binciken shuɗin methylene.

Gwajin tantancewa na farko: Li da abokan aiki, 2019

Gwajin tantance matakin tsayawar girma na 2019 a Antibiotics ya yi amfani da nau’i ɗaya, B. henselae JK53, wanda aka reno a matsakaicin reno na Schneider tare da 10 percent na ruwan jinin ɗan tayi na shanu a 37 C tare da 5 percent CO2. Renon kwana ɗaya ya ƙunshi galibi ƙwayoyin halitta masu rarrabuwa da suka watse. An ɗauki renon kwana biyar, mai kusan 10 zuwa ƙarfin 8 na raka’o’in samar da tarin ƙwayoyin cuta a kowane mL, a matsayin matakin tsayawar girma, kuma ya ƙunshi dunƙulen ƙwayoyin halitta da ake iya gani.

An yi gwajin da SYBR Green I tare da propidium iodide, an kuma daidaita shi ta amfani da gaurayen ƙwayoyin halitta masu rai da waɗanda aka kashe da isopropanol. Saboda shuɗin methylene yana da launi mai ƙarfi, an tabbatar da sakamakon sinadaran da suka nuna tasiri ta amfani da madubin ƙara girma, sannan ta ƙidayar tarin ƙwayoyin cuta a kan agar mai jini, wanda ya fi tsauri a matsayin ma’aunin ƙarshe.

Daga magunguna 1,581 da aka amince da su a 50 micromolar, shuɗin methylene ya bar 16 percent masu rai bisa na’urar karanta faranti, da 25 percent bisa madubin ƙara girma. Daptomycin ya bar 21 percent, azoles da dama sun bar 22 zuwa 27 percent, gentamicin 32 percent, erythromycin 66 percent, ciprofloxacin 74 percent. Pyrvinium pamoate ya nuna tasiri mafi ƙarfi a na’urar karantawa, amma ba a iya tantance shi ta madubin ƙara girma ba saboda hasken fluorescence nasa.

Kan B. henselae mai girma, MIC na shuɗin methylene ya kasance 0.08 zuwa 0.16 micrograms per mL. Kan ƙwayoyin halitta na renon kwana biyar da suka tsaya girma, a 5 micrograms per mL, ƙidayar tarin ƙwayoyin cuta ta ragu zuwa babu tarin da ake iya ganowa bayan kwana ɗaya na fallasawa. Wannan ya yi daidai da daptomycin da pyrvinium pamoate a matakan tattarawar da aka gwada su. Wani gwaji dabam na kashe ƙwayoyin cuta a kan lokaci ya yi amfani da 10 micrograms per mL. Waɗannan matakan fallasawa ne na dakin gwaje-gwaje, ba adadin maganin da za a ba mutum ba, kuma takardar ta bayyana su haka. Wata ƙimar kololuwar tattarawa a plasma na ɗan Adam da aka ambata, kusa da 3.9 micrograms per mL, ta bayyana a takardar ne kawai a matsayin bayanin mahalli. Bayanin yadda shuɗin methylene ke tafiya a jiki ya bayyana dalilin da ba za a ɗauki adadin plasma a matsayin adadin da ke cikin nama ba.

Takardar ta bayyana iyakoki biyu a fili. Babu samfurin gwaji na biofilm, kuma babu gwajin haɗa shuɗin methylene da wasu magunguna. Dunƙulen kwana biyar tarin ƙwayoyin halitta ne a renon ruwa da ya tsaya girma, ba gwajin biofilm da aka tabbatar da ingancinsa ba. Marubutan sun nemi a yi bincike a kan dabbobi, haɗaɗɗun magunguna, biofilm, da wasu jinsunan Bartonella.

Haɗaɗɗun magunguna da ƙwayoyin halitta da aka samo daga biofilm: Zheng da abokan aiki, 2020

Nazarin bibiyar na 2020 a BMC Microbiology ya riƙe nau’in ƙwayar cuta da matsakaicin reno iri ɗaya, amma ya koma renon kwana shida da ya tsaya girma, ya kuma ƙara abubuwa biyu da takardar farko ba ta da su: haɗaɗɗun magunguna biyu da samfurin gwaji na ƙwayoyin halitta da aka samo daga biofilm.

