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Emergence of ST119 Acinetobacter pittii co-harbouring NDM-1 and OXA-58 in Malaysia

Ang GY, Yu CY, Cheong YM, Yin WF, Chan KG

Int J Antimicrob Agents, 2016 Feb;47(2):168-9.
PMID: 26742728 DOI: 10.1016/j.ijantimicag.2015.11.008
Matched MeSH terms: Acinetobacter Infections/microbiology*
Fulltext Extremely high prevalence of antiseptic resistant Quaternary Ammonium Compound E gene among clinical isolates of multiple drug resistant Acinetobacter baumannii in Malaysia

Babaei M, Sulong A, Hamat R, Nordin S, Neela V

Ann Clin Microbiol Antimicrob, 2015;14:11.
PMID: 25858356 DOI: 10.1186/s12941-015-0071-7

Antiseptics are commonly used for the management of MDR (multiple drug resistance) pathogens in hospitals. They play crucial roles in the infection control practices. Antiseptics are often used for skin antisepsis, gauze dressing, preparation of anatomical sites for surgical procedure, hand sterilization before in contact with an infected person, before an invasive procedure and as surgical scrub.

Matched MeSH terms: Acinetobacter Infections/microbiology*
Molecular characterization of carbapenemase and cephalosporinase genes among clinical isolates of Acinetobacter baumannii in a tertiary medical centre in Malaysia

Biglari S, Alfizah H, Ramliza R, Rahman MM

J Med Microbiol, 2015 Jan;64(Pt 1):53-8.
PMID: 25381148 DOI: 10.1099/jmm.0.082263-0

Antimicrobial resistance in Acinetobacter baumannii is a growing public health concern and an important pathogen in nosocomial infections. We investigated the genes involved in resistance to carbapenems and cephalosporins in clinical A. baumannii isolates from a tertiary medical centre in Malaysia. A. baumannii was isolated from 167 clinical specimens and identified by sequencing of the 16S rRNA and rpoB genes. The MIC for imipenem, meropenem, ceftazidime and cefepime were determined by the E-test method. The presence of carbapenemase and cephalosporinase genes was investigated by PCR. The isolates were predominantly nonsusceptible to carbapenems and cephalosporins (>70 %) with high MIC values. ISAba1 was detected in all carbapenem-nonsusceptible A. baumannii harbouring the blaOXA-23-like gene. The presence of blaOXA-51-like and ISAba1 upstream of blaOXA-51 was not associated with nonsusceptibility to carbapenems. A. baumannii isolates harbouring ISAba1-blaADC (85.8 %) were significantly associated with nonsusceptibility to cephalosporins (P<0.0001). However, ISAba1-blaADC was not detected in a minority (<10 %) of the isolates which were nonsusceptible to cephalosporins. The acquired OXA-23 enzymes were responsible for nonsusceptibility to carbapenems in our clinical A. baumannii isolates and warrant continuous surveillance to prevent further dissemination of this antibiotic resistance gene. The presence of ISAba1 upstream of the blaADC was a determinant for cephalosporin resistance. However, the absence of this ISAba1-blaADC in some of the isolates may suggest other resistance mechanisms and need further investigation.

Matched MeSH terms: Acinetobacter Infections/microbiology*
Antimicrobial Resistance Mechanisms and Genetic Diversity of Multidrug-Resistant Acinetobacter baumannii Isolated from a Teaching Hospital in Malaysia

Biglari S, Hanafiah A, Mohd Puzi S, Ramli R, Rahman M, Lopes BS

Microb Drug Resist, 2017 Jul;23(5):545-555.
PMID: 27854165 DOI: 10.1089/mdr.2016.0130

