ResearchArticle Acinetobacter baumannii Infection in...

6
Research Article Acinetobacter baumannii Infection in Transfusion Dependent Thalassemia Patients with Sepsis Muzaheed Abdul Rasheed, Faisal Mousa Alzahrani, and Saeed Sattar Shaikh Department of Clinical Laboratory Science, College of Applied Medical Sciences, University of Dammam, Dammam, Saudi Arabia Correspondence should be addressed to Muzaheed Abdul Rasheed; [email protected] Received 9 February 2017; Revised 27 April 2017; Accepted 30 April 2017; Published 17 May 2017 Academic Editor: Paola Di Carlo Copyright © 2017 Muzaheed Abdul Rasheed et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Purpose. To identify the Acinetobacter baumannii infection among transfusion dependent thalassemia patients. Methods.A quantitative approach was employed to assess Acinetobacter baumannii infection in transfusion dependent thalassemia patients. Samples were collected from 916 patients, which have shown bacterial growth on MacConkey and blood agar culture media. A. baumannii strains were identified by microbiological methods and Gram’s staining. API 20 E kit (Biomerieux, USA) was used for final identification. Results. From 916 cultured blood specimens, 107 (11.6%) showed growth of A. baumannii. Serum ferritin in thalassemic patients without bacterial infections was 3849.5 ± 1513.5 g/L versus 6413.5 ± 2103.9 g/L in those with bacterial infections ( = 0.0001). Acinetobacter baumannii infected patients have shown higher serum ferritin levels ( = 0.0001). Serum ferritin in thalassemic patients was 3849.5 ± 1513.5 g/L versus 6413.5 ± 2103.9 g/L in those with bacterial infections ( = 0.0001). Acinetobacter baumannii infected patients showed high serum ferritin levels ( = 0.0001). e clinical symptoms have been found with A. baumannii +ve with a mean and standard deviation of 47 (5.1%) and A. baumannii ve with mean and standard deviation of 60 (6.5%). Conclusion. Isolation of asymptomatic A. baumannii from the thalassemia patients shows an alarming situation of bacterial infections. A continuous surveillance of transfusion dependent thalassemia patients is recommended for bacterial sepsis. 1. Introduction Acinetobacter baumannii belongs to the family of gram- negative bacteria [1]. e bacteria has been mostly found in the clinical samples, particularly related to the nosocomial infections [2]. Nosocomial infections are mainly received through sinks, shower units, infusion pumps, resuscitation apparatuses, and fomites, such as pillows, mattresses, and sinks. Hospital water systems have oſten been recognized as a source of nosocomial infection principally among the patients, who are immunocompromised in critical care units [3]. Furthermore, it is also identified as the etiological factor for the blood infections in patients in critical condition [4– 6]. e hospital acquired infections are a global concern that affect a significant number of patients during treatments. More specifically, intensive care units (ICUs) tend to be contaminated with the pathogens that conveniently result in cross transmission. As the bacteria can survive and grow on dry surfaces, the contagion can also be passed by the hands of the healthcare professional and even environment [6, 7]. Acinetobacter baumannii, as a typical opportunistic pathogen, expresses a myriad of factors, which affect their pathogenicity in humans. ese elements have the ability to settle and persist clinging to solid surfaces. Also, they have the ability to be extracted from the surrounding nutrients, in particularity to iron. e bacteria work by adherence to the epithelial cells and their subsequent death by apoptosis that is preceded by the production and secretion of enzymes. ese products tend to be toxic in nature and are capable of infecting and damaging tissues. However, limited knowledge is presently known about the molecular and biochemical nature of most of these processes and factors, chiefly about the role of virulence and pathogenesis related to bacterial infections [2]. e bacterium Acinetobacter baumannii is presumed to have extensive association with the thalassemia patients due to the fact that these individuals require a regular blood transfusion for their management. is aspect makes them vulnerable to acquire infections and also develop iron Hindawi BioMed Research International Volume 2017, Article ID 2351037, 5 pages https://doi.org/10.1155/2017/2351037

Transcript of ResearchArticle Acinetobacter baumannii Infection in...

Page 1: ResearchArticle Acinetobacter baumannii Infection in ...downloads.hindawi.com/journals/bmri/2017/2351037.pdf · ResearchArticle Acinetobacter baumannii Infection in Transfusion Dependent

Research ArticleAcinetobacter baumannii Infection in Transfusion DependentThalassemia Patients with Sepsis

Muzaheed Abdul Rasheed Faisal Mousa Alzahrani and Saeed Sattar Shaikh

Department of Clinical Laboratory Science College of Applied Medical Sciences University of Dammam Dammam Saudi Arabia

Correspondence should be addressed to Muzaheed Abdul Rasheed marasheeduodedusa

Received 9 February 2017 Revised 27 April 2017 Accepted 30 April 2017 Published 17 May 2017

Academic Editor Paola Di Carlo

Copyright copy 2017 Muzaheed Abdul Rasheed et al This is an open access article distributed under the Creative CommonsAttribution License which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited

Purpose To identify the Acinetobacter baumannii infection among transfusion dependent thalassemia patients Methods Aquantitative approach was employed to assess Acinetobacter baumannii infection in transfusion dependent thalassemia patientsSamples were collected from 916 patients which have shown bacterial growth on MacConkey and blood agar culture media Abaumannii strains were identified by microbiological methods and Gramrsquos staining API 20 E kit (Biomerieux USA) was usedfor final identification Results From 916 cultured blood specimens 107 (116) showed growth of A baumannii Serum ferritinin thalassemic patients without bacterial infections was 38495 plusmn 15135 120583gL versus 64135 plusmn 21039 120583gL in those with bacterialinfections (119901 = 00001) Acinetobacter baumannii infected patients have shown higher serum ferritin levels (119901 = 00001) Serumferritin in thalassemic patients was 38495plusmn15135 120583gL versus 64135plusmn21039 120583gL in those with bacterial infections (119901 = 00001)Acinetobacter baumannii infected patients showed high serum ferritin levels (119901 = 00001) The clinical symptoms have been foundwith A baumannii +ve with a mean and standard deviation of 47 (51) and A baumannii minusve with mean and standard deviationof 60 (65) Conclusion Isolation of asymptomatic A baumannii from the thalassemia patients shows an alarming situation ofbacterial infections A continuous surveillance of transfusion dependent thalassemia patients is recommended for bacterial sepsis

1 Introduction

Acinetobacter baumannii belongs to the family of gram-negative bacteria [1] The bacteria has been mostly found inthe clinical samples particularly related to the nosocomialinfections [2] Nosocomial infections are mainly receivedthrough sinks shower units infusion pumps resuscitationapparatuses and fomites such as pillows mattresses andsinks Hospital water systems have often been recognized asa source of nosocomial infection principally among thepatients who are immunocompromised in critical care units[3] Furthermore it is also identified as the etiological factorfor the blood infections in patients in critical condition [4ndash6] The hospital acquired infections are a global concern thataffect a significant number of patients during treatmentsMore specifically intensive care units (ICUs) tend to becontaminated with the pathogens that conveniently result incross transmission As the bacteria can survive and grow ondry surfaces the contagion can also be passed by the handsof the healthcare professional and even environment [6 7]

Acinetobacter baumannii as a typical opportunisticpathogen expresses a myriad of factors which affect theirpathogenicity in humans These elements have the ability tosettle and persist clinging to solid surfaces Also they havethe ability to be extracted from the surrounding nutrientsin particularity to iron The bacteria work by adherence tothe epithelial cells and their subsequent death by apoptosisthat is preceded by the production and secretion of enzymesThese products tend to be toxic in nature and are capable ofinfecting and damaging tissues However limited knowledgeis presently known about the molecular and biochemicalnature of most of these processes and factors chiefly aboutthe role of virulence and pathogenesis related to bacterialinfections [2]

The bacterium Acinetobacter baumannii is presumed tohave extensive association with the thalassemia patients dueto the fact that these individuals require a regular bloodtransfusion for their management This aspect makes themvulnerable to acquire infections and also develop iron

HindawiBioMed Research InternationalVolume 2017 Article ID 2351037 5 pageshttpsdoiorg10115520172351037

2 BioMed Research International

overload in their body which may provide a likely envi-ronment for the bacteria to flourish [8 9] The chances forthe bacterial transmission are higher either from the con-taminated equipment or the already infected blood [10ndash12]The mortality due to the septic shock as a result of bloodinfection is one of the common observations in the cases ofthalassemia [13] As Pakistan comprises a large transfusiondependent population suffering from thalassemia there is ahuge gap for identifying the risk of bacterial contaminationin these patients Therefore the study has aimed to identifythe prevalence ofAcinetobacter baumannii infection in trans-fusion dependent thalassemia patients who have presentedwith sepsis in the region of Sindh Pakistan

2 Materials and Methods

An observational study was carried out at Diagnostic andResearch Laboratory Liaquat University ofMedical andHealthSciences (LUMHS) JamshoroHyderabad Sindh Pakistanfrom June 2015 to August 2015

21 Inclusion Criteria The patients who presented withsevere sepsis and required hospitalization management wereselected for the study from the outpatient department (OPD)The international criteria adopted for the diagnosis of sepsiswere made on the clinical and radiological findings Sepsiswas confirmed by the culture and sensitivity of blood urinestool pus or other body fluid samples It was implementedafter the identification of the possible indications that mayinclude inflammation or abscess skin wounds fever neu-tropenia shortness of breath chest andor abdominal painand backache that may relate to any recent trauma or priorinjury [14]

The incidence of Acinetobacter baumannii was correlatedto the clinical findings of iron overload as initially thecondition inclines to be asymptomatic however it mayexpress dire outcomes of organ dysfunction and even failurewhen it persists [15] The expression of symptoms has beenindicated as positive (+ve) and the absence as negative (minusve)Serum ferritin level was used as a marker of the iron excess asit tends to increase during sepsis

22 Samples A total of 916 patients were recruited into thestudy during the observational period The blood samplesfor the purpose of culture have been obtained after takingthe signed consent from the participants The blood samplewas drawn by following the standardized approach for bloodwithdrawal Specifically the approach of venipuncture wasused after the sanitization of skin through alcohol swab Atourniquet was used during the process of blood withdrawalA volume of 10ml blood was taken from the patients throughstandardized blood withdrawal techniques Moreover theblood has been withdrawn once for the investigation

23 Media Reagents and Kits

(i) MacConkey and blood agar (Oxoid Ltd CambridgeUK) medium were used for culture and sensitivity

107

809

Positive Negative

Acinetobacter baumannii (n = 916)

0100200300400500600700800900

Num

ber o

f pat

ient

s

Figure 1 Acinetobacter baumannii

(ii) Blood agar medium differentiates the hemolytic andnonhemolytic bacteria Iso-Sensitest agar medium(Oxoid Ltd Cambridge UK) was used for the deter-mination of resistance pattern against different antibi-otics groups

(iii) Isolates were identified by API 20 E kit (BiomerieuxUSA) [16]

24 Identification of Bacterial Isolates Isolates have beenidentified via standard microbiological techniques like col-ony morphology and Gramrsquos staining [16] Positivity of thecultures has been identified as the existence of infectionsthus such infections have been termed as symptomatic infec-tions Complete blood components were cultured to identifyspecified range of outcomes

25 Data Analysis The data was analyzed with SPSS 210(IBM incorporation USA) statistical package Continuousand categorical variables were analyzed by Studentrsquos 119905-testand Chi-square testing respectivelyThe covariates were alsoanalyzed through similar approach which mainly includednumber of RBCs patientsrsquo age and exposure to chelationtherapyThe difference of resistance levels of various drugs inESBL producing strains versus non-ESBL producing strainswas calculated by Fisher exact test Data was analyzed at 95confidence interval (119901 le 005)

3 Results

Out of 916 cultured blood specimens 107 (116) specimenspresented growth of A baumannii The study involved6681 of the males and 3318 of the females Majority ofthe thalassemic patients (865) were chronic transfusiondependent receiving two transfusions per week (Table 1)High serum ferritin levels were observed in the study pop-ulation as shown in Table 1 Serum ferritin in thalassemicpatients without bacterial infections was 38495plusmn15135 120583gLand 64135 plusmn 21039 120583gL in those with bacterial infections(119901 = 00001) Acinetobacter baumannii infected patientsindicated high serum ferritin levels None of the study partic-ipants had ever received iron chelation therapy The clinicalsymptoms have been found with A baumannii +ve with amean and standard deviation of 47 (51) and A baumanniiminusvewithmean and standard deviation of 60 (65) (Figure 1)

BioMed Research International 3

Table 1 Characteristics of study population (119899 = 916)

Mean plusmn SD119873 () 119901 value

Age (years) 71 plusmn 25

Male 612 (6681) 00001Female 304 (3318)First transfusion age (years) 18 plusmn 13

Years of transfusion (years) 63 plusmn 17

Frequency of transfusions(i) 1 transfusion per week 123 (1342) 00001(ii) 2 transfusions per week 793 (865)

Serum ferritin (120583gL) 49893 plusmn 19783 120583gLSerum ferritin (120583gL) with bacterial infections 38495 plusmn 15135 120583gL 00001Serum ferritin (120583gL) without bacterial infections 64135 plusmn 21039 120583gLAcinetobacter baumannii infection

(i) Positive 107 (1168) 00001(ii) Negative 809 (8831)

Clinical symptoms(i) A baumannii +ve 47 (51) 002(ii) A baumannii minusve 60 (65)

The serum ferritin has also been found statistically significant(119901 = 00001) with and without bacterial infection

4 Discussion

The present study has evaluated that there were high serumferritin levels and clinical symptoms were found with Abaumannii +ve The serum ferritin has also been foundstatistically significant with and without bacterial infectionIron overload is a usual clinical issue among patients withmajor 120573-thalassemia A study by Akhlaghpoor et al [17]assessed the occurrence of excess iron in some parts ofthe brain (basal ganglia adenohypophysis thalamus andmidbrain) among patients with 120573-thalassemia major andevaluated the relationship among serum ferritin and liveriron content Liver iron content and serum ferritin mightnot be appropriate indicators of brain iron deposition inpatients with major 120573 thalassemia It has been observed byTalsania et al [18] that patients in the corporation hospitalshad more frequency of blood transfusion as compared to thegovernment hospital Major thalassemia cases were advancedas compared to minor complications [18] Acinetobacter bau-mannii is found in the water soil and hospital environmentsin the first project reported in Sindh [19] A baumanniiis considered as a pathogen opportunistic and therefore itrarely causes infections Generally it affects the patients whoare hospitalized and underwent invasive procedures or areimmunocompromised and use antineoplastic [11]

A baumannii induced nosocomial infections includebacteremia septicemia endocarditis pneumonia woundinfections and urinary tract infections It is a cause of blood-stream infections in the intensive care setting [20] Acineto-bacter baumannii is probable to cause a variety of infectionsincluding pneumonia bacteremia peritonitis and urinary

tract infection [2]A baumannii organisms showed virulencefactors for solid and dry surfaces to sequester iron fromsurrounding adhesion to epithelial surfaces production ofgelatinase and proteinases skin colonization and ability toform biofilms for colonization and survival [21] During thelast decade treatment of these infections has become criticaldepending on the emergence of multidrug-resistant strainswhich has been associated with infection of hospital equip-ment (respirators air-conditioning swimming equipmentfor diagnostic imaging etc) [11]The emergence of resistanceto carbapenems has limited the treatment to the use ofpolymyxins which is considered as the main therapeuticoption However it has been observed that although theresistance to polymyxins is very rare in isolatedAcinetobacterclinical efficacy in the treatment of infections is not alwayssatisfactory It has been found that the biofilm synthesis dueto these bacteria on a plastic medium was stimulated by irondeficiency in surrounding conditions imposed by the ironchelator 221015840-dipyridyl (DIP) [19] Hence it was reported thatthe iron is needed for the biofilm mode of growth of Abaumannii [3]

Transfusion is an important therapy for thalassemia but itcontains risk including transfusion reactions hemosiderosisinfections and alloimmunization [22] Risk factors whichpredispose a patient for infection crab are not distinct fromother multiresistant microorganisms Patients who aremulti-invaded and underwent surgical procedure were mostaffected Wang et al [23] isolated bacteria flora fromtransfusion dependent thalassemia patientsMicroorganismsincluded K pneumoniae Acinetobacter baumannii Strepto-coccus intermedius Pseudomonas aeruginosa Vibrio vulnifi-cus Yersinia enterocolitica and Escherichia coli Wang et al[23] have reported an incidence of severe sepsis of 160infections100 subjects annually

4 BioMed Research International

The true incidence of bacterial infections in transfusiondependent thalassemic patients has been neglected in thearea of clinical research In the present study 107 (1168)specimens showed growth of A baumannii out of total 916cultured blood specimens The results are aligned with thestudy of Wang et al [23] However the results of A bauman-nii infection in transfusion dependent thalassemic patientsremained unmatched as the present study is the first researchto report from Sindh region Regular transfusions mightlead to more complicated situations like iron overload if thepatients are not treated appropriately The transmission ofHCV HBV and HCV is a main issue in the developing coun-tries where the standards of blood safety are not really highIn accordance with the findings of the study conducted byAhmed Kiani et al [24] Transfusion Transmitted Infectionswere distressingly high andHCVwas observed as the leadingTTI along with the presence of HIV in some cases

Extensively drug resistant (XDR) Acinetobacter bauman-nii (Acb) might be the source of serious infections in censo-riously ill patients There is the only therapeutic option thatis colistin that often remains helpful Adding of rifampicinto colistin might be synergistic in vitro The study assessedthat the arrangement of rifampicin and colistin will condensethe mortality of XDR Acb infections as compared to colistinalone In serious XDR Acb infections 30-day mortality is notreduced by the addition of rifampicin to colistin The resultshighlighted that the rifampicin should not be regularly jointwith colistin in clinical practice The augmented rate of Acbannihilation with amalgamation treatment might still infer aclinical benefit [25]

When a potential threat is felt by the body Fe (iron) getstransferred to ferritin to be contained so that the injuriousand damaging invader cannot get to the iron Enough iron isobtained to make the red blood cells but there is no surplusremained to nourish the injurious pathogens A person withanemia will experience a modest decline depending on theunderlying causes of disease It will take place over timeobserving the onset of inflammation because of the presenceof disease or infectionThe values of hemoglobin will reach alow and normal range of 95ndash105 gdL and remain constantTherefore anemia of chronic disease can be recognized witha serum ferritin test [26]

As iron overload occurs in thalassemia patients becauseof regular blood transfusions particularly in those withoutiron chelating therapy there are more chances of gram-negative bacterial infectionsThepresence of iron predisposesthalassemic patients to bacterial infections [3] A baumanniisequesters iron by iron carriers and stores bound with hostrsquosproteins and thus it can combat decreased level of iron inblood [27]

It was found that A baumannii shows good ability tosequester hostrsquos iron as it produces large quantities of sid-erophores for Fe (III) transport [28] Keeping in mind thekey role of iron in Acinetobacter baumannii pathogenicity[28 29] iron chelator is considered as a nonantibiotic optionto combat certain bacterial infection As the transfusionsare dependent on thalassemia patients large quantities ofiron are observed therefore it can be said that it is an idealenvironment for the A baumannii growth [2 29]

5 Conclusion

The findings of A baumannii from the thalassemia patientsare supported by the previous studies as mentioned aboveIt is identified that iron overload is one of the risk factorsfor bacterial colonization Isolation of A baumannii fromthe thalassemia patients showed an alarming situation ofbacterial infections A continuous surveillance of transfusiondependent thalassemia patients is recommended for bacterialinfections Iron chelation therapy may alleviate the iron loadin thalassemia patients

Consent

A total of 916 patients were recruited into the study and allthe participants were provided with informed consent formsto ensure the confidentiality of the data collected from them

Conflicts of Interest

The authors declare that there are no conflicts of interestregarding the publication of this paper

Acknowledgments

The authors are very thankful to Mr Mohammad Ali Diag-nostic and Research Laboratory Liaquat University of Med-ical and Health Sciences (LUMHS) JamshoroHyderabadSindh Pakistan for his technical contribution to thisresearch Dr Saeed Sattar Shaik conceptualized the idea andgathered and compiled raw data Dr Muzaheed AbdulRasheed applied relevant statistical tools and analyzed andconcluded the data Dr Faisal Mousa Alzahrani interpretedthe data and wrote the manuscript All the authors read themanuscript and contributed intellectually