Ga magungunan da aka gwada ɗaya-ɗaya a matakin 5 micrograms per mL iri ɗaya na tsawon awa 24, shuɗin methylene ya bar 3.2 ninki 10 zuwa ƙarfin 4 na raka’o’in samar da tarin ƙwayoyin cuta a kowane mL, idan aka kwatanta da samfurin kwatance mai kusan 2.8 ninki 10 zuwa ƙarfin 10. Ciprofloxacin, gentamicin, da nitrofurantoin sun bar tarin ƙwayoyin cuta mafi kaɗan a wannan lokacin. Wannan ya bambanta da sakamakon 2019, inda matakin da aka ayyana iri ɗaya ya ba da babu tarin ƙwayoyin cuta da ake iya ganowa bayan kwana ɗaya. Shekarun reno, yawan ƙwayoyin halitta a cikinsa, da yadda aka sarrafa shi sun bambanta. Saboda haka an iya maimaita sakamakon kashe ƙwayoyin cuta a gaba ɗaya, amma ba da ƙarfin tasiri iri ɗaya ba. Wannan bambancin daga gwaji zuwa gwaji yana cikin dalilan da binciken aminci da mu’amalar magunguna na yau da kullum ke ɗaukar ƙarfin tasiri a dakin gwaje-gwaje a matsayin abu dabam da tasirin da ake samu a asibiti.

Gwajin tantance haɗaɗɗun magunguna shi ne ɓangaren da aka fi ambata. An sa kowane magani a 5 micrograms per mL. Haɗin azithromycin da shuɗin methylene da haɗin rifampin da shuɗin methylene duk sun ba da babu tarin ƙwayoyin cuta na matakin tsayawar girma da ake iya ganowa a awa 24. Haka ma haɗaɗɗun ciprofloxacin guda biyu, kuma waɗannan huɗu kaɗai ne daga cikin haɗe-haɗe 25 da aka gwada suka yi haka. Ba a yi nazari na ƙa’ida kan tasirin ƙarfafa juna ba, don haka kalmar da ta dace ita ce haɗin magunguna mai aiki a ƙarƙashin waɗannan sharuɗɗan, ba tasirin ƙarfafa juna da aka tabbatar ba.

Gwajin biofilm ya gwada ƙwayoyin halitta da aka samo daga ƙaramin biofilm da aka tarwatsa, ba shiga cikin cikakken biofilm da ya balaga ba. An reno ƙwayoyin halittar na kwana biyar, an tsarma su a faranti masu ramuka na ƙarin kwana biyar, an tabbatar da su ta hanyar rini da crystal violet, sannan aka kankare su kafin fallasa su ga magunguna. A 5 micrograms per mL, adadin da shuɗin methylene shi kaɗai ya bari ya ragu zuwa 2.3 ninki 10 zuwa ƙarfin 2 a rana ta 6. Yana cikin magunguna ɗaiɗaikun da suka fi tasiri, amma bai kai sifili ba. Haɗaɗɗun shuɗin methylene guda biyu sun kai sifili a rana ta 6, haka ma haɗaɗɗun ciprofloxacin guda biyu.

Marubutan sun nuna irin iyakokin da mai karatu mai taka-tsantsan zai lura da su: ƙaramin biofilm da aka kankare maimakon tsohon biofilm da yake cikakke; matakin tattarawa guda ɗaya mai sauƙin amfani ga dukkan magunguna maimakon amfani da kowanne a kololuwar matakinsa da za a iya samu a zahiri; zaɓaɓɓun haɗe-haɗe kawai da suka dogara kan azithromycin ko rifampin; nau’in ƙwayar cuta ɗaya; babu dabbobi; babu marasa lafiya. An ba da shawarar binciken haɗa magunguna uku a nan gaba, ba a bayar da rahoton yin sa ba.

Kwatanta tsarin nazarin

Teburin ya taƙaita ainihin manufar wannan maƙala. Duk abin da ke hagu da shafin ƙarshe aikin reno ne. Babu wani abu a cikin kowace takarda da ya shiga shafin ƙarshe.