Multidrug-resistant (MDR) Acinetobacter baumannii has increasingly emerged as an important nosocomial pathogen. The aim of this study was to determine the resistance profiles and genetic diversity in A. baumannii clinical isolates in a tertiary medical center in Malaysia. The minimum inhibitory concentrations of carbapenems (imipenem and meropenem), cephalosporins (ceftazidime and cefepime), and ciprofloxacin were determined by E-test. PCR and sequencing were carried out for the detection of antibiotic resistance genes and mutations. Clonal relatedness among A. baumannii isolates was determined by REP-PCR. Sequence-based typing of OXA-51 and multilocus sequence typing were performed. One hundred twenty-five of 162 (77.2%) A. baumannii isolates had MDR phenotype. From the 162 A. baumannii isolates, 20 strain types were identified and majority of A. baumannii isolates (66%, n = 107) were classified as strain type 1 and were positive for ISAba1-blaOXA-23and ISAba1-blaADCand had mutations in both gyrA and parC genes at positions, 83 and 80, resulting in serine-to-leucine conversion. REP-PCR analysis showed 129 REP types that generated 31 clones with a 90% similarity cutoff value. OXA-66 variant of the blaOXA-51-likegenes was predominantly detected among our A. baumannii clinical isolates belonging to ST195 (found in six clones: 1, 8, 9, 19, 27, and 30) and ST208 (found in clone 21). The study helps us in understanding the genetic diversity of A. baumannii isolates in our setting and confirms that international clone II is the most widely distributed clone in Universiti Kebangsaan Malaysia Medical Centre, Malaysia.

Matched MeSH terms: Acinetobacter Infections/microbiology
Fulltext Risk factors and outcomes of imipenem-resistant Acinetobacter bloodstream infection in North-Eastern Malaysia

Deris ZZ, Shafei MN, Harun A

Asian Pac J Trop Biomed, 2011 Aug;1(4):313-5.
PMID: 23569782 DOI: 10.1016/S2221-1691(11)60050-6

To determine the risk factors and outcomes of imipenem-resistant Acinetobacter baumannii (IRAB) bloodstream infection (BSI) cases, since there is very little publication on Acinetobacter baumannii infections from Malaysia.

Matched MeSH terms: Acinetobacter Infections/microbiology
Outcomes and appropriateness of management of nosocomial Acinetobacter bloodstream infections at a teaching hospital in northeastern Malaysia

Deris ZZ, Harun A, Shafei MN, Rahman RA, Johari MR

Southeast Asian J. Trop. Med. Public Health, 2009 Jan;40(1):140-7.
PMID: 19323046

Acinetobacter spp is a known nosocomial pathogen causing a wide range of clinical diseases such as pneumonia, wound infection and bloodstream infections (BSI). The clinical outcomes of acinetobacter BSI were determined by a 1:1 case control study involving 58 confirmed cases of acinetobacter BSI who were compared to other gram-negative infections. The crude mortality of acinetobacter BSI was 47.2%, which was significantly greater than other gram-negative BSI (OR 1.89, 95% CI 1.10-3.24) but there were no significant differences in attributed mortality between the two groups. We found that patients treated in intensive care units (ICU), who had longer ICU stays, who presented with shock or coagulopathy, had prior exposure to carbapenems, had mechanical ventilation, were on a ventilator for longer periods, had a nasogastric tube, had an arterial catheter or had parenteral nutrition at a significantly greater risk of mortality due to acinetobacter BSI. Patients presenting with septic shock (OR 17.95, 95% CI 3.36-95.84) or having a central venous catheter (OR 12.48, 95% CI 1.09-142.68) were independently at higher risk for mortality. Appropriateness of therapy reduced the mortality attributes of acinetobacter BSI (OR 0.197, 95% CI 0.040-0.967) but did not significantly reduce crude mortality in acinetobacter BSI patients. This study shows the importance of preventing acinetobacter BSI and the appropriate use of antimicrobial agents to reduce mortality.

Matched MeSH terms: Acinetobacter Infections/microbiology
Fulltext The prevalence and risk factors of nosocomial Acinetobacter blood stream infections in tertiary teaching hospital in north-eastern Malaysia

Deris ZZ, Harun A, Omar M, Johari MR

Trop Biomed, 2009 Aug;26(2):123-9, 219-22.
PMID: 19901898

Acinetobacter spp. is a known nosocomial pathogen causing a wide range of clinical diseases mainly pneumonia, wound infections and blood stream infections (BSI). A cross sectional descriptive study was performed to determine the prevalence of Acinetobacter infection in Hospital Universiti Sains Malaysia, Kelantan (HUSM). The risk factors of Acinetobacter BSI were determined by 1:1 case control analytical study, involving fifty-eight confirmed cases of Acinetobacter BSI patients compared to the cases caused by Gram-negative bacteria. The prevalence of Acinetobacter BSI in the HUSM was 6.11% (95% CI 4.88-7.53%). The attack rate of Acinetobacter BSI was 2.77 episodes per 1000 hospital admissions. Acinetobacter BSI patients were mostly located in intensive care unit and had a longer intensive care unit stay. In univariate analysis, the risk factors for Acinetobacter BSI include prior exposure to antimicrobial agents such as penicillins, aminoglycosides and cephalosporins, mechanical ventilation, presence of nasogastric tube, arterial catheter and urinary catheter. In multivariate analysis, the independent risk factors for Acinetobacter BSI were prior treatment with cephalosporins (OR 3.836 95% CI 1.657-8.881 p=0.002) and mechanical ventilation (OR 3.164 95% CI 1.353-7.397 p=0.008). This study revealed that rational use of antimicrobial agents is of paramount importance to control Acinetobacter BSI.

Matched MeSH terms: Acinetobacter Infections/microbiology
In vitro activity of tigecycline against Acinetobacter baumannii isolates from a teaching hospital in Malaysia

Dhabaan GN, AbuBakar S, Shorman MA, Hassan H

J Chemother, 2012 Apr;24(2):87-92.
PMID: 22546763 DOI: 10.1179/1120009X12Z.00000000017

The In vitro susceptibility of clinical and environmental isolates of Acinetobacter baumannii to tigecycline and other antibiotics was determined by disk diffusion method. The E-test was used to determine the minimum inhibitory concentration (MIC). The growth curves of tigecycline treated environmental and clinical strains were established. Fifty-seven percent and 75% of the clinical and environmental isolates were MDR strains, respectively. Ninety-five percent of the clinical isolates were susceptible to tigecycline and 5% showed intermediate resistance with MIC ranging between 0.032 and 3 mg/l. Tigecycline susceptible and intermediate resistance among the environmental isolates were 40% and 60%, respectively, with a significantly lower MIC range of 0.5-4 mg/l. The bacterial growth curves demonstrated the higher ability of the environmental strains to tolerate the antibiotic effects than the clinical strains. The relatively high resistance profile among the environmental isolate suggests an insidious emergence of tigecycline resistance amongst A. baumannii. Strict infection control procedures are imperative to prevent the dissemination of tigecycline-resistant A. baumannii strains in the hospital environment.

Matched MeSH terms: Acinetobacter Infections/microbiology
Fulltext Genome sequence of Acinetobacter baumannii AC12, a polymyxin-resistant strain isolated from Terengganu, Malaysia

Gan HM, Lean SS, Suhaili Z, Thong KL, Yeo CC

J Bacteriol, 2012 Nov;194(21):5979-80.
PMID: 23045494 DOI: 10.1128/JB.01466-12

Acinetobacter baumannii is a major cause of nosocomial infection worldwide. We report the draft genome sequence of A. baumannii AC12, a multidrug-resistant nosocomial strain with additional resistance to carbapenems and polymyxin. The genome data will provide insights into the genetic basis of antimicrobial resistance and its adaptive mechanism.

Matched MeSH terms: Acinetobacter Infections/microbiology
Demonstration of an outer membrane protein that is antigenically specific for Acinetobacter baumannii

Islam AH, Singh KK, Ismail A

Diagn Microbiol Infect Dis, 2011 Jan;69(1):38-44.
PMID: 21146712 DOI: 10.1016/j.diagmicrobio.2010.09.008

Acinetobacter baumannii is an emerging nosocomial pathogen that is resistant to many types of antibiotics, and hence, a fast, sensitive, specific, and economical test for its rapid diagnosis is needed. Development of such a test requires a specific antigen, and outer membrane proteins (OMPs) are the prime candidates. The goal of this study was to find a specific OMP of A. baumannii and demonstrate the presence of specific IgM, IgA, and IgG against the candidate protein in human serum. OMPs of A. baumannii ATCC 19606 and 16 other clinical isolates of A. baumannii were extracted from an overnight culture grown at 37 °C. Protein profiles were obtained using sodium dodecyl sulfate polyacrylamide gel electrophoresis, and Western blot analysis was performed to detect the presence of IgM, IgA, and IgG against the OMP in host serum. An antigenic 34.4-kDa OMP was uniquely recognized by IgM, IgA, and IgG from patients with A. baumannii infection, and it did not cross-react with sera from patients with other types of infection. The band was also found in the other 16 A. baumannii isolates. This 34.4-kDa OMP is a prime candidate for development of a diagnostic test for the presence of A. baumannii.

Matched MeSH terms: Acinetobacter Infections/microbiology
Comparative efficacy and safety of treatment options for MDR and XDR Acinetobacter baumannii infections: a systematic review and network meta-analysis

Kengkla K, Kongpakwattana K, Saokaew S, Apisarnthanarak A, Chaiyakunapruk N

J Antimicrob Chemother, 2018 Jan 01;73(1):22-32.
PMID: 29069421 DOI: 10.1093/jac/dkx368

Objectives: To comprehensively compare and rank the efficacy and safety of available treatment options for patients with MDR and XDR Acinetobacter baumannii (AB) infection.
Methods: We searched PubMed, Embase and the Cochrane register of trials systematically for studies that examined treatment options for patients with MDR- and XDR-AB infections until April 2016. Network meta-analysis (NMA) was performed to estimate the risk ratio (RR) and 95% CI from both direct and indirect evidence. Primary outcomes were clinical cure and microbiological cure. Secondary outcomes were all-cause mortality and nephrotoxic and non-nephrotoxic adverse events.
Results: A total of 29 studies with 2529 patients (median age 60 years; 65% male; median APACHE II score 19.0) were included. Although there were no statistically significant differences between treatment options, triple therapy with colistin, sulbactam and tigecycline had the highest clinical cure rate. Colistin in combination with sulbactam was associated with a significantly higher microbiological cure rate compared with colistin in combination with tigecycline (RR 1.23; 95% CI 1.03-1.47) and colistin monotherapy (RR 1.21; 95% CI 1.06-1.38). No significant differences in all-cause mortality were noted between treatment options. Tigecycline-based therapy also appeared less effective for achieving a microbiological cure and is not appropriate for treating bloodstream MDR- and XDR-AB infections.
Conclusions: Combination therapy of colistin with sulbactam demonstrates superiority in terms of microbiological cure with a safety profile similar to that of colistin monotherapy. Thus, our findings support the use of this combination as a treatment for MDR- and XDR-AB infections.

Matched MeSH terms: Acinetobacter Infections/microbiology
Fulltext Spread of carbapenem-resistant Acinetobacter baumannii global clone 2 in Asia and AbaR-type resistance islands

Kim DH, Choi JY, Kim HW, Kim SH, Chung DR, Peck KR, et al.

Antimicrob Agents Chemother, 2013 Nov;57(11):5239-46.
PMID: 23939892 DOI: 10.1128/AAC.00633-13

In this surveillance study, we identified the genotypes, carbapenem resistance determinants, and structural variations of AbaR-type resistance islands among carbapenem-resistant Acinetobacter baumannii (CRAB) isolates from nine Asian locales. Clonal complex 92 (CC92), corresponding to global clone 2 (GC2), was the most prevalent in most Asian locales (83/108 isolates; 76.9%). CC108, or GC1, was a predominant clone in India. OXA-23 oxacillinase was detected in CRAB isolates from most Asian locales except Taiwan. blaOXA-24 was found in CRAB isolates from Taiwan. AbaR4-type resistance islands, which were divided into six subtypes, were identified in most CRAB isolates investigated. Five isolates from India, Malaysia, Singapore, and Hong Kong contained AbaR3-type resistance islands. Of these, three isolates harbored both AbaR3- and AbaR4-type resistance islands simultaneously. In this study, GC2 was revealed as a prevalent clone in most Asian locales, with the AbaR4-type resistance island predominant, with diverse variants. The significance of this study lies in identifying the spread of global clones of carbapenem-resistant A. baumannii in Asia.

Matched MeSH terms: Acinetobacter Infections/microbiology
Antimicrobial susceptibility profiling and genomic diversity of multidrug-resistant Acinetobacter baumannii isolates from a teaching hospital in Malaysia

Kong BH, Hanifah YA, Yusof MY, Thong KL

Jpn J Infect Dis, 2011;64(4):337-40.
PMID: 21788713

The resistance phenotypes and genomic diversity of 185 Acinetobacter baumannii isolates obtained from the intensive care unit (ICU) of a local teaching hospital in Kuala Lumpur from 2006 to 2009 were determined using antimicrobial susceptibility testing and pulsed-field gel electrophoresis (PFGE). Antibiogram analyses showed that the isolates were fully resistant to β-lactam antimicrobials and had high resistance rates to the other antimicrobial agents tested. However, the isolates were susceptible to polymyxin B. Resistance to cefoperazone/sulbactam was only detected in strains isolated from 2007 to 2009. Some environmental isolates and an isolate from the hands of a healthcare worker (HCW) had identical resistance profiles and PFGE profiles that were closely related to patient isolates. Cluster analyses based on the PFGE profiles showed there was a persistent clone of endemic isolates in the ICU environment. The transmission route from HCWs to fomites to patients, which caused a long-term infection in the ICU of the University Malaya Medical Centre, was observed in this study. These data provide a better understanding of A. baumannii epidemiology within the hospital and the possible transmission routes. Knowledge of changes in the resistance rates of A. baumannii in our local hospital will improve antimicrobial therapy.

Matched MeSH terms: Acinetobacter Infections/microbiology
Acinetobacter baumannii respiratory isolates in ventilated patients are associated with prolonged hospital stay

Loh LC, Yii CT, Lai KK, Seevaunnamtum SP, Pushparasah G, Tong JM

Clin Microbiol Infect, 2006 Jun;12(6):597-8.
PMID: 16700715
Matched MeSH terms: Acinetobacter Infections/microbiology*
Acinetobacter endocarditis in children: a case report and review of the literature

Malik AS

Infection, 1995 9 1;23(5):306-8.
PMID: 8557392

Acinetobacter calcoaceticus, a gram-negative bacterium ubiquitous in soil, water and sewage, is a rare cause of endocarditis in children. The first case of Acinetobacter endocarditis in an infant is described. This patient had underlying tetralogy of Fallot with absent pulmonary valve. A review of the literature in English revealed only four other cases of Acinetobacter endocarditis in children; three of whom had underlying congenital heart disease. Like the other reported cases, this patient responded well to antibiotic treatment. Subsequently this patient underwent corrective cardiac surgery but died of post-operative complications.

Matched MeSH terms: Acinetobacter Infections/microbiology
An overview of Acinetobacter baumannii pathogenesis: Motility, adherence and biofilm formation

Mea HJ, Yong PVC, Wong EH

Microbiol Res, 2021 Jun;247:126722.
PMID: 33618061 DOI: 10.1016/j.micres.2021.126722

The Gram-negative opportunistic pathogen Acinetobacter baumannii has gain notoriety in recent decades, primarily due to its propensity to cause nosocomial infections in critically ill patients. Its global spread, multi-drug resistance features and plethora of virulence factors make it a serious threat to public health worldwide. Though much effort has been expended in uncovering its successes, it continues to confound researchers due to its highly adaptive nature, mutating to meet the needs of a given environment. Its persistence in the clinical setting allows it to be in close proximity to a potential host, where contact can be made facilitating infection and colonization. In this article, we aim to provide a current overview of the bacterial virulence factors, specifically focusing on factors involved in the initial stages of infection, highlighting the role of adaptation facilitated by two-component systems and biofilm formation. Finally, the study of host-pathogen interactions using available animal models, their suitability, notable findings and some perspectives moving forward are also discussed.

Matched MeSH terms: Acinetobacter Infections/microbiology*
Antibiotic susceptibility and REP-PCR fingerprints of Acinetobacter spp. isolated from a hospital ten years apart

Misbah S, AbuBakar S, Hassan H, Hanifah YA, Yusof MY

J Hosp Infect, 2004 Dec;58(4):254-61.
PMID: 15564001

The antibiotic susceptibility profiles and the repetitive extragenic palindromic sequence-based polymerase chain reaction (REP-PCR)-determined genotypes of 109 Acinetobacter strains collected from the University Malaya Medical Center (UMMC), Kuala Lumpur, Malaysia, in 1987 (N=21) and 1996-1998 (N=88) were established. Twelve antibiotic susceptibility profiles of antibiotics used at the UMMC were obtained. In descending order of effectiveness, imipenem, amikacin and ciprofloxacin were the most effective against the Acinetobacter strains. Compared with 1987 isolates, the isolates obtained in 1996-1998 had decreased susceptibility to these antibiotics and were tolerant to the antibiotics up to an MIC90 of > or =256 mg/L. REP-PCR DNA fingerprints of all the isolates revealed the presence of four Acinetobacter spp. lineages; 92% of all the isolates belonged to two dominant lineages (genotypes 1 and 4). Genotype 4 isolates predominant in 1987 showed increased resistance and antibiotic tolerance to imipenem, amikacin and ciprofloxacin compared with the 1996-1998 isolates. In contrast, genotype 1 isolates from 1996-1998 were mainly sensitive to these antibiotics. These findings demonstrate the presence of at least two independent Acinetobacter spp. lineages in the same hospital, and suggest the possibility that genotype 4 Acinetobacter spp. acquired the resistance phenotype in situ, whereas most of the genotype 1 isolates were probably introduced to the hospital in recent years.

Matched MeSH terms: Acinetobacter Infections/microbiology*
Prevalence and antimicrobial susceptibilities of Acinetobacter baumannii and non-baumannii Acinetobacters from Terengganu, Malaysia and their carriage of carbapenemase genes

Mohd Rani F, A Rahman NI, Ismail S, Abdullah FH, Othman N, Alattraqchi AG, et al.

J Med Microbiol, 2018 Nov;67(11):1538-1543.
PMID: 30251951 DOI: 10.1099/jmm.0.000844

A total of 153 non-repeat Acinetobacter spp. clinical isolates obtained in 2015 from Hospital Sultanah Nur Zahirah (HSNZ) in Terengganu, Malaysia, were characterized. Identification of the isolates at species level was performed by ribosomal DNA restriction analysis (ARDRA) followed by sequencing of the rpoB gene. The majority of the isolates (n=128; 83.7 %) were A. baumannii while the rest were identified as A. nosocomialis (n=16), A. calcoaceticus (n=5), A. soli (n=2), A. berezeniae (n=1) and A. variabilis (n=1). Multidrug resistance (MDR) was most prevalent in A. baumannnii (66.4 %) whereas only one non-baumannii isolate (A. nosocomialis) was MDR. The blaOXA-23 gene was the predominant acquired carbapenemase gene (56.2 %) and was significantly associated (P<0.001) with carbapenem resistance. However, no significant association was found for carbapenem resistance and isolates that contained the ISAba1-blaOXA-51 configuration.

Matched MeSH terms: Acinetobacter Infections/microbiology
The global prevalence of multidrug-resistance among Acinetobacter baumannii causing hospital-acquired and ventilator-associated pneumonia and its associated mortality: A systematic review and meta-analysis

Mohd Sazlly Lim S, Zainal Abidin A, Liew SM, Roberts JA, Sime FB

J Infect, 2019 12;79(6):593-600.
PMID: 31580871 DOI: 10.1016/j.jinf.2019.09.012

OBJECTIVE: The objective of this works was to assess the global prevalence of multidrug-resistance among A. baumannii causing hospital-acquired (HAP) and ventilator-associated pneumonia (VAP), and describe its associated mortality.
METHODS: We performed a systematic search of four databases for relevant studies. Meta-analysis was done based on United Nations geoscheme regions, individual countries and study period. We used a random-effects model to calculate pooled prevalence and mortality estimates with 95% confidence intervals (CIs), weighted by study size.
RESULTS: Among 6445 reports screened, we identified 126 relevant studies, comprising data from 29 countries. The overall prevalence of multidrug-resistance among A. baumannii causing HAP and VAP pooled from 114 studies was 79.9% (95% CI 73.9-85.4%). Central America (100%) and Latin America and the Caribbean (100%) had the highest prevalence, whereas Eastern Asia had the lowest (64.6%; 95% CI, 50.2-77.6%). The overall mortality estimate pooled from 27 studies was 42.6% (95% CI, 37.2-48.1%).
CONCLUSIONS: We observed large amounts of variation in the prevalence of multidrug-resistance among A. baumannii causing HAP and VAP and its mortality rate among regions and lack of data from many countries. Data from this review can be used in the development of customized strategies for infection control and antimicrobial stewardship.

Matched MeSH terms: Acinetobacter Infections/microbiology*
Semi-mechanistic PK/PD modelling of meropenem and sulbactam combination against carbapenem-resistant strains of Acinetobacter baumannii

Mohd Sazlly Lim S, Heffernan AJ, Zowawi HM, Roberts JA, Sime FB

Eur J Clin Microbiol Infect Dis, 2021 Sep;40(9):1943-1952.
PMID: 33884516 DOI: 10.1007/s10096-021-04252-z

Due to limited treatment options for carbapenem-resistant Acinetobacter baumannii (CR-AB) infections, antibiotic combinations are commonly used. In this study, we explored the potential efficacy of meropenem-sulbactam combination (MEM/SUL) against CR-AB. The checkerboard method was used to screen for synergistic activity of MEM/SUL against 50 clinical CR-AB isolates. Subsequently, time-kill studies against two CR-AB isolates were performed. Time-kill data were described using a semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model. Subsequently, Monte Carlo simulations were performed to estimate the probability of 2-log kill, 1-log kill or stasis at 24-h following combination therapy. The MEM/SUL demonstrated synergy against 28/50 isolates. No antagonism was observed. The MIC50 and MIC90 of MEM/SUL were decreased fourfold, compared to the monotherapy MIC. In the time-kill studies, the combination displayed synergistic killing against both isolates at the highest clinically achievable concentrations. At concentrations equal to the fractional inhibitory concentration, synergism was observed against one isolate. The PK/PD model adequately delineated the data and the interaction between meropenem and sulbactam. The effect of the combination was driven by sulbactam, with meropenem acting as a potentiator. The simulations of various dosing regimens revealed no activity for the monotherapies. At best, the MEM/SUL regimen of 2 g/4 g every 8 h demonstrated a probability of target attainment of 2-log10 kill at 24 h of 34%. The reduction in the MIC values and the achievement of a moderate PTA of a 2-log10 reduction in bacterial burden demonstrated that MEM/SUL may potentially be effective against some CR-AB infections.

Matched MeSH terms: Acinetobacter Infections/microbiology

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