References

[1] KAAl-Anazi andAMAl-Jasser ldquoInfections caused byAcine-tobacter baumannii in recipients of hematopoietic stem celltransplantationrdquo Frontiers in Oncology vol 4 article 186 2014

[2] T Foley and A Simeonov ldquoTargeting iron assimilation todevelop new antibacterialsrdquo Expert Opinion on Drug Discoveryvol 7 no 9 pp 831ndash847 2012

[3] G Suleyman and G J Alangaden ldquoNosocomial fungal infec-tionsrdquo Infectious Disease Clinics of North America vol 30 no 4pp 1023ndash1052 2016

[4] D Grimaldi L Le Bourhis B Sauneuf et al ldquoSpecific MAITcell behaviour among innate-like T lymphocytes in critically illpatients with severe infectionsrdquo Intensive CareMedicine vol 40no 2 pp 192ndash201 2014

[5] L C S Antunes P Visca and K J Towner ldquoAcinetobacter bau-mannii evolution of a global pathogenrdquo Pathogens and Diseasevol 71 no 3 pp 292ndash301 2014

[6] V Russotto A Cortegiani G Graziano et al ldquoBloodstreaminfections in intensive care unit patients distribution andantibiotic resistance of bacteriardquo Infection and Drug Resistancevol 8 pp 287ndash296 2015

[7] V Russotto A Cortegiani S M Raineri and A GiarratanoldquoBacterial contamination of inanimate surfaces and equipment

BioMed Research International 5

in the intensive care unitrdquo Journal of Intensive Care vol 3 no 12015

[8] M Ramadan and M Mohamed Ismael Fouda ldquoRelationshipbetween elevated liver enzymes with iron overload and viralhepatitis in children withb-thalassemia majorrdquo Al-Azhar AssiutMedical Journal vol 13 no 2 2015

[9] J E Cassat and E P Skaar ldquoIron in infection and immunityrdquoCell Host and Microbe vol 13 no 5 pp 509ndash519 2013

[10] J L Kwiatkowski H-Y Kim A AThompson et al ldquoChelationuse and iron burden inNorthAmerican and British thalassemiapatients a report from the thalassemia longitudinal cohortrdquoBlood vol 119 no 12 pp 2746ndash2753 2012

[11] HAnsari Saqib S Tahir AMushtaq et al ldquoMolecular epidemi-ology of szlig-thalassemia in Pakistan far reaching implicationsrdquoIndian Journal of Human Genetics vol 2 no 4 pp 403ndash4082011

[12] M G Thompson B W Corey Y Si D W Craft and D VZurawski ldquoAntibacterial activities of iron chelators againstcommon nosocomial pathogensrdquo Antimicrobial Agents andChemotherapy vol 56 no 10 pp 5419ndash5421 2012

[13] M S Paksu A Karli S Paksu A K Guney S N Ozsevik andN Belet ldquoFatal sepsis in a child with thalassemia major due toSerratia marcescensrdquo Pediatrics International vol 56 no 5 pp796-797 2014

[14] S Shrestha ldquoIdentifying and assessing patientrsquos sepsis by nursesin an emergency department a literature reviewrdquo 2016

[15] P Gujja D R Rosing D J Tripodi and Y Shizukuda ldquoIronoverload cardiomyopathy better understanding of an increas-ing disorderrdquo Journal of the American College of Cardiology vol56 no 13 pp 1001ndash1012 2010

[16] D M Guerrero F Perez N G Conger et al ldquoAcinetobacterbaumannii-associated skin and soft tissue infections recogniz-ing a broadening spectrum of diseaserdquo Surgical Infections vol11 no 1 pp 49ndash57 2010

[17] S Akhlaghpoor A Ghahari A Morteza O Khalilzadeh AShakourirad and M R Alinaghizadeh ldquoQuantitative T2 mag-netic resonance imaging for evaluation of iron deposition in thebrain of 120573-thalassemia patientsrdquo Clinical Neuroradiology vol22 no 3 pp 211ndash217 2012

[18] S Talsania N Talsania and N Himanshu ldquoA cross sectionalstudy of thalassemia in Ahmedabad City Gujarat (hospitalbased)rdquo Healthline Journal of Indian Association of Preventiveand Social Medicine vol 2 no 1 pp 48ndash51 2011

[19] S Begum F Hasan S Hussain and A A Shah ldquoPrevalenceof multi drug resistant Acinetobacter baumannii in the clinicalsamples from tertiary care hospital in Islamabad PakistanrdquoPakistan Journal ofMedical Sciences vol 29 no 5 pp 1253ndash12582013

[20] M J McConnell L Actis and J Pachon ldquoAcinetobacter bau-mannii human infections factors contributing to pathogenesisand animal modelsrdquo FEMS Microbiology Reviews vol 37 no 2pp 130ndash155 2013

[21] M Eveillard M Kempf O Belmonte H Pailhories andM-L Joly-Guillou ldquoReservoirs of Acinetobacter baumanniioutside the hospital and potential involvement in emerginghuman community-acquired infectionsrdquo International Journalof Infectious Diseases vol 17 no 10 pp e802-e805 2013

[22] E Vichinsky L Neumayr S Trimble et al ldquoTransfusion com-plications in thalassemia patients a report from the Centers forDisease Control and Prevention (CME)rdquo Transfusion vol 54no 4 pp 972ndash981 2014

[23] S-C Wang K-H Lin J P S Chern et al ldquoSevere bacterialinfection in transfusion-dependent patients with thalassemiamajorrdquo Clinical Infectious Diseases vol 37 no 7 pp 984ndash9882003

[24] R Ahmed Kiani M Anwar U Waheed M J Asad S Abbasiand H Abbas Zaheer ldquoEpidemiology of transfusion transmit-ted infection among patients with 120573-thalassaemia major inPakistanrdquo Journal of Blood Transfusion vol 2016 Article ID8135649 5 pages 2016

[25] E Durante-Mangoni G Signoriello R Andini et al ldquoColistinand rifampicin compared with colistin alone for the treatmentof serious infections due to extensively drug-resistant Acine-tobacter baumannii a multicenter randomized clinical trialrdquoClinical Infectious Diseases vol 57 no 3 pp 349ndash358 2013

[26] N Filmann J Rey and S Schneeweiss ldquoPrevalence of anemiain inflammatory bowel diseases in European countries asystematic review and individual patient data meta-analysisrdquoInflammatory Bowel Diseases vol 20 no 5 pp 936ndash945 2014

[27] L C S Antunes F Imperi K J Towner and P Visca ldquoGenome-assisted identification of putative iron-utilization genes inAcinetobacter baumannii and their distribution among a geno-typically diverse collection of clinical isolatesrdquo Research inMicrobiology vol 162 no 3 pp 279ndash284 2011

[28] B L Mortensen and E P Skaar ldquoThe contribution of nutrientmetal acquisition and metabolism to Acinetobacter baumanniisurvival within the hostrdquo Frontiers in Cellular and InfectionMicrobiology vol 3 Article ID 00095 2013

[29] L De Leseleuc G Harris R KuoLee and W Chen ldquoIn vitroand in vivo biological activities of iron chelators and galliumnitrate against Acinetobacter baumanniirdquo Antimicrobial Agentsand Chemotherapy vol 56 no 10 pp 5397ndash5400 2012

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Page 2: ResearchArticle Acinetobacter baumannii Infection in ...downloads.hindawi.com/journals/bmri/2017/2351037.pdf · ResearchArticle Acinetobacter baumannii Infection in Transfusion Dependent

2 BioMed Research International

overload in their body which may provide a likely envi-ronment for the bacteria to flourish [8 9] The chances forthe bacterial transmission are higher either from the con-taminated equipment or the already infected blood [10ndash12]The mortality due to the septic shock as a result of bloodinfection is one of the common observations in the cases ofthalassemia [13] As Pakistan comprises a large transfusiondependent population suffering from thalassemia there is ahuge gap for identifying the risk of bacterial contaminationin these patients Therefore the study has aimed to identifythe prevalence ofAcinetobacter baumannii infection in trans-fusion dependent thalassemia patients who have presentedwith sepsis in the region of Sindh Pakistan

2 Materials and Methods

An observational study was carried out at Diagnostic andResearch Laboratory Liaquat University ofMedical andHealthSciences (LUMHS) JamshoroHyderabad Sindh Pakistanfrom June 2015 to August 2015

21 Inclusion Criteria The patients who presented withsevere sepsis and required hospitalization management wereselected for the study from the outpatient department (OPD)The international criteria adopted for the diagnosis of sepsiswere made on the clinical and radiological findings Sepsiswas confirmed by the culture and sensitivity of blood urinestool pus or other body fluid samples It was implementedafter the identification of the possible indications that mayinclude inflammation or abscess skin wounds fever neu-tropenia shortness of breath chest andor abdominal painand backache that may relate to any recent trauma or priorinjury [14]

The incidence of Acinetobacter baumannii was correlatedto the clinical findings of iron overload as initially thecondition inclines to be asymptomatic however it mayexpress dire outcomes of organ dysfunction and even failurewhen it persists [15] The expression of symptoms has beenindicated as positive (+ve) and the absence as negative (minusve)Serum ferritin level was used as a marker of the iron excess asit tends to increase during sepsis

22 Samples A total of 916 patients were recruited into thestudy during the observational period The blood samplesfor the purpose of culture have been obtained after takingthe signed consent from the participants The blood samplewas drawn by following the standardized approach for bloodwithdrawal Specifically the approach of venipuncture wasused after the sanitization of skin through alcohol swab Atourniquet was used during the process of blood withdrawalA volume of 10ml blood was taken from the patients throughstandardized blood withdrawal techniques Moreover theblood has been withdrawn once for the investigation

23 Media Reagents and Kits

(i) MacConkey and blood agar (Oxoid Ltd CambridgeUK) medium were used for culture and sensitivity

107

809

Positive Negative

Acinetobacter baumannii (n = 916)

0100200300400500600700800900

Num

ber o

f pat

ient

s

Figure 1 Acinetobacter baumannii

(ii) Blood agar medium differentiates the hemolytic andnonhemolytic bacteria Iso-Sensitest agar medium(Oxoid Ltd Cambridge UK) was used for the deter-mination of resistance pattern against different antibi-otics groups

(iii) Isolates were identified by API 20 E kit (BiomerieuxUSA) [16]

24 Identification of Bacterial Isolates Isolates have beenidentified via standard microbiological techniques like col-ony morphology and Gramrsquos staining [16] Positivity of thecultures has been identified as the existence of infectionsthus such infections have been termed as symptomatic infec-tions Complete blood components were cultured to identifyspecified range of outcomes

25 Data Analysis The data was analyzed with SPSS 210(IBM incorporation USA) statistical package Continuousand categorical variables were analyzed by Studentrsquos 119905-testand Chi-square testing respectivelyThe covariates were alsoanalyzed through similar approach which mainly includednumber of RBCs patientsrsquo age and exposure to chelationtherapyThe difference of resistance levels of various drugs inESBL producing strains versus non-ESBL producing strainswas calculated by Fisher exact test Data was analyzed at 95confidence interval (119901 le 005)

3 Results

Out of 916 cultured blood specimens 107 (116) specimenspresented growth of A baumannii The study involved6681 of the males and 3318 of the females Majority ofthe thalassemic patients (865) were chronic transfusiondependent receiving two transfusions per week (Table 1)High serum ferritin levels were observed in the study pop-ulation as shown in Table 1 Serum ferritin in thalassemicpatients without bacterial infections was 38495plusmn15135 120583gLand 64135 plusmn 21039 120583gL in those with bacterial infections(119901 = 00001) Acinetobacter baumannii infected patientsindicated high serum ferritin levels None of the study partic-ipants had ever received iron chelation therapy The clinicalsymptoms have been found with A baumannii +ve with amean and standard deviation of 47 (51) and A baumanniiminusvewithmean and standard deviation of 60 (65) (Figure 1)

BioMed Research International 3

Table 1 Characteristics of study population (119899 = 916)

Mean plusmn SD119873 () 119901 value

Age (years) 71 plusmn 25

Male 612 (6681) 00001Female 304 (3318)First transfusion age (years) 18 plusmn 13

Years of transfusion (years) 63 plusmn 17

Frequency of transfusions(i) 1 transfusion per week 123 (1342) 00001(ii) 2 transfusions per week 793 (865)

Serum ferritin (120583gL) 49893 plusmn 19783 120583gLSerum ferritin (120583gL) with bacterial infections 38495 plusmn 15135 120583gL 00001Serum ferritin (120583gL) without bacterial infections 64135 plusmn 21039 120583gLAcinetobacter baumannii infection

(i) Positive 107 (1168) 00001(ii) Negative 809 (8831)

Clinical symptoms(i) A baumannii +ve 47 (51) 002(ii) A baumannii minusve 60 (65)

The serum ferritin has also been found statistically significant(119901 = 00001) with and without bacterial infection

4 Discussion

The present study has evaluated that there were high serumferritin levels and clinical symptoms were found with Abaumannii +ve The serum ferritin has also been foundstatistically significant with and without bacterial infectionIron overload is a usual clinical issue among patients withmajor 120573-thalassemia A study by Akhlaghpoor et al [17]assessed the occurrence of excess iron in some parts ofthe brain (basal ganglia adenohypophysis thalamus andmidbrain) among patients with 120573-thalassemia major andevaluated the relationship among serum ferritin and liveriron content Liver iron content and serum ferritin mightnot be appropriate indicators of brain iron deposition inpatients with major 120573 thalassemia It has been observed byTalsania et al [18] that patients in the corporation hospitalshad more frequency of blood transfusion as compared to thegovernment hospital Major thalassemia cases were advancedas compared to minor complications [18] Acinetobacter bau-mannii is found in the water soil and hospital environmentsin the first project reported in Sindh [19] A baumanniiis considered as a pathogen opportunistic and therefore itrarely causes infections Generally it affects the patients whoare hospitalized and underwent invasive procedures or areimmunocompromised and use antineoplastic [11]

A baumannii induced nosocomial infections includebacteremia septicemia endocarditis pneumonia woundinfections and urinary tract infections It is a cause of blood-stream infections in the intensive care setting [20] Acineto-bacter baumannii is probable to cause a variety of infectionsincluding pneumonia bacteremia peritonitis and urinary

tract infection [2]A baumannii organisms showed virulencefactors for solid and dry surfaces to sequester iron fromsurrounding adhesion to epithelial surfaces production ofgelatinase and proteinases skin colonization and ability toform biofilms for colonization and survival [21] During thelast decade treatment of these infections has become criticaldepending on the emergence of multidrug-resistant strainswhich has been associated with infection of hospital equip-ment (respirators air-conditioning swimming equipmentfor diagnostic imaging etc) [11]The emergence of resistanceto carbapenems has limited the treatment to the use ofpolymyxins which is considered as the main therapeuticoption However it has been observed that although theresistance to polymyxins is very rare in isolatedAcinetobacterclinical efficacy in the treatment of infections is not alwayssatisfactory It has been found that the biofilm synthesis dueto these bacteria on a plastic medium was stimulated by irondeficiency in surrounding conditions imposed by the ironchelator 221015840-dipyridyl (DIP) [19] Hence it was reported thatthe iron is needed for the biofilm mode of growth of Abaumannii [3]

Transfusion is an important therapy for thalassemia but itcontains risk including transfusion reactions hemosiderosisinfections and alloimmunization [22] Risk factors whichpredispose a patient for infection crab are not distinct fromother multiresistant microorganisms Patients who aremulti-invaded and underwent surgical procedure were mostaffected Wang et al [23] isolated bacteria flora fromtransfusion dependent thalassemia patientsMicroorganismsincluded K pneumoniae Acinetobacter baumannii Strepto-coccus intermedius Pseudomonas aeruginosa Vibrio vulnifi-cus Yersinia enterocolitica and Escherichia coli Wang et al[23] have reported an incidence of severe sepsis of 160infections100 subjects annually

4 BioMed Research International

The true incidence of bacterial infections in transfusiondependent thalassemic patients has been neglected in thearea of clinical research In the present study 107 (1168)specimens showed growth of A baumannii out of total 916cultured blood specimens The results are aligned with thestudy of Wang et al [23] However the results of A bauman-nii infection in transfusion dependent thalassemic patientsremained unmatched as the present study is the first researchto report from Sindh region Regular transfusions mightlead to more complicated situations like iron overload if thepatients are not treated appropriately The transmission ofHCV HBV and HCV is a main issue in the developing coun-tries where the standards of blood safety are not really highIn accordance with the findings of the study conducted byAhmed Kiani et al [24] Transfusion Transmitted Infectionswere distressingly high andHCVwas observed as the leadingTTI along with the presence of HIV in some cases

Extensively drug resistant (XDR) Acinetobacter bauman-nii (Acb) might be the source of serious infections in censo-riously ill patients There is the only therapeutic option thatis colistin that often remains helpful Adding of rifampicinto colistin might be synergistic in vitro The study assessedthat the arrangement of rifampicin and colistin will condensethe mortality of XDR Acb infections as compared to colistinalone In serious XDR Acb infections 30-day mortality is notreduced by the addition of rifampicin to colistin The resultshighlighted that the rifampicin should not be regularly jointwith colistin in clinical practice The augmented rate of Acbannihilation with amalgamation treatment might still infer aclinical benefit [25]

When a potential threat is felt by the body Fe (iron) getstransferred to ferritin to be contained so that the injuriousand damaging invader cannot get to the iron Enough iron isobtained to make the red blood cells but there is no surplusremained to nourish the injurious pathogens A person withanemia will experience a modest decline depending on theunderlying causes of disease It will take place over timeobserving the onset of inflammation because of the presenceof disease or infectionThe values of hemoglobin will reach alow and normal range of 95ndash105 gdL and remain constantTherefore anemia of chronic disease can be recognized witha serum ferritin test [26]

As iron overload occurs in thalassemia patients becauseof regular blood transfusions particularly in those withoutiron chelating therapy there are more chances of gram-negative bacterial infectionsThepresence of iron predisposesthalassemic patients to bacterial infections [3] A baumanniisequesters iron by iron carriers and stores bound with hostrsquosproteins and thus it can combat decreased level of iron inblood [27]

It was found that A baumannii shows good ability tosequester hostrsquos iron as it produces large quantities of sid-erophores for Fe (III) transport [28] Keeping in mind thekey role of iron in Acinetobacter baumannii pathogenicity[28 29] iron chelator is considered as a nonantibiotic optionto combat certain bacterial infection As the transfusionsare dependent on thalassemia patients large quantities ofiron are observed therefore it can be said that it is an idealenvironment for the A baumannii growth [2 29]

5 Conclusion

The findings of A baumannii from the thalassemia patientsare supported by the previous studies as mentioned aboveIt is identified that iron overload is one of the risk factorsfor bacterial colonization Isolation of A baumannii fromthe thalassemia patients showed an alarming situation ofbacterial infections A continuous surveillance of transfusiondependent thalassemia patients is recommended for bacterialinfections Iron chelation therapy may alleviate the iron loadin thalassemia patients

Consent

A total of 916 patients were recruited into the study and allthe participants were provided with informed consent formsto ensure the confidentiality of the data collected from them

Conflicts of Interest

The authors declare that there are no conflicts of interestregarding the publication of this paper

Acknowledgments

The authors are very thankful to Mr Mohammad Ali Diag-nostic and Research Laboratory Liaquat University of Med-ical and Health Sciences (LUMHS) JamshoroHyderabadSindh Pakistan for his technical contribution to thisresearch Dr Saeed Sattar Shaik conceptualized the idea andgathered and compiled raw data Dr Muzaheed AbdulRasheed applied relevant statistical tools and analyzed andconcluded the data Dr Faisal Mousa Alzahrani interpretedthe data and wrote the manuscript All the authors read themanuscript and contributed intellectually

References

[1] KAAl-Anazi andAMAl-Jasser ldquoInfections caused byAcine-tobacter baumannii in recipients of hematopoietic stem celltransplantationrdquo Frontiers in Oncology vol 4 article 186 2014

[2] T Foley and A Simeonov ldquoTargeting iron assimilation todevelop new antibacterialsrdquo Expert Opinion on Drug Discoveryvol 7 no 9 pp 831ndash847 2012

[3] G Suleyman and G J Alangaden ldquoNosocomial fungal infec-tionsrdquo Infectious Disease Clinics of North America vol 30 no 4pp 1023ndash1052 2016

[4] D Grimaldi L Le Bourhis B Sauneuf et al ldquoSpecific MAITcell behaviour among innate-like T lymphocytes in critically illpatients with severe infectionsrdquo Intensive CareMedicine vol 40no 2 pp 192ndash201 2014

[5] L C S Antunes P Visca and K J Towner ldquoAcinetobacter bau-mannii evolution of a global pathogenrdquo Pathogens and Diseasevol 71 no 3 pp 292ndash301 2014

[6] V Russotto A Cortegiani G Graziano et al ldquoBloodstreaminfections in intensive care unit patients distribution andantibiotic resistance of bacteriardquo Infection and Drug Resistancevol 8 pp 287ndash296 2015

[7] V Russotto A Cortegiani S M Raineri and A GiarratanoldquoBacterial contamination of inanimate surfaces and equipment

BioMed Research International 5

in the intensive care unitrdquo Journal of Intensive Care vol 3 no 12015

[8] M Ramadan and M Mohamed Ismael Fouda ldquoRelationshipbetween elevated liver enzymes with iron overload and viralhepatitis in children withb-thalassemia majorrdquo Al-Azhar AssiutMedical Journal vol 13 no 2 2015

[9] J E Cassat and E P Skaar ldquoIron in infection and immunityrdquoCell Host and Microbe vol 13 no 5 pp 509ndash519 2013

[10] J L Kwiatkowski H-Y Kim A AThompson et al ldquoChelationuse and iron burden inNorthAmerican and British thalassemiapatients a report from the thalassemia longitudinal cohortrdquoBlood vol 119 no 12 pp 2746ndash2753 2012

[11] HAnsari Saqib S Tahir AMushtaq et al ldquoMolecular epidemi-ology of szlig-thalassemia in Pakistan far reaching implicationsrdquoIndian Journal of Human Genetics vol 2 no 4 pp 403ndash4082011

[12] M G Thompson B W Corey Y Si D W Craft and D VZurawski ldquoAntibacterial activities of iron chelators againstcommon nosocomial pathogensrdquo Antimicrobial Agents andChemotherapy vol 56 no 10 pp 5419ndash5421 2012

[13] M S Paksu A Karli S Paksu A K Guney S N Ozsevik andN Belet ldquoFatal sepsis in a child with thalassemia major due toSerratia marcescensrdquo Pediatrics International vol 56 no 5 pp796-797 2014

[14] S Shrestha ldquoIdentifying and assessing patientrsquos sepsis by nursesin an emergency department a literature reviewrdquo 2016

[15] P Gujja D R Rosing D J Tripodi and Y Shizukuda ldquoIronoverload cardiomyopathy better understanding of an increas-ing disorderrdquo Journal of the American College of Cardiology vol56 no 13 pp 1001ndash1012 2010

[16] D M Guerrero F Perez N G Conger et al ldquoAcinetobacterbaumannii-associated skin and soft tissue infections recogniz-ing a broadening spectrum of diseaserdquo Surgical Infections vol11 no 1 pp 49ndash57 2010

[17] S Akhlaghpoor A Ghahari A Morteza O Khalilzadeh AShakourirad and M R Alinaghizadeh ldquoQuantitative T2 mag-netic resonance imaging for evaluation of iron deposition in thebrain of 120573-thalassemia patientsrdquo Clinical Neuroradiology vol22 no 3 pp 211ndash217 2012

[18] S Talsania N Talsania and N Himanshu ldquoA cross sectionalstudy of thalassemia in Ahmedabad City Gujarat (hospitalbased)rdquo Healthline Journal of Indian Association of Preventiveand Social Medicine vol 2 no 1 pp 48ndash51 2011

[19] S Begum F Hasan S Hussain and A A Shah ldquoPrevalenceof multi drug resistant Acinetobacter baumannii in the clinicalsamples from tertiary care hospital in Islamabad PakistanrdquoPakistan Journal ofMedical Sciences vol 29 no 5 pp 1253ndash12582013

[20] M J McConnell L Actis and J Pachon ldquoAcinetobacter bau-mannii human infections factors contributing to pathogenesisand animal modelsrdquo FEMS Microbiology Reviews vol 37 no 2pp 130ndash155 2013

[21] M Eveillard M Kempf O Belmonte H Pailhories andM-L Joly-Guillou ldquoReservoirs of Acinetobacter baumanniioutside the hospital and potential involvement in emerginghuman community-acquired infectionsrdquo International Journalof Infectious Diseases vol 17 no 10 pp e802-e805 2013

[22] E Vichinsky L Neumayr S Trimble et al ldquoTransfusion com-plications in thalassemia patients a report from the Centers forDisease Control and Prevention (CME)rdquo Transfusion vol 54no 4 pp 972ndash981 2014

[23] S-C Wang K-H Lin J P S Chern et al ldquoSevere bacterialinfection in transfusion-dependent patients with thalassemiamajorrdquo Clinical Infectious Diseases vol 37 no 7 pp 984ndash9882003

[24] R Ahmed Kiani M Anwar U Waheed M J Asad S Abbasiand H Abbas Zaheer ldquoEpidemiology of transfusion transmit-ted infection among patients with 120573-thalassaemia major inPakistanrdquo Journal of Blood Transfusion vol 2016 Article ID8135649 5 pages 2016

[25] E Durante-Mangoni G Signoriello R Andini et al ldquoColistinand rifampicin compared with colistin alone for the treatmentof serious infections due to extensively drug-resistant Acine-tobacter baumannii a multicenter randomized clinical trialrdquoClinical Infectious Diseases vol 57 no 3 pp 349ndash358 2013

[26] N Filmann J Rey and S Schneeweiss ldquoPrevalence of anemiain inflammatory bowel diseases in European countries asystematic review and individual patient data meta-analysisrdquoInflammatory Bowel Diseases vol 20 no 5 pp 936ndash945 2014

[27] L C S Antunes F Imperi K J Towner and P Visca ldquoGenome-assisted identification of putative iron-utilization genes inAcinetobacter baumannii and their distribution among a geno-typically diverse collection of clinical isolatesrdquo Research inMicrobiology vol 162 no 3 pp 279ndash284 2011

[28] B L Mortensen and E P Skaar ldquoThe contribution of nutrientmetal acquisition and metabolism to Acinetobacter baumanniisurvival within the hostrdquo Frontiers in Cellular and InfectionMicrobiology vol 3 Article ID 00095 2013

[29] L De Leseleuc G Harris R KuoLee and W Chen ldquoIn vitroand in vivo biological activities of iron chelators and galliumnitrate against Acinetobacter baumanniirdquo Antimicrobial Agentsand Chemotherapy vol 56 no 10 pp 5397ndash5400 2012

Submit your manuscripts athttpswwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 201

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Molecular Biology International

GenomicsInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Signal TransductionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Evolutionary BiologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Genetics Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Virolog y

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Nucleic AcidsJournal of

Volume 2014

Stem CellsInternational

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Enzyme Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Microbiology

Page 3: ResearchArticle Acinetobacter baumannii Infection in ...downloads.hindawi.com/journals/bmri/2017/2351037.pdf · ResearchArticle Acinetobacter baumannii Infection in Transfusion Dependent

BioMed Research International 3

Table 1 Characteristics of study population (119899 = 916)

Mean plusmn SD119873 () 119901 value

Age (years) 71 plusmn 25

Male 612 (6681) 00001Female 304 (3318)First transfusion age (years) 18 plusmn 13

Years of transfusion (years) 63 plusmn 17

Frequency of transfusions(i) 1 transfusion per week 123 (1342) 00001(ii) 2 transfusions per week 793 (865)

Serum ferritin (120583gL) 49893 plusmn 19783 120583gLSerum ferritin (120583gL) with bacterial infections 38495 plusmn 15135 120583gL 00001Serum ferritin (120583gL) without bacterial infections 64135 plusmn 21039 120583gLAcinetobacter baumannii infection

(i) Positive 107 (1168) 00001(ii) Negative 809 (8831)

Clinical symptoms(i) A baumannii +ve 47 (51) 002(ii) A baumannii minusve 60 (65)

The serum ferritin has also been found statistically significant(119901 = 00001) with and without bacterial infection

4 Discussion

The present study has evaluated that there were high serumferritin levels and clinical symptoms were found with Abaumannii +ve The serum ferritin has also been foundstatistically significant with and without bacterial infectionIron overload is a usual clinical issue among patients withmajor 120573-thalassemia A study by Akhlaghpoor et al [17]assessed the occurrence of excess iron in some parts ofthe brain (basal ganglia adenohypophysis thalamus andmidbrain) among patients with 120573-thalassemia major andevaluated the relationship among serum ferritin and liveriron content Liver iron content and serum ferritin mightnot be appropriate indicators of brain iron deposition inpatients with major 120573 thalassemia It has been observed byTalsania et al [18] that patients in the corporation hospitalshad more frequency of blood transfusion as compared to thegovernment hospital Major thalassemia cases were advancedas compared to minor complications [18] Acinetobacter bau-mannii is found in the water soil and hospital environmentsin the first project reported in Sindh [19] A baumanniiis considered as a pathogen opportunistic and therefore itrarely causes infections Generally it affects the patients whoare hospitalized and underwent invasive procedures or areimmunocompromised and use antineoplastic [11]

A baumannii induced nosocomial infections includebacteremia septicemia endocarditis pneumonia woundinfections and urinary tract infections It is a cause of blood-stream infections in the intensive care setting [20] Acineto-bacter baumannii is probable to cause a variety of infectionsincluding pneumonia bacteremia peritonitis and urinary

tract infection [2]A baumannii organisms showed virulencefactors for solid and dry surfaces to sequester iron fromsurrounding adhesion to epithelial surfaces production ofgelatinase and proteinases skin colonization and ability toform biofilms for colonization and survival [21] During thelast decade treatment of these infections has become criticaldepending on the emergence of multidrug-resistant strainswhich has been associated with infection of hospital equip-ment (respirators air-conditioning swimming equipmentfor diagnostic imaging etc) [11]The emergence of resistanceto carbapenems has limited the treatment to the use ofpolymyxins which is considered as the main therapeuticoption However it has been observed that although theresistance to polymyxins is very rare in isolatedAcinetobacterclinical efficacy in the treatment of infections is not alwayssatisfactory It has been found that the biofilm synthesis dueto these bacteria on a plastic medium was stimulated by irondeficiency in surrounding conditions imposed by the ironchelator 221015840-dipyridyl (DIP) [19] Hence it was reported thatthe iron is needed for the biofilm mode of growth of Abaumannii [3]

Transfusion is an important therapy for thalassemia but itcontains risk including transfusion reactions hemosiderosisinfections and alloimmunization [22] Risk factors whichpredispose a patient for infection crab are not distinct fromother multiresistant microorganisms Patients who aremulti-invaded and underwent surgical procedure were mostaffected Wang et al [23] isolated bacteria flora fromtransfusion dependent thalassemia patientsMicroorganismsincluded K pneumoniae Acinetobacter baumannii Strepto-coccus intermedius Pseudomonas aeruginosa Vibrio vulnifi-cus Yersinia enterocolitica and Escherichia coli Wang et al[23] have reported an incidence of severe sepsis of 160infections100 subjects annually

4 BioMed Research International

The true incidence of bacterial infections in transfusiondependent thalassemic patients has been neglected in thearea of clinical research In the present study 107 (1168)specimens showed growth of A baumannii out of total 916cultured blood specimens The results are aligned with thestudy of Wang et al [23] However the results of A bauman-nii infection in transfusion dependent thalassemic patientsremained unmatched as the present study is the first researchto report from Sindh region Regular transfusions mightlead to more complicated situations like iron overload if thepatients are not treated appropriately The transmission ofHCV HBV and HCV is a main issue in the developing coun-tries where the standards of blood safety are not really highIn accordance with the findings of the study conducted byAhmed Kiani et al [24] Transfusion Transmitted Infectionswere distressingly high andHCVwas observed as the leadingTTI along with the presence of HIV in some cases

Extensively drug resistant (XDR) Acinetobacter bauman-nii (Acb) might be the source of serious infections in censo-riously ill patients There is the only therapeutic option thatis colistin that often remains helpful Adding of rifampicinto colistin might be synergistic in vitro The study assessedthat the arrangement of rifampicin and colistin will condensethe mortality of XDR Acb infections as compared to colistinalone In serious XDR Acb infections 30-day mortality is notreduced by the addition of rifampicin to colistin The resultshighlighted that the rifampicin should not be regularly jointwith colistin in clinical practice The augmented rate of Acbannihilation with amalgamation treatment might still infer aclinical benefit [25]

When a potential threat is felt by the body Fe (iron) getstransferred to ferritin to be contained so that the injuriousand damaging invader cannot get to the iron Enough iron isobtained to make the red blood cells but there is no surplusremained to nourish the injurious pathogens A person withanemia will experience a modest decline depending on theunderlying causes of disease It will take place over timeobserving the onset of inflammation because of the presenceof disease or infectionThe values of hemoglobin will reach alow and normal range of 95ndash105 gdL and remain constantTherefore anemia of chronic disease can be recognized witha serum ferritin test [26]

As iron overload occurs in thalassemia patients becauseof regular blood transfusions particularly in those withoutiron chelating therapy there are more chances of gram-negative bacterial infectionsThepresence of iron predisposesthalassemic patients to bacterial infections [3] A baumanniisequesters iron by iron carriers and stores bound with hostrsquosproteins and thus it can combat decreased level of iron inblood [27]

It was found that A baumannii shows good ability tosequester hostrsquos iron as it produces large quantities of sid-erophores for Fe (III) transport [28] Keeping in mind thekey role of iron in Acinetobacter baumannii pathogenicity[28 29] iron chelator is considered as a nonantibiotic optionto combat certain bacterial infection As the transfusionsare dependent on thalassemia patients large quantities ofiron are observed therefore it can be said that it is an idealenvironment for the A baumannii growth [2 29]

5 Conclusion

The findings of A baumannii from the thalassemia patientsare supported by the previous studies as mentioned aboveIt is identified that iron overload is one of the risk factorsfor bacterial colonization Isolation of A baumannii fromthe thalassemia patients showed an alarming situation ofbacterial infections A continuous surveillance of transfusiondependent thalassemia patients is recommended for bacterialinfections Iron chelation therapy may alleviate the iron loadin thalassemia patients

Consent

A total of 916 patients were recruited into the study and allthe participants were provided with informed consent formsto ensure the confidentiality of the data collected from them

Conflicts of Interest

The authors declare that there are no conflicts of interestregarding the publication of this paper

Acknowledgments

The authors are very thankful to Mr Mohammad Ali Diag-nostic and Research Laboratory Liaquat University of Med-ical and Health Sciences (LUMHS) JamshoroHyderabadSindh Pakistan for his technical contribution to thisresearch Dr Saeed Sattar Shaik conceptualized the idea andgathered and compiled raw data Dr Muzaheed AbdulRasheed applied relevant statistical tools and analyzed andconcluded the data Dr Faisal Mousa Alzahrani interpretedthe data and wrote the manuscript All the authors read themanuscript and contributed intellectually

References

[1] KAAl-Anazi andAMAl-Jasser ldquoInfections caused byAcine-tobacter baumannii in recipients of hematopoietic stem celltransplantationrdquo Frontiers in Oncology vol 4 article 186 2014

[2] T Foley and A Simeonov ldquoTargeting iron assimilation todevelop new antibacterialsrdquo Expert Opinion on Drug Discoveryvol 7 no 9 pp 831ndash847 2012

[3] G Suleyman and G J Alangaden ldquoNosocomial fungal infec-tionsrdquo Infectious Disease Clinics of North America vol 30 no 4pp 1023ndash1052 2016

[4] D Grimaldi L Le Bourhis B Sauneuf et al ldquoSpecific MAITcell behaviour among innate-like T lymphocytes in critically illpatients with severe infectionsrdquo Intensive CareMedicine vol 40no 2 pp 192ndash201 2014

[5] L C S Antunes P Visca and K J Towner ldquoAcinetobacter bau-mannii evolution of a global pathogenrdquo Pathogens and Diseasevol 71 no 3 pp 292ndash301 2014

[6] V Russotto A Cortegiani G Graziano et al ldquoBloodstreaminfections in intensive care unit patients distribution andantibiotic resistance of bacteriardquo Infection and Drug Resistancevol 8 pp 287ndash296 2015

[7] V Russotto A Cortegiani S M Raineri and A GiarratanoldquoBacterial contamination of inanimate surfaces and equipment

BioMed Research International 5

in the intensive care unitrdquo Journal of Intensive Care vol 3 no 12015

[8] M Ramadan and M Mohamed Ismael Fouda ldquoRelationshipbetween elevated liver enzymes with iron overload and viralhepatitis in children withb-thalassemia majorrdquo Al-Azhar AssiutMedical Journal vol 13 no 2 2015

[9] J E Cassat and E P Skaar ldquoIron in infection and immunityrdquoCell Host and Microbe vol 13 no 5 pp 509ndash519 2013

[10] J L Kwiatkowski H-Y Kim A AThompson et al ldquoChelationuse and iron burden inNorthAmerican and British thalassemiapatients a report from the thalassemia longitudinal cohortrdquoBlood vol 119 no 12 pp 2746ndash2753 2012

[11] HAnsari Saqib S Tahir AMushtaq et al ldquoMolecular epidemi-ology of szlig-thalassemia in Pakistan far reaching implicationsrdquoIndian Journal of Human Genetics vol 2 no 4 pp 403ndash4082011

[12] M G Thompson B W Corey Y Si D W Craft and D VZurawski ldquoAntibacterial activities of iron chelators againstcommon nosocomial pathogensrdquo Antimicrobial Agents andChemotherapy vol 56 no 10 pp 5419ndash5421 2012

[13] M S Paksu A Karli S Paksu A K Guney S N Ozsevik andN Belet ldquoFatal sepsis in a child with thalassemia major due toSerratia marcescensrdquo Pediatrics International vol 56 no 5 pp796-797 2014

[14] S Shrestha ldquoIdentifying and assessing patientrsquos sepsis by nursesin an emergency department a literature reviewrdquo 2016

[15] P Gujja D R Rosing D J Tripodi and Y Shizukuda ldquoIronoverload cardiomyopathy better understanding of an increas-ing disorderrdquo Journal of the American College of Cardiology vol56 no 13 pp 1001ndash1012 2010

[16] D M Guerrero F Perez N G Conger et al ldquoAcinetobacterbaumannii-associated skin and soft tissue infections recogniz-ing a broadening spectrum of diseaserdquo Surgical Infections vol11 no 1 pp 49ndash57 2010

[17] S Akhlaghpoor A Ghahari A Morteza O Khalilzadeh AShakourirad and M R Alinaghizadeh ldquoQuantitative T2 mag-netic resonance imaging for evaluation of iron deposition in thebrain of 120573-thalassemia patientsrdquo Clinical Neuroradiology vol22 no 3 pp 211ndash217 2012

[18] S Talsania N Talsania and N Himanshu ldquoA cross sectionalstudy of thalassemia in Ahmedabad City Gujarat (hospitalbased)rdquo Healthline Journal of Indian Association of Preventiveand Social Medicine vol 2 no 1 pp 48ndash51 2011

[19] S Begum F Hasan S Hussain and A A Shah ldquoPrevalenceof multi drug resistant Acinetobacter baumannii in the clinicalsamples from tertiary care hospital in Islamabad PakistanrdquoPakistan Journal ofMedical Sciences vol 29 no 5 pp 1253ndash12582013

[20] M J McConnell L Actis and J Pachon ldquoAcinetobacter bau-mannii human infections factors contributing to pathogenesisand animal modelsrdquo FEMS Microbiology Reviews vol 37 no 2pp 130ndash155 2013

[21] M Eveillard M Kempf O Belmonte H Pailhories andM-L Joly-Guillou ldquoReservoirs of Acinetobacter baumanniioutside the hospital and potential involvement in emerginghuman community-acquired infectionsrdquo International Journalof Infectious Diseases vol 17 no 10 pp e802-e805 2013

[22] E Vichinsky L Neumayr S Trimble et al ldquoTransfusion com-plications in thalassemia patients a report from the Centers forDisease Control and Prevention (CME)rdquo Transfusion vol 54no 4 pp 972ndash981 2014

[23] S-C Wang K-H Lin J P S Chern et al ldquoSevere bacterialinfection in transfusion-dependent patients with thalassemiamajorrdquo Clinical Infectious Diseases vol 37 no 7 pp 984ndash9882003

[24] R Ahmed Kiani M Anwar U Waheed M J Asad S Abbasiand H Abbas Zaheer ldquoEpidemiology of transfusion transmit-ted infection among patients with 120573-thalassaemia major inPakistanrdquo Journal of Blood Transfusion vol 2016 Article ID8135649 5 pages 2016

[25] E Durante-Mangoni G Signoriello R Andini et al ldquoColistinand rifampicin compared with colistin alone for the treatmentof serious infections due to extensively drug-resistant Acine-tobacter baumannii a multicenter randomized clinical trialrdquoClinical Infectious Diseases vol 57 no 3 pp 349ndash358 2013

[26] N Filmann J Rey and S Schneeweiss ldquoPrevalence of anemiain inflammatory bowel diseases in European countries asystematic review and individual patient data meta-analysisrdquoInflammatory Bowel Diseases vol 20 no 5 pp 936ndash945 2014

[27] L C S Antunes F Imperi K J Towner and P Visca ldquoGenome-assisted identification of putative iron-utilization genes inAcinetobacter baumannii and their distribution among a geno-typically diverse collection of clinical isolatesrdquo Research inMicrobiology vol 162 no 3 pp 279ndash284 2011

[28] B L Mortensen and E P Skaar ldquoThe contribution of nutrientmetal acquisition and metabolism to Acinetobacter baumanniisurvival within the hostrdquo Frontiers in Cellular and InfectionMicrobiology vol 3 Article ID 00095 2013

[29] L De Leseleuc G Harris R KuoLee and W Chen ldquoIn vitroand in vivo biological activities of iron chelators and galliumnitrate against Acinetobacter baumanniirdquo Antimicrobial Agentsand Chemotherapy vol 56 no 10 pp 5397ndash5400 2012

Submit your manuscripts athttpswwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 201

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Molecular Biology International

GenomicsInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Signal TransductionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Evolutionary BiologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Genetics Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

Volume 2014

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Enzyme Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Microbiology

Page 4: ResearchArticle Acinetobacter baumannii Infection in ...downloads.hindawi.com/journals/bmri/2017/2351037.pdf · ResearchArticle Acinetobacter baumannii Infection in Transfusion Dependent

4 BioMed Research International

The true incidence of bacterial infections in transfusiondependent thalassemic patients has been neglected in thearea of clinical research In the present study 107 (1168)specimens showed growth of A baumannii out of total 916cultured blood specimens The results are aligned with thestudy of Wang et al [23] However the results of A bauman-nii infection in transfusion dependent thalassemic patientsremained unmatched as the present study is the first researchto report from Sindh region Regular transfusions mightlead to more complicated situations like iron overload if thepatients are not treated appropriately The transmission ofHCV HBV and HCV is a main issue in the developing coun-tries where the standards of blood safety are not really highIn accordance with the findings of the study conducted byAhmed Kiani et al [24] Transfusion Transmitted Infectionswere distressingly high andHCVwas observed as the leadingTTI along with the presence of HIV in some cases

Extensively drug resistant (XDR) Acinetobacter bauman-nii (Acb) might be the source of serious infections in censo-riously ill patients There is the only therapeutic option thatis colistin that often remains helpful Adding of rifampicinto colistin might be synergistic in vitro The study assessedthat the arrangement of rifampicin and colistin will condensethe mortality of XDR Acb infections as compared to colistinalone In serious XDR Acb infections 30-day mortality is notreduced by the addition of rifampicin to colistin The resultshighlighted that the rifampicin should not be regularly jointwith colistin in clinical practice The augmented rate of Acbannihilation with amalgamation treatment might still infer aclinical benefit [25]

When a potential threat is felt by the body Fe (iron) getstransferred to ferritin to be contained so that the injuriousand damaging invader cannot get to the iron Enough iron isobtained to make the red blood cells but there is no surplusremained to nourish the injurious pathogens A person withanemia will experience a modest decline depending on theunderlying causes of disease It will take place over timeobserving the onset of inflammation because of the presenceof disease or infectionThe values of hemoglobin will reach alow and normal range of 95ndash105 gdL and remain constantTherefore anemia of chronic disease can be recognized witha serum ferritin test [26]

As iron overload occurs in thalassemia patients becauseof regular blood transfusions particularly in those withoutiron chelating therapy there are more chances of gram-negative bacterial infectionsThepresence of iron predisposesthalassemic patients to bacterial infections [3] A baumanniisequesters iron by iron carriers and stores bound with hostrsquosproteins and thus it can combat decreased level of iron inblood [27]

It was found that A baumannii shows good ability tosequester hostrsquos iron as it produces large quantities of sid-erophores for Fe (III) transport [28] Keeping in mind thekey role of iron in Acinetobacter baumannii pathogenicity[28 29] iron chelator is considered as a nonantibiotic optionto combat certain bacterial infection As the transfusionsare dependent on thalassemia patients large quantities ofiron are observed therefore it can be said that it is an idealenvironment for the A baumannii growth [2 29]

5 Conclusion

The findings of A baumannii from the thalassemia patientsare supported by the previous studies as mentioned aboveIt is identified that iron overload is one of the risk factorsfor bacterial colonization Isolation of A baumannii fromthe thalassemia patients showed an alarming situation ofbacterial infections A continuous surveillance of transfusiondependent thalassemia patients is recommended for bacterialinfections Iron chelation therapy may alleviate the iron loadin thalassemia patients

Consent

A total of 916 patients were recruited into the study and allthe participants were provided with informed consent formsto ensure the confidentiality of the data collected from them

Conflicts of Interest

The authors declare that there are no conflicts of interestregarding the publication of this paper

Acknowledgments

The authors are very thankful to Mr Mohammad Ali Diag-nostic and Research Laboratory Liaquat University of Med-ical and Health Sciences (LUMHS) JamshoroHyderabadSindh Pakistan for his technical contribution to thisresearch Dr Saeed Sattar Shaik conceptualized the idea andgathered and compiled raw data Dr Muzaheed AbdulRasheed applied relevant statistical tools and analyzed andconcluded the data Dr Faisal Mousa Alzahrani interpretedthe data and wrote the manuscript All the authors read themanuscript and contributed intellectually

References

[1] KAAl-Anazi andAMAl-Jasser ldquoInfections caused byAcine-tobacter baumannii in recipients of hematopoietic stem celltransplantationrdquo Frontiers in Oncology vol 4 article 186 2014

[2] T Foley and A Simeonov ldquoTargeting iron assimilation todevelop new antibacterialsrdquo Expert Opinion on Drug Discoveryvol 7 no 9 pp 831ndash847 2012

[3] G Suleyman and G J Alangaden ldquoNosocomial fungal infec-tionsrdquo Infectious Disease Clinics of North America vol 30 no 4pp 1023ndash1052 2016

[4] D Grimaldi L Le Bourhis B Sauneuf et al ldquoSpecific MAITcell behaviour among innate-like T lymphocytes in critically illpatients with severe infectionsrdquo Intensive CareMedicine vol 40no 2 pp 192ndash201 2014

[5] L C S Antunes P Visca and K J Towner ldquoAcinetobacter bau-mannii evolution of a global pathogenrdquo Pathogens and Diseasevol 71 no 3 pp 292ndash301 2014

[6] V Russotto A Cortegiani G Graziano et al ldquoBloodstreaminfections in intensive care unit patients distribution andantibiotic resistance of bacteriardquo Infection and Drug Resistancevol 8 pp 287ndash296 2015

[7] V Russotto A Cortegiani S M Raineri and A GiarratanoldquoBacterial contamination of inanimate surfaces and equipment

BioMed Research International 5

in the intensive care unitrdquo Journal of Intensive Care vol 3 no 12015

[8] M Ramadan and M Mohamed Ismael Fouda ldquoRelationshipbetween elevated liver enzymes with iron overload and viralhepatitis in children withb-thalassemia majorrdquo Al-Azhar AssiutMedical Journal vol 13 no 2 2015

[9] J E Cassat and E P Skaar ldquoIron in infection and immunityrdquoCell Host and Microbe vol 13 no 5 pp 509ndash519 2013

[10] J L Kwiatkowski H-Y Kim A AThompson et al ldquoChelationuse and iron burden inNorthAmerican and British thalassemiapatients a report from the thalassemia longitudinal cohortrdquoBlood vol 119 no 12 pp 2746ndash2753 2012

[11] HAnsari Saqib S Tahir AMushtaq et al ldquoMolecular epidemi-ology of szlig-thalassemia in Pakistan far reaching implicationsrdquoIndian Journal of Human Genetics vol 2 no 4 pp 403ndash4082011

[12] M G Thompson B W Corey Y Si D W Craft and D VZurawski ldquoAntibacterial activities of iron chelators againstcommon nosocomial pathogensrdquo Antimicrobial Agents andChemotherapy vol 56 no 10 pp 5419ndash5421 2012

[13] M S Paksu A Karli S Paksu A K Guney S N Ozsevik andN Belet ldquoFatal sepsis in a child with thalassemia major due toSerratia marcescensrdquo Pediatrics International vol 56 no 5 pp796-797 2014

[14] S Shrestha ldquoIdentifying and assessing patientrsquos sepsis by nursesin an emergency department a literature reviewrdquo 2016

[15] P Gujja D R Rosing D J Tripodi and Y Shizukuda ldquoIronoverload cardiomyopathy better understanding of an increas-ing disorderrdquo Journal of the American College of Cardiology vol56 no 13 pp 1001ndash1012 2010

[16] D M Guerrero F Perez N G Conger et al ldquoAcinetobacterbaumannii-associated skin and soft tissue infections recogniz-ing a broadening spectrum of diseaserdquo Surgical Infections vol11 no 1 pp 49ndash57 2010

[17] S Akhlaghpoor A Ghahari A Morteza O Khalilzadeh AShakourirad and M R Alinaghizadeh ldquoQuantitative T2 mag-netic resonance imaging for evaluation of iron deposition in thebrain of 120573-thalassemia patientsrdquo Clinical Neuroradiology vol22 no 3 pp 211ndash217 2012

[18] S Talsania N Talsania and N Himanshu ldquoA cross sectionalstudy of thalassemia in Ahmedabad City Gujarat (hospitalbased)rdquo Healthline Journal of Indian Association of Preventiveand Social Medicine vol 2 no 1 pp 48ndash51 2011

[19] S Begum F Hasan S Hussain and A A Shah ldquoPrevalenceof multi drug resistant Acinetobacter baumannii in the clinicalsamples from tertiary care hospital in Islamabad PakistanrdquoPakistan Journal ofMedical Sciences vol 29 no 5 pp 1253ndash12582013

[20] M J McConnell L Actis and J Pachon ldquoAcinetobacter bau-mannii human infections factors contributing to pathogenesisand animal modelsrdquo FEMS Microbiology Reviews vol 37 no 2pp 130ndash155 2013

[21] M Eveillard M Kempf O Belmonte H Pailhories andM-L Joly-Guillou ldquoReservoirs of Acinetobacter baumanniioutside the hospital and potential involvement in emerginghuman community-acquired infectionsrdquo International Journalof Infectious Diseases vol 17 no 10 pp e802-e805 2013

[22] E Vichinsky L Neumayr S Trimble et al ldquoTransfusion com-plications in thalassemia patients a report from the Centers forDisease Control and Prevention (CME)rdquo Transfusion vol 54no 4 pp 972ndash981 2014

[23] S-C Wang K-H Lin J P S Chern et al ldquoSevere bacterialinfection in transfusion-dependent patients with thalassemiamajorrdquo Clinical Infectious Diseases vol 37 no 7 pp 984ndash9882003

[24] R Ahmed Kiani M Anwar U Waheed M J Asad S Abbasiand H Abbas Zaheer ldquoEpidemiology of transfusion transmit-ted infection among patients with 120573-thalassaemia major inPakistanrdquo Journal of Blood Transfusion vol 2016 Article ID8135649 5 pages 2016

[25] E Durante-Mangoni G Signoriello R Andini et al ldquoColistinand rifampicin compared with colistin alone for the treatmentof serious infections due to extensively drug-resistant Acine-tobacter baumannii a multicenter randomized clinical trialrdquoClinical Infectious Diseases vol 57 no 3 pp 349ndash358 2013

[26] N Filmann J Rey and S Schneeweiss ldquoPrevalence of anemiain inflammatory bowel diseases in European countries asystematic review and individual patient data meta-analysisrdquoInflammatory Bowel Diseases vol 20 no 5 pp 936ndash945 2014

[27] L C S Antunes F Imperi K J Towner and P Visca ldquoGenome-assisted identification of putative iron-utilization genes inAcinetobacter baumannii and their distribution among a geno-typically diverse collection of clinical isolatesrdquo Research inMicrobiology vol 162 no 3 pp 279ndash284 2011

[28] B L Mortensen and E P Skaar ldquoThe contribution of nutrientmetal acquisition and metabolism to Acinetobacter baumanniisurvival within the hostrdquo Frontiers in Cellular and InfectionMicrobiology vol 3 Article ID 00095 2013

[29] L De Leseleuc G Harris R KuoLee and W Chen ldquoIn vitroand in vivo biological activities of iron chelators and galliumnitrate against Acinetobacter baumanniirdquo Antimicrobial Agentsand Chemotherapy vol 56 no 10 pp 5397ndash5400 2012

Submit your manuscripts athttpswwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 201

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Molecular Biology International

GenomicsInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Signal TransductionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Evolutionary BiologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Genetics Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

Volume 2014

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Enzyme Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Microbiology

Page 5: ResearchArticle Acinetobacter baumannii Infection in ...downloads.hindawi.com/journals/bmri/2017/2351037.pdf · ResearchArticle Acinetobacter baumannii Infection in Transfusion Dependent

BioMed Research International 5

in the intensive care unitrdquo Journal of Intensive Care vol 3 no 12015

[8] M Ramadan and M Mohamed Ismael Fouda ldquoRelationshipbetween elevated liver enzymes with iron overload and viralhepatitis in children withb-thalassemia majorrdquo Al-Azhar AssiutMedical Journal vol 13 no 2 2015

[9] J E Cassat and E P Skaar ldquoIron in infection and immunityrdquoCell Host and Microbe vol 13 no 5 pp 509ndash519 2013

[10] J L Kwiatkowski H-Y Kim A AThompson et al ldquoChelationuse and iron burden inNorthAmerican and British thalassemiapatients a report from the thalassemia longitudinal cohortrdquoBlood vol 119 no 12 pp 2746ndash2753 2012

[11] HAnsari Saqib S Tahir AMushtaq et al ldquoMolecular epidemi-ology of szlig-thalassemia in Pakistan far reaching implicationsrdquoIndian Journal of Human Genetics vol 2 no 4 pp 403ndash4082011

[12] M G Thompson B W Corey Y Si D W Craft and D VZurawski ldquoAntibacterial activities of iron chelators againstcommon nosocomial pathogensrdquo Antimicrobial Agents andChemotherapy vol 56 no 10 pp 5419ndash5421 2012

[13] M S Paksu A Karli S Paksu A K Guney S N Ozsevik andN Belet ldquoFatal sepsis in a child with thalassemia major due toSerratia marcescensrdquo Pediatrics International vol 56 no 5 pp796-797 2014

[14] S Shrestha ldquoIdentifying and assessing patientrsquos sepsis by nursesin an emergency department a literature reviewrdquo 2016

[15] P Gujja D R Rosing D J Tripodi and Y Shizukuda ldquoIronoverload cardiomyopathy better understanding of an increas-ing disorderrdquo Journal of the American College of Cardiology vol56 no 13 pp 1001ndash1012 2010

[16] D M Guerrero F Perez N G Conger et al ldquoAcinetobacterbaumannii-associated skin and soft tissue infections recogniz-ing a broadening spectrum of diseaserdquo Surgical Infections vol11 no 1 pp 49ndash57 2010

[17] S Akhlaghpoor A Ghahari A Morteza O Khalilzadeh AShakourirad and M R Alinaghizadeh ldquoQuantitative T2 mag-netic resonance imaging for evaluation of iron deposition in thebrain of 120573-thalassemia patientsrdquo Clinical Neuroradiology vol22 no 3 pp 211ndash217 2012

[18] S Talsania N Talsania and N Himanshu ldquoA cross sectionalstudy of thalassemia in Ahmedabad City Gujarat (hospitalbased)rdquo Healthline Journal of Indian Association of Preventiveand Social Medicine vol 2 no 1 pp 48ndash51 2011

[19] S Begum F Hasan S Hussain and A A Shah ldquoPrevalenceof multi drug resistant Acinetobacter baumannii in the clinicalsamples from tertiary care hospital in Islamabad PakistanrdquoPakistan Journal ofMedical Sciences vol 29 no 5 pp 1253ndash12582013

[20] M J McConnell L Actis and J Pachon ldquoAcinetobacter bau-mannii human infections factors contributing to pathogenesisand animal modelsrdquo FEMS Microbiology Reviews vol 37 no 2pp 130ndash155 2013

[21] M Eveillard M Kempf O Belmonte H Pailhories andM-L Joly-Guillou ldquoReservoirs of Acinetobacter baumanniioutside the hospital and potential involvement in emerginghuman community-acquired infectionsrdquo International Journalof Infectious Diseases vol 17 no 10 pp e802-e805 2013

[22] E Vichinsky L Neumayr S Trimble et al ldquoTransfusion com-plications in thalassemia patients a report from the Centers forDisease Control and Prevention (CME)rdquo Transfusion vol 54no 4 pp 972ndash981 2014

[23] S-C Wang K-H Lin J P S Chern et al ldquoSevere bacterialinfection in transfusion-dependent patients with thalassemiamajorrdquo Clinical Infectious Diseases vol 37 no 7 pp 984ndash9882003

[24] R Ahmed Kiani M Anwar U Waheed M J Asad S Abbasiand H Abbas Zaheer ldquoEpidemiology of transfusion transmit-ted infection among patients with 120573-thalassaemia major inPakistanrdquo Journal of Blood Transfusion vol 2016 Article ID8135649 5 pages 2016

[25] E Durante-Mangoni G Signoriello R Andini et al ldquoColistinand rifampicin compared with colistin alone for the treatmentof serious infections due to extensively drug-resistant Acine-tobacter baumannii a multicenter randomized clinical trialrdquoClinical Infectious Diseases vol 57 no 3 pp 349ndash358 2013

[26] N Filmann J Rey and S Schneeweiss ldquoPrevalence of anemiain inflammatory bowel diseases in European countries asystematic review and individual patient data meta-analysisrdquoInflammatory Bowel Diseases vol 20 no 5 pp 936ndash945 2014

[27] L C S Antunes F Imperi K J Towner and P Visca ldquoGenome-assisted identification of putative iron-utilization genes inAcinetobacter baumannii and their distribution among a geno-typically diverse collection of clinical isolatesrdquo Research inMicrobiology vol 162 no 3 pp 279ndash284 2011

[28] B L Mortensen and E P Skaar ldquoThe contribution of nutrientmetal acquisition and metabolism to Acinetobacter baumanniisurvival within the hostrdquo Frontiers in Cellular and InfectionMicrobiology vol 3 Article ID 00095 2013

[29] L De Leseleuc G Harris R KuoLee and W Chen ldquoIn vitroand in vivo biological activities of iron chelators and galliumnitrate against Acinetobacter baumanniirdquo Antimicrobial Agentsand Chemotherapy vol 56 no 10 pp 5397ndash5400 2012

Submit your manuscripts athttpswwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 201

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Molecular Biology International

GenomicsInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Signal TransductionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Evolutionary BiologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Genetics Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

Volume 2014

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Enzyme Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Microbiology

Page 6: ResearchArticle Acinetobacter baumannii Infection in ...downloads.hindawi.com/journals/bmri/2017/2351037.pdf · ResearchArticle Acinetobacter baumannii Infection in Transfusion Dependent

Submit your manuscripts athttpswwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 201

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Molecular Biology International

GenomicsInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Signal TransductionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Evolutionary BiologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Genetics Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

Volume 2014

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Enzyme Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Microbiology