Bartonella ba Borrelia ba ce

Takardun biyu sun ambaci Borrelia burgdorferi, ƙwayar cuta mai siffar karkace da ke haddasa cutar Lyme, saboda gwajin rini ya samo asali ne daga aikin da aka yi a baya kan matakin tsayawar girma na Borrelia a wannan dakin gwaje-gwaje. A can ma, shuɗin methylene da daptomycin sun nuna tasiri a gwajin tantancewa. Wannan tarihin yana taimakawa wajen fahimtar mahalli, amma kuma yakan zama tushen kuskure.

Babu gwaji a kowace takardar Bartonella da ya gwada Borrelia tare da Bartonella gefe da gefe. Ƙwayoyin cutar sun bambanta, matsakaicin reno ya bambanta, matakan tattarawa sun bambanta, kuma an bayyana tasirin shuɗin methylene kan membrane na Bartonella da ake hasashe a matsayin zato da ke buƙatar ƙarin bincike. Bai kamata a ɗauki sakamakon wani jinsi a yi amfani da shi ga wani ba, kuma babu takardar da ke goyon bayan iƙirari masu faɗi game da ƙwayoyin cuta masu rayuwar dogaro da wani. Saboda wannan dalili, kwatanta ƙwayoyin Borrelia da Bartonella masu dawwama yana ware wallafe-wallafen binciken biyun.

Dalilin da sakamakon reno ba ya zama tsarin magani

Ana iya fahimtar sha’awar neman tsarin maganin Bartonella da shuɗin methylene. Waɗannan takardun su ne dalilin da ya kamata a ɗauki wannan magana a matsayin alamar gargaɗi maimakon jerin abubuwan saye.

Na farko, 5 micrograms per mL a ramin farantin gwaji ba umarnin magani ba ne. Ba ya ƙunshe da bayanai kan shigar magani jiki, yaɗuwarsa, ɗaurewarsa da furotin, shigarsa cikin ƙwayoyin halitta, ko yadda jiki zai iya jure shi. Marubutan sun zaɓe shi a matsayin matsakaicin ƙiyasin kololuwar tattarawar magungunan ƙwayoyin cuta, kuma sun ce binciken gaba ya kamata ya yi amfani da kowane magani a matakin da za a iya samu a zahiri.

Na biyu, sifili na tarin ƙwayoyin cuta yana nufin babu tarin a ƙarƙashin waɗancan sharuɗɗan dasawa, ba cewa nama ya kuɓuta gaba ɗaya daga ƙwayoyin cuta ba. Ƙwayoyin cuta masu dawwama, ƙwayoyin cuta da ke cikin ƙwayoyin halitta, da iyakokin ɗaukar samfuri duk ba sa cikin abin da farantin agar ke wakilta.

Na uku, haɗaɗɗun magunguna da ke kawar da ƙwayoyin cuta a ramin farantin gwaji na iya kasa aiki ko su cutar a jiki. Azithromycin da shuɗin methylene, da rifampin da shuɗin methylene, haɗe-haɗen dakin gwaje-gwaje ne a matakan fallasawa na dakin gwaje-gwaje. Idan babu bayanan yadda magungunan ke tafiya a jikin dabbobi da bayanan gwajin ɗan Adam mai tsari, babu adadin magani, babu tsawon lokacin amfani, kuma babu ma’aunin amfanin da za a samu idan aka kwatanta da haɗari. Duk wanda ke nazarin zaɓuɓɓuka ya kamata ya tattauna su da ƙwararren likita, ya kuma duba lokacin da amfani da shuɗin methylene ke buƙatar kulawar likita kafin ya yanke wata matsaya daga bayanan farantin gwaji.

Ƙaramin sakamakon da waɗannan takardun suke goyon baya shi ne: shuɗin methylene yana da tasirin da za a iya maimaitawa kan B. henselae JK53 da ba ta girma a wajen jiki, ciki har da haɗaɗɗun magunguna biyu a dakin gwaje-gwaje. Sakamakon haɗaɗɗun magunguna da ƙwayoyin halitta da aka samo daga biofilm mafi ƙarfi ya fito ne daga nazarin 2020. Duk sauran abubuwa, ciki har da ko wannan tasirin yana da muhimmanci ga bartonellosis a ɗan Adam, har yanzu ba a gwada su ba.