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  Table of Contents    
CASE REPORT  
Year : 2011  |  Volume : 54  |  Issue : 1  |  Page : 180-182
Fulminating septicemia due to persistent pan-resistant community-acquired metallo-β-lactamase (IMP-1)-positive Acinetobacter baumannii


1 Department of Microbiology, King Edward Memorial Hospital, Interdisciplinary School of Biomedical Sciences, University of Pune Affiliate, Pune, India
2 DNA Sequencing Laboratory, Agharkar Research Institute, Pune, India
3 College of Medicine, Drexel University, Philadelphia, PA 19102, USA

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Date of Web Publication7-Mar-2011
 

   Abstract 

Acinetobacter baumannii is considered as an emerging nosocomial pathogen and is renowned for its multi-drug resistance. We report a case of community-acquired pan-resistant A. baumannii caused fulminating septicemia. The treatment failure led to death. The A. baumannii strain isolated from blood, pus, urine and tracheal aspirate was confirmed by 16S r-RNA sequence homology and found positive for metallo-β-lactamase IMP-1, and was found to be a strong biofilm producer. The isolate was only susceptible (moderately) to colistin.

Keywords: Acinetobacter baumannii , carbapenemase extended spectrum β lactamase, IMP, metallo-β-lactamase, nosocomial infection, pan-resistant, septicemia

How to cite this article:
Telang NV, Satpute MG, Dhakephalkar PK, Niphadkar KB, Joshi SG. Fulminating septicemia due to persistent pan-resistant community-acquired metallo-β-lactamase (IMP-1)-positive Acinetobacter baumannii. Indian J Pathol Microbiol 2011;54:180-2

How to cite this URL:
Telang NV, Satpute MG, Dhakephalkar PK, Niphadkar KB, Joshi SG. Fulminating septicemia due to persistent pan-resistant community-acquired metallo-β-lactamase (IMP-1)-positive Acinetobacter baumannii. Indian J Pathol Microbiol [serial online] 2011 [cited 2019 Nov 15];54:180-2. Available from: http://www.ijpmonline.org/text.asp?2011/54/1/180/77397



   Introduction Top


Acinetobacter baumannii , the gram-negative coccobacillus, is ubiquitous in nature. This organism can survive for months together on inanimate surfaces as well as on human skin and mucous membranes, making nosocomial transmission extremely difficult to prevent. [1] It has emerged as the third most common nosocomial pathogen among gram-negative organisms, responsible for serious infections and nosocomial outbreaks. It affects particularly the patients who are critically ill or/and have underlying debilitating diseases. It can cause significant heath problems in the elderly, with high rates of mortality due to severe and fatal infection involving the respiratory tract, the urinary tract, and wounds and bacteremia (including catheter-associated blood stream infection). The risk factors usually constitute underlying diseases, intravascular catheterization, mechanical ventilation, old age, prior treatment with broad-spectrum antibiotics or steroids (including immunocompromised status), prolonged hospitalization, and stay in the intensive care unit (ICU). A. baumannii has an intrinsic propensity to acquire multiple drug resistant genes; and whole-genome sequencing of resistant strain has proven this. [2] In addition, liberal use of carbapenems and third-generation cephalosporins appears to be related to the development of multi-drug resistant phenotypes, which helps in turning them into pan-resistant. Such phenotypes are known to harbor extended-spectrum β-lactamase(s) (ESBLs) and metallo-β-lactamases (MBLs). [2],[3]


   Case Report Top


A 63-year-old lady was admitted to the hospital because of giddiness, palpitation, chest discomfort, shortness of breath, blackout of vision, hypertension, and hyperthyroidism. Her echocardiogram showed atrial fibrillation with fast ventricular rate. On admission, she had fever with a temperature of 102°F and was drowsy, and her hemoglobin was 10.1 g%, white blood cell count was 27,000/mm 3 , and platelet count was 133,000/mm 3 . Because of her poor general condition, the patient was transferred to ICU for further management. She was intubated and blood was collected for culture and sensitivity, on admission. She had fever spikes; and during that period, she received piperacillin with tazobactam and ceftriaxone as an empirical treatment. Blood taken upon admission had shown gram-negative coccobacilli, which could not be confirmed in about 4 days. Meanwhile, as the patient was symptomatically well, the empirical therapy was discontinued after 8 days. Low grade fever continued for 15 days.

The peripheral catheter was removed (which was in place for 8 days); and hemodialysis was begun because of worsened renal insufficiency. Two consecutive blood cultures were processed which were collected in the second week of therapy, which again yielded gram-negative coccobacilli and were identified as A. baumannii by both the conventional methods and automated VITEK 2 system (Bio Merieux, Craponne, France). During this period, the patient developed bedsores with discharge. Bedsore swab (pus) was examined for culture and A. baumannii and Pseudomonas aeruginosa were isolated. Urine routine examination revealed proteins and plenty of pus cells, so urine culture was sent for testing. A. baumannii and Candida tropicalis were isolated from the urine sample. Antibiotic sensitivity was verified by disk diffusion method as well as on automated VITEK 2 system. Antibiogram showed resistance to all major groups, viz., carbapenems, aminoglycosides, cephalosporins, penicillins, and fluoroquinolones, and moderate sensitivity to colistin. Colistin and amphoterecin-B (antifungal) were immediately started as treatment, and later imipenem + cilastatin was added. Meanwhile, the patient developed endotracheal bleeding. Her tracheal aspirate was sent for culture. Culture yielded A. baumannii. Sensitivity pattern of A. baumannii was indistinguishable for all samples (blood, pus, urine, tracheal aspirate). After being hospitalized for 36 days, the patient expired due to severe septicemia.

A. baumannii was found positive for ESBL and MBL when tested by standard double disk synergy, and test using imipenem and ethylenediaminetetraacetic acid (EDTA). All isolates were confirmed as A. baumannii by 16S rRNA technology using partial sequence homology, using ABI PRISM 3100 genetic sequencing system (Applied Biosystems, Foster City, USA) as described. [4] The isolates were found to be strong biofilm producers when tested by microtiter plate assay. [5] Broth alone and known biofilm-positive strain of A. baumannii (ATCC 19606) were included as negative and positive controls, respectively. The isolates were processed for the molecular confirmation of MBL and ESBL, using the described methods and primers. [6],[7] The primer pairs of IMP-1, IMP-2, VIM-1, VIM-2, and SPM-1 were tested for confirmation of MBL. The analysis of polymerase chain reaction (PCR) sequencing confirmed the presence bla(IMP-1) gene. Past history of patient did not reveal much information. She was referred from a peripheral village health center. She was a known case of hypertension and hyperthyroidism, but no information could be obtained about her prior hospitalization and antimicrobial treatment which can be correlated.


   Discussion Top


In the present case, the initial presentation is indicative of moderate sepsis. It is more likely that the patient got infected before hospitalization, as the first blood culture upon admission was positive for the growth, which was eventually identified as of A. baumannii and moderate to severe leukocytosis was noted. We assume that the intense empiric therapy might have transiently suppressed the infection, which got erupted after 8 days. Apparently, it looks like throughout the course of therapies (all three treatment regimes), A. baumannii was present in the blood. In addition, it was subsequently recovered from the wound fluid, urine, and bronchial aspirates. All A. baumannii isolates had shown similar phenotypic and genotypic features and indistinguishable antibiograms. The antibiotic susceptibility patterns clearly suggested that the isolates were pan-drug resistant. The prominent risk factors in this case, such as ICU stay, intravenous catheