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EVIDENCE-BASED ANTIBIOTIC MANAGEMENT OF ACINETOBACTER
BAUMANNII MULTIDRUG-RESISTANT INFECTION- A SYSTEMATIC REVIEW
G eg Andie M. Ba buena1
B idge h Joy G. Bayani1
Mike Jhon M. Pedido1
C ys al Jane Da. Ped ano1
Gecelene C. Es o ico1’2
Ci il and Allied Depa men ; Chemical Technology and En i onmen al Science Depa men
1Technological Uni e si y o he Philippines – Taguig Ci y, Me o Manila 1630, Philippines
2De La Salle Uni e si y – Dama iñas, DBB-B, 4115 Wes A e., Dama iñas
ABSTRACT
Mul id ug- esis an (MDR) Acine obac e baumannii has eme ged as a majo global heal h conce n due o i s
ema kable abili y o su i e in hospi al en i onmen s and de elop esis ance o mul iple an ibio ic classes. This
sys ema ic e iew syn hesizes e idence om 2015 o 2025 on he e icacy, sa e y, and clinical ou comes o a ious
an ibio ic egimens used in managing MDR Acine obac e baumannii in ec ions. A comp ehensi e sea ch ac oss
PubMed, ScienceDi ec , Scopus, Google Schola , and he Coch ane Lib a y iden i ied ele an s udies, which
we e sc eened and app aised using PRISMA 2020 guidelines. Findings e eal ha adi ional mono he apies such
as colis in and igecycline exhibi mode a e e icacy and signi ican oxici y, whe eas combina ion he apies—
pa icula ly colis in wi h i ampicin o ca bapenems—demons a e highe clinical cu e a es and educed
mo ali y. The no el side opho e cephalospo in ce ide ocol achie ed he bes ou comes, wi h clinical cu e a es
up o 80% and he lowes mo ali y (≈22.5%), a ibu ed o i s abili y o o e come β-lac amase–media ed esis ance
mechanisms. E idence s ongly suppo s he use o combina ion and no el egimens o e mono he apy o enhance
he apeu ic success and minimize oxici y. S eng hening an imic obial s ewa dship and con inuous su eillance
a e impe a i e o comba he g owing h ea o MDR Acine obac e baumannii and p ese e an ibio ic e icacy.
Keywo ds:
Acine obac e baumannii; mul id ug esis ance; an ibio ic he apy; ce ide ocol; colis in; combina ion he apy;
an imic obial s ewa dship; clinical ou comes; e idence-based medicine; β-lac amase esis ance
INTRODUCTION
Acine obac e baumannii has eme ged as one o he mos o midable pa hogens in heal hca e se ings,
pa icula ly in in ensi e ca e uni s (ICUs). Known o i s abili y o su i e in ha sh en i onmen s and acqui e
esis ance o mul iple an ibio ic classes, A. baumannii has become a majo cause o hospi al-acqui ed in ec ions
such as en ila o -associa ed pneumonia, bloods eam in ec ions, u ina y ac in ec ions, and wound in ec ions
(Howa d e al., 2012; Wong e al., 2017). The inc easing p e alence o mul id ug- esis an (MDR), ex ensi ely
d ug- esis an (XDR), and e en pand ug- esis an (PDR) s ains poses a signi ican h ea o global public heal h
(WHO, 2017).
T adi ional he apeu ic op ions such as ca bapenems, aminoglycosides, and luo oquinolones ha e los
e icacy due o widesp ead esis ance mechanisms, including β-lac amase p oduc ion, e lux pumps, and
al e a ions in memb ane pe meabili y (Peleg e al., 2008; Lin & Lan, 2020). In esponse, clinicians ha e u ned o
las - eso agen s such as colis in, igecycline, and combina ion he apies; howe e , eme ging esis ance o hese
agen s u he complica es ea men ou comes (Du an e-Mangoni e al., 2015; Ka akons an is & Gikas, 2020).
Consequen ly, e idence-based app oaches o an ibio ic managemen a e essen ial o op imize he apeu ic e icacy,
minimize oxici y, and p e en u he esis ance de elopmen .
This sys ema ic e iew aims o syn hesize cu en e idence on he an ibio ic managemen o mul id ug-
esis an A. baumannii in ec ions. Speci ically, i e alua es he clinical e ec i eness, sa e y p o iles, and ou comes
associa ed wi h di e en mono he apy and combina ion egimens. By in eg a ing ecen clinical da a and guideline
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ecommenda ions, his e iew seeks o suppo in o med decision-making in he managemen o MDR A.
baumannii and guide u u e an imic obial s ewa dship s a egies.
OBJECTIVES
To sys ema ically e iew and e alua e e idence-based an ibio ic managemen s a egies o mul id ug-
esis an (MDR) Acine obac e baumannii in ec ions in clinical se ings. To iden i y commonly used an ibio ics
and combina ion he apies employed in he ea men o MDR Acine obac e baumannii in ec ions. To assess he
clinical e ec i eness and pa ien ou comes associa ed wi h a ious mono he apy and combina ion egimens. To
compa e he e icacy and sa e y p o iles o las - eso an ibio ics such as colis in, igecycline, and sulbac am-based
he apies. To analyze he eme ging ends in an ibio ic esis ance mechanisms in luencing he apeu ic success
a es. To e alua e e idence-based ecommenda ions and an imic obial s ewa dship s a egies aimed a op imizing
ea men ou comes and minimizing esis ance de elopmen .
METHODOLOGY
The me hodological p ocess ensu ed a igo ous, e idence-based app oach o iden i ying, ea ing, and
in e p e ing da a on an ibio ic managemen o MDR Acine obac e baumannii. By in eg a ing s uc u ed da a
ex ac ion, c i ical quali y app aisal, and sys ema ic syn hesis, his e iew p o ides a comp ehensi e o e iew o
he cu en s a e o e idence suppo ing e ec i e an imic obial s a egies agains his challenging pa hogen.
A. LITERATURE SEARCH STRATEGY
A comp ehensi e and sys ema ic li e a u e sea ch was conduc ed o iden i y ele an s udies in es iga ing
an ibio ic managemen o mul id ug- esis an (MDR) Acine obac e baumannii in ec ions. The sea ch co e ed
s udies published be ween Janua y 2015 and Sep embe 2025, ensu ing inclusion o ecen indings ha e lec
cu en an imic obial esis ance ends and he apeu ic s a egies.
Elec onic da abases sea ched included PubMed (MEDLINE), ScienceDi ec , Scopus, Google Schola , and
he Coch ane Lib a y. The sea ch s a egy u ilized a combina ion o Medical Subjec Headings (MeSH) e ms and
ee- ex keywo ds ela ed o Acine obac e baumannii, an ibio ic he apy, and mul id ug esis ance. Boolean
ope a o s (“AND”, “OR”) we e applied o e ine sea ch p ecision.
The p ima y sea ch s ing used was:
(“Acine obac e baumannii” OR “A. baumannii”) AND (“mul id ug- esis an ” OR “MDR”) AND
(“an ibio ic he apy” OR “an imic obial managemen ” OR “combina ion he apy” OR “colis in” OR
“ igecycline” OR “ca bapenem” OR “sulbac am”).
Addi ional a icles we e iden i ied h ough manual e e ence sc eening o key e iews and included
s udies o ensu e no ele an li e a u e was missed. All eco ds we e impo ed in o Mendeley Re e ence Manage
o o ganiza ion, duplica e emo al, and sc eening.
Ti les and abs ac s we e independen ly e iewed by wo esea che s o assess eligibili y. A icles ha me
he inclusion c i e ia we e e ie ed in ull ex and e alua ed o ele ance and me hodological quali y. The en i e
p ocess was conduc ed ollowing PRISMA 2020 guidelines o ensu e sys ema ic and anspa en selec ion.
B. DATA TREATMENT
A e selec ion, all eligible s udies we e o ganized and coded o sys ema ic compa ison. The da a ea men
p ocess in ol ed se e al s eps:
Da a O ganiza ion: All ex ac ed in o ma ion was abula ed in Mic oso Excel, allowing s uc u ed compa ison
ac oss s udies. Da a ca ego ies included s udy design, loca ion, sample size, in ec ion ype, an ibio ic egimens,
and ou come measu es.
Da a Cleaning and Ve i ica ion: Each da ase was e iewed o comple eness, accu acy, and consis ency.
Duplica e en ies and con lic ing da a we e c oss-checked agains o iginal s udy sou ces. Missing in o ma ion was
labeled as “No Repo ed (NR)” and excluded om pooled analysis.
Da a Ca ego iza ion: S udies we e g ouped acco ding o:
• Type o an ibio ic egimen: mono he apy s. combina ion he apy
• An ibio ic class: ca bapenems, polymyxins, e acyclines, β-lac am/β-lac amase inhibi o s, no el
agen s (e.g., ce ide ocol)
Clinical ou comes: cu e a e, mo ali y, mic obiological e adica ion, ad e se e ec s
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Da a Quali y E alua ion:
• Randomized Con olled T ials (RCTs) we e assessed using he Coch ane Risk o Bias 2 (RoB 2)
ool.
• Obse a ional s udies we e e alua ed using he Newcas le–O awa Scale (NOS).
• Sys ema ic e iews/me a-analyses we e app aised h ough he AMSTAR 2 checklis .
S udies we e ca ego ized as high, mode a e, o low quali y, wi h only mode a e- o-high quali y
e idence included in he inal analysis.
C. DATA EXTRACTION AND INTERPRETATION
Da a in e p e a ion ollowed bo h quan i a i e and quali a i e app oaches:
Quan i a i e In e p e a ion:Whe e da a we e compa able ac oss s udies (e.g., mo ali y o cu e a es),
desc ip i e s a is ics such as pe cen ages, means, and anges we e calcula ed. In cases o su icien homogenei y,
pooled analyses o summa y compa isons we e made o iden i y he mos e ec i e an ibio ic egimens.
Quali a i e In e p e a ion:Fo he e ogeneous da a, a na a i e syn hesis was conduc ed. This in ol ed
hema ic ca ego iza ion o indings, emphasizing clinical ou comes, an ibio ic e icacy, and eme ging esis ance
pa e ns. Pa e ns we e compa ed ac oss geog aphic egions and in ec ion ypes o highligh di e ences in
ea men esponse and an ibio ic success a es.
Bias and He e ogenei y Conside a ion:Va ia ions in pa ien popula ions, in ec ion si es, s udy designs, and
dosing egimens we e acknowledged. Resul s we e in e p e ed in ligh o hese limi a ions o ensu e an objec i e
and e idence-based syn hesis.
All in e p e a ions we e e i ied by wo independen e iewe s o ensu e alidi y and educe subjec i e
RESULTS AND DISCUSSION
The esul s highligh a posi i e shi in ea ing mul id ug- esis an Acine obac e baumannii (MDR-AB)
in ec ions. Ce ide ocol p o ed o be he mos e ec i e, wi h high cu e a es (70–80%) and low mo ali y (20–
25%), making i a p omising op ion o challenging cases. Combina ion he apies, like Colis in + Ri ampicin, also
showed be e esul s han colis in alone, o e ing imp o ed cu e a es and lowe mo ali y. While olde ea men s
like Colis in mono he apy and Tigecycline we e less e ec i e, he o e all end poin s o newe an ibio ics and
combina ion he apies p o iding much be e ou comes. These indings sugges ha ongoing ad ancemen s in
ea men , especially wi h Ce ide ocol and o he combina ion op ions, a e helping o imp o e pa ien ou comes
and ackle MDR-AB mo e e ec i ely.
Table 1: Summa y o An ibio ic Regimens and Clinical Ou comes in MDR Acine obac e baumannii
In ec ions (2015–2025)
Table 1 a ailabili y o ce ide ocol, hei s udy emains a pi o al e e ence documen ing he ad an ages and
limi a ions o combina ion he apy du ing ea lie phases o inc easing an imic obial esis ance. Complemen ing
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hese indings, Ka akons an is and Gikas (2020) explained how i ampicin, when used alongside colis in, can
pa ially ci cum en esis ance mechanisms by exe ing mul i- a ge in acellula s ess. Thei analysis also
highligh ed he po en ial hepa o oxici y and neph o oxici y associa ed wi h p olonged combina ion he apy,
emphasizing he need o igilan clinical moni o ing.
Sulbac am-based he apy displayed mode a e clinical e ec i eness, wi h cu e a es anging om 60–
65% and mo ali y a es o app oxima ely 32.5%. Peleg e al. (2008) p o ided an ea ly and comp ehensi e
explana ion o sulbac am’s in insic bac e icidal ac i i y agains Acine obac e baumannii, desc ibing i s
in e ac ion wi h penicillin-binding p o eins and i s he apeu ic ole beyond unc ioning solely as a β-lac amase
inhibi o . Howa d e al. (2012) u he discussed egional.di e ences in ea men ou comes d i en by di e se
gene ic esis ance de e minan s. Thei indings highligh he con inuing ele ance o sulbac am, pa icula ly in
esou ce-limi ed se ings whe e access o no el he apies may be cons ained.
Colis in mono he apy, in con as , exhibi ed limi ed e ec i eness, wi h clinical cu e a es o 50–60% and
mo ali y a es anging om 35–40%. Du an e-Mangoni e al. (2015) showed ha al hough colis in possesses
s ong memb ane- dis up i e ac i i y, i s clinical u ili y is unde mined by subs an ial neph o oxici y, which
occu ed in almos hal o he pa ien s included in hei s udy. Thei indings con inue o in o m clinical guidelines,
cau ioning clinicians ega ding he oxici y associa ed wi h colis in when used as a single agen . Ka akons an is
and Gikas (2020) also no ed he global eme gence o colis in esis ance genes, pa icula ly mc a ian s, which
u he comp omise he eliabili y o mono he apy and unde sco e he shi owa d combina ion o al e na i e
he apeu ic s a egies.
Among all e iewed egimens, igecycline demons a ed he lowes he apeu ic pe o mance, wi h a
clinical cu e a e o app oxima ely 50% and he highes mo ali y a e a 42.5%. Lin and Lan (2020) discussed
igecycline’s pha macokine ic limi a ions, including i s low se um concen a ion and insu icien bac e icidal
ac i i y, which educe i s e ec i eness in bloods eam in ec ions. Al hough igecycline e ains b oad-spec um
co e age, hese limi a ions con ibu e o i s in e io clinical pe o mance agains MDR Acine obac e baumannii
when compa ed wi h newe agen s. Wong e al. (2017) u he no ed ha while igecycline may p o ide some
bene i in espi a o y o so issue in ec ions, i should no be used as mono he apy o sys emic o li e- h ea ening
Acine obac e baumannii in ec ions, ein o cing he need o mo e po en al e na i es o combina ion egimens in
c i ically ill pa ien s.
O e all, he indings demons a e a clea in e se ela ionship be ween clinical cu e a es and mo ali y.
Regimens wi h highe cu e a es end o achie e lowe mo ali y, as obse ed wi h ce ide ocol and colis in–
i ampicin combina ion he apy. Con e sely, olde mono he apies such as igecycline and colis in alone
demons a e educed e ec i eness and highe oxici y isks. These ou comes emphasize he impo ance o
e idence-based an ibio ic selec ion and suppo he expanded use o combina ion he apies and no el agen s in
he managemen o MDR Acine obac e baumanniii in ec ions. The Wo ld Heal h O ganiza ion (2017) has
classi ied ca bapenem- esis an Acine obac e baumannii as a c i ical-p io i y pa hogen, unde sco ing he global
need o imp o ed he apeu ic s a egies, s eng hened an imic o ce ide ocol, p o ide be e e icacy and sa e y
compa ed o adi ional he apies like colis in mono he apy.
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Table 2: Summa y o Analysis o Clinical Su i al Ra es Ac oss Pa ien Subg oups Wi h MDR
Acine obac e baumannii In ec ion
Table 2 p esen s a subg oup analysis compa ing su i al ou comes be ween mono he apy and
combina ion he apy inpa ien s in ec ed wi h mul id ug- esis an Acine obac e baumannii (MDR A. baumannii),
analyzed acco ding o clinical se e i y, bac e ial esis ance ype, in ec ion si e, and obse a ion pe iod. The
indings indica e ha combina ion he apy gene ally p o ides supe io su i al ou comes ac oss mos subg oups,
pa icula ly among pa ien s wi h mode a e disease se e i y and speci ic in ec ion ypes.
Wi h espec o disease se e i y measu ed using APACHE II sco es, pa ien s wi h mode a e sco es (<20)
demons a ed signi ican ly imp o ed su i al when ea ed wi h combina ion he apy (pooled OR = 0.67; 95% CI
= [0.54, 0.85]; p = 0.0008). This ou come sugges s ha combina ion he apy is mo e ad an ageous o indi iduals
wi h less c i ical illness. In con as , among pa ien s wi h highe APACHE II sco es (>20), no signi ican
di e ence was obse ed be ween mono he apy and combina ion he apy (pooled OR = 0.99; p = 0.98). This
inding indica es ha he bene i o combina ion he apy diminishes in se e ely ill pa ien s, likely due o ex ensi e
o gan dys unc ion o inadequa e d ug pene a ion du ing c i ical in ec ions.
When s a i ied by bac e ial esis ance ype, combina ion he apy demons a ed a clea ad an age in ca bapenem-
esis an Acine obac e baumannii (CRAB) in ec ions, wi h an odds a io o 0.76 (95% CI = [0.62, 0.93]; p =
0.009). This esul highligh s he enhanced e icacy o combina ion egimens in o e coming ca bapenem
esis ance. Howe e , no s a is ically signi ican su i al ad an age was obse ed in in ec ions caused by
mul id ug- esis an (MDRAB) o ex ensi ely d ug- esis an (XDRAB) s ains (p > 0.05). In e es ingly,
mono he apy appea ed sligh ly a o ed in MDRAB cases (OR = 1.25), al hough his di e ence lacked clinical
signi icance and may e lec s udy he e ogenei y and a iabili y in d ug suscep ibili y among included ials.
Analysis o in ec ion si es e ealed ha pa ien s wi h bloods eam in ec ions bene i ed mos om
combina ion he apy, which signi ican ly educed mo ali y (OR = 0.60; 95% CI = [0.39, 0.93]; p = 0.02). In
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con as , no signi ican su i al di e ences we e obse ed in lung o mixed-si e in ec ions (p > 0.05), whe e
mono he apy and combina ion he apy p oduced compa able esul s. This end sugges s ha combina ion he apy
may con e a s onge su i al ad an age in sys emic in ec ions cha ac e ized by highe bac e ial load, whe e
syne gis ic an imic obial e ec s a e essen ial o apid bac e ial clea ance.
Rega ding obse a ion pe iod, combina ion he apy consis en ly yielded a a o able end ac oss all
assessed du a ions—14, 28, 30, and 90 days—al hough none o hese di e ences eached s a is ical signi icance
(all p > 0.05). The pe sis en p e e ence o combina ion he apy ac oss ime poin s indica es a po en ial sus ained
clinical bene i ; howe e , longe - e m ollow-up s udies a e equi ed o con i m i s du abili y in imp o ing
su i al ou comes.
O e all, he subg oup analysis suppo s he conclusion ha combina ion he apy p o ides a su i al
ad an age o e mono he apy in selec ed pa ien g oups, pa icula ly hose wi h mode a e disease se e i y,
ca bapenem- esis an in ec ions, and bloods eam in ol emen . The educed he e ogenei y (I² < 50% in mos
subg oups) enhances he eliabili y o hese indings. These esul s a e consis en wi h p e ious e idence
demons a ing he syne gis ic e ec s o combina ion egimens—such as colis in wi h i ampicin o
ca bapenems—which imp o e bac e ial clea ance and educe mo ali y compa ed wi h mono he apy (Du an e-
Mangoni e al., 2015; Ka akons an is & Gikas, 2020). Consequen ly, he analysis ein o ces he impo ance o
indi idualized, e idence-based an ibio ic selec ion and highligh s combina ion he apy as a mo e e ec i e
s a egy o imp o ing su i al ou comes in pa ien s wi h MDRAcine obac e baumannii in ec ions.
Figu e 1: Clinical cu e a es and mo ali y a es o a ious an ibio ic egimens o mul id ug- esis an
Acine obac e baumannii (2015–2025).
Figu e 1 p esen s a compa a i e analysis o clinical cu e a es and mo ali y ou comes among majo
an ibio ic egimens used o he ea men o mul id ug- esis an Acine obac e baumannii (MDR A. baumannii)
in ec ions be ween 2015 and 2025. The indings indica e ha ce ide ocol achie ed he highes he apeu ic success,
wi h clinical cu e a es eaching app oxima ely 80% and he lowes eco ded mo ali y a a ound 22.5%. This
supe io pe o mance is a ibu ed o ce ide ocol’s mechanism as a side opho e cephalospo in, which enables
bac e ial cell en y h ough i on anspo channels and allows he d ug o e ade β-lac amase–media ed
deg ada ion and e lux pump esis ance. Lin and Lan (2020) emphasized his i on-media ed en y sys em in hei
e iew o MDR Acine obac e baumannii pa hogenici y, highligh ing i s abili y o bypass classical esis ance
mechanisms and posi ioning ce ide ocol as a leading nex -gene a ion agen agains ca bapenem- esis an s ains.
Addi ional e idence om Ka akons an is and Gikas (2020) u he suppo s he supe io bac e icidal
ac i i y o ce ide ocol. Thei sys ema ic e alua ion o an imic obial s a egies demons a ed ha ce ide ocol
main ains s ong in- i o ac i i y agains isola es ha bo ing mul iple esis ance de e minan s. They also no ed i s
lowe neph o oxici y ela i e o adi ional las -line agen s such as colis in. Findings om Du an e-Mangoni e al.
(2015), al hough ocused on colis in-based egimens, p o ide essen ial his o ical con ex on he limi a ions o
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ea lie he apies and highligh he need o sa e , mo e e ec i e an imic obial op ions, he eby ein o cing he
clinical alue o newe agen s such as ce ide ocol.
The combina ion o colis in and i ampicin also showed imp o ed ou comes, achie ing cu e a es o
app oxima ely70–75% and a lowe mo ali y a e o 27.5% compa ed o colis in mono he apy. Du an e-Mangoni
e al. (2015) es ablished ounda ional e idence o his obse a ion, demons a ing he syne gis ic e ec o colis in
and i ampicin h ough enhanced memb ane pene a ion and inhibi ion o RNA syn hesis. Al hough he s udy
p eda es widesp ead use o ce ide ocol, i emains a pi o al e e ence de ailing bo h he bene i s and limi a ions
o combina ion he apy du ing ea lie phases o escala ing an imic obial esis ance. Ka akons an is and Gikas
(2020) u he elabo a ed on i ampicin’s capaci y o coun e esis ance when pai ed wi h colis in by exe ing
mul i- a ge s ess on bac e ial cells, while also emphasizing he need o close moni o ing due o po en ial hepa ic
and enal oxici y.
Sulbac am-based he apy demons a ed mode a e clinical e ec i eness, wi h cu e a es anging om 60–
65% and mo ali y a es o app oxima ely 32.5%. Peleg e al. (2008) we e among he i s o desc ibe sulbac am’s
in insic bac e icidal p ope ies agains Acine obac e baumannii, explaining i s in e ac ion wi h penicillin-binding
p o eins and i s he apeu ic ole beyond unc ioning solely as a β-lac amase inhibi o . Howa d e al. (2012)
expanded on his by documen ing global a ia ions in ea men e ec i eness a ising om di e se gene ic
esis ance pa e ns, unde sco ing sulbac am’s con inued ele ance— pa icula ly in esou ce-limi ed heal hca e
se ings.
Colis in mono he apy demons a ed limi ed e ec i eness, wi h cu e a es o 50–60% and mo ali y a es
o 35–40%. Du an e-Mangoni e al. (2015) showed ha despi e i s s ong memb ane-dis up ing p ope ies, colis in
is signi ican ly unde mined by neph o oxici y, which a ec ed nea ly hal o he pa ien s in hei ial. Thei
indings con inue o in o m clinical guidelines cau ioning agains he ou ine use o colis in as a s andalone agen .
Ka akons an is and Gikas (2020) addi ionally highligh ed he global ise o mc -media ed colis in esis ance,
u he educing he eliabili y o mono he apy and suppo ing he shi owa d combina ion o al e na i e
ea men s.
Among he e iewed egimens, igecycline exhibi ed he lowes he apeu ic pe o mance, wi h clinical
cu e a es o app oxima ely 50% and he highes mo ali y a e a 42.5%. Lin and Lan (2020) a ibu ed his
ou come o igecycline’s pha macokine ic limi a ions, pa icula ly i s low se um concen a ions and insu icien
bac e icidal ac i i y, which es ic i s e ec i eness in bloods eam in ec ions. Wong e al. (2017) also no ed ha
al hough igecycline may be bene icial o ce ain espi a o y o so - issue in ec ions, i is unsui able as
mono he apy o se e e sys emic Acine obac e baumannii in ec ions, emphasizing he need o mo e po en
al e na i es in c i ically ill pa ien s.
O e all, he esul s show a clea in e se ela ionship be ween clinical cu e a es and mo ali y ou comes:
egimens wi h highe cu e a es co espond o lowe mo ali y. Ce ide ocol and colis in– i ampicin combina ion
he apy o e he mos a o able balance o e icacy and sa e y, whe eas olde mono he apies—including
igecycline and colis in—demons a e lowe e ec i eness and highe oxici y isks. These indings highligh he
impo ance o e idence-based an ibio ic selec ion and suppo he adop ion o combina ion egimens and no el
an imic obial agen s in he managemen o MDR Acine obac e baumannii in ec ions. The Wo ld Heal h
O ganiza ion (2017) has designa ed ca bapenem- esis an Acine obac e baumannii as a c i ical-p io i y pa hogen,
unde sco ing he u gen global need o imp o ed he apeu ic s a egies, s eng hened an imic obial s ewa dship,
and con inued in es men in esea ch o add ess ising mul id ug esis an .
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Figu e 2: Compa ison o 28-Day Mo ali y Among An ibio ic Regimens
Figu e 2 p esen s e idence om mul iple s udies, including he in es iga ion conduc ed by Deng e al.
(2022), which highligh s se e al consis en hemes ega ding p edic o s o mo ali y and e ec i e he apeu ic
s a egies o mul id ug- esis an Acine obac e baumannii (MDR-AB) and ca bapenem- esis an A. baumannii
(CRAB) pneumonia. Ac oss he li e a u e, pa ien - ela ed ac o s—such as ad anced age—and se e i y-o - illness
indica o s, including in asi e ca he e iza ion and mechanical en ila ion, consis en ly eme ge as signi ican
de e minan s o clinical ou comes. In he e e enced s udy, pa ien s olde han 75 yea s demons a ed ma kedly
highe mo ali y, suppo ing p e ious indings ha immunosenescence, mul iple como bidi ies, and gene al
physiologic decline subs an ially inc ease he isk o dea h in se e e MDR-AB in ec ions. The pe sis en
associa ion be ween in asi e p ocedu es and inc eased mo ali y u he sugges s ha de ice- ela ed
complica ions and p olonged in ensi e ca e may nega i ely in luence p ognosis.
F om a he apeu ic pe spec i e, he e idence ein o ces he ad an ages o combina ion an ibio ic
egimens, pa icula ly hose inco po a ing igecycline o sulbac am, in imp o ing su i al among pa ien s wi h
CRAB pneumonia. Ac oss obse a ional coho s and clinical s udies, igecycline-con aining combina ions ha e
been associa ed wi h a o able ou comes when minimum inhibi o y concen a ion (MIC) alues a e wi hin
e ec i e anges and when ea men is ini ia ed p omp ly. The obse a ion ha igecycline-based egimens
signi ican ly educed mo ali y co esponds wi h ea lie pha macodynamic da a demons a ing igecycline’s
sus ained in- i o ac i i y agains MDR-AB in ce ain geog aphic egions.
Simila ly, sulbac am con inues o be emphasized in he li e a u e due o i s in insic an imic obial ac i i y
agains Acine obac e species. The inding ha sulbac am-con aining combina ion egimens educed mo ali y is
consis en wi h exis ing epo s indica ing ha sulbac am—pa icula ly when adminis e ed a highe doses—may
exe syne gis ic e ec s alongside ca bapenems. Al hough he s udy did no iden i y a s a is ically signi ican
di e ence be ween high-dose (>3 g/day) and low-dose (≤3 g/day) sulbac am, he end owa ds imp o ed
ou comes a highe doses mi o s pha macokine ic and pha macodynamic analyses, which sugges ha inc eased
sulbac am exposu e may be necessa y o achie e he apeu ic a ge s in se e e CRAB in ec ions.
Despi e hese encou aging indings, cau ion is wa an ed when in e p e ing he a ailable e idence. Many
s udies, including ha o Deng e al., a e limi ed by e ospec i e designs, he e ogeneous ea men egimens, and
small subg oup popula ions, which es ic he accu acy o dose– esponse assessmen s. Mo eo e , impo an
mic obiological ac o s—such as esis ance de e minan s, syne gy es ing, and se um d ug concen a ion
moni o ing—a e o en no e alua ed, limi ing insigh in o he mechanis ic basis o obse ed clinical
imp o emen s.
O e all, he syn hesized e idence indica es ha ea ly ini ia ion o e ec i e combina ion he apy plays a
c i ical ole in imp o ing ou comes among pa ien s wi h CRAB pneumonia, while ad anced age and ma ke s o
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se e e illness consis en ly p edic poo e p ognosis. The indings highligh he need o u u e esea ch o ocus
on andomized con olled ials, s anda dized sulbac am dosing s a egies, and mechanis ic in es iga ions
e alua ing an imic obial syne gy and pha macodynamic beha io . Such e o s a e essen ial o e ining
he apeu ic p o ocols and enhancing clinical ou comes in his inc easingly challenging in ec ion.
ACKNOWLEDGEMENT
The au ho s wish o exp ess hei u mos g a i ude o Almigh y God o His di ine guidance, g ace, and
s eng h, which sus ained and inspi ed hem h oughou he comple ion o his sys ema ic e iew, and o P o .
Gecelene Es o ico o he in aluable men o ship, insigh ul eedback, and s ead as suppo , which g ea ly
enhanced he igo and cla i y o his wo k.
CONCLUSION
This sys ema ic e iew demons a es ha he e ec i e managemen o mul id ug- esis an Acine obac e
baumannii (MDR A. baumannii) elies hea ily on he s a egic selec ion o an ibio ic egimens, wi h combina ion
he apies and no el an imic obial agen s consis en ly ou pe o ming adi ional mono he apies. Ac oss he
e idence examined, colis in and igecycline mono he apies showed only mode a e clinical bene i and we e
equen ly associa ed wi h conside able oxici y, ein o cing hei limi a ions as s and-alone ea men s in se e e
MDR in ec ions. In con as , combina ion egimens—pa icula ly colis in pai ed wi h i ampicin o
ca bapenems—p o ided signi ican ly highe clinical cu e a es and lowe mo ali y, unde sco ing he syne gis ic
ad an age o mul i-d ug s a egies in o e coming complex esis ance mechanisms.
The mos no able ad ancemen highligh ed in his e iew is he eme gence o ce ide ocol, a side opho e
cephalospo in ha demons a ed he highes he apeu ic success, wi h cu e a es eaching 70–80% and he lowes
epo ed mo ali y (20–25%). I s abili y o bypass β-lac amase–media ed esis ance and main ain obus ac i i y
agains ca bapenem- esis an s ains posi ions i as a leading he apeu ic op ion o MDR A. baumannii.
Sulbac am-based he apies also showed consis en mode a e e icacy, making hem a aluable op ion in esou ce-
limi ed se ings whe e no el agen s may be inaccessible.
Subg oup analyses u he emphasize ha combina ion he apy o e s clea su i al bene i s among
pa ien s wi h mode a e illness se e i y, bloods eam in ec ions, and ca bapenem- esis an s ains. Howe e , i s
ad an ages diminish in c i ically ill pa ien s wi h high APACHE II sco es, sugges ing ha disease se e i y and
hos ac o s emain key de e minan s o he apeu ic esponse.
O e all, he indings clea ly suppo a shi owa d e idence-based, indi idualized an ibio ic selec ion
ha p io i izes no el agen s and combina ion egimens o e adi ional mono he apy. S eng hened an imic obial
s ewa dship, con inuous su eillance o eme ging esis ance pa e ns, and u he high-quali y andomized
con olled ials a e essen ial o op imize ea men ou comes and cu b he g owing global h ea posed by MDR
A. baumannii.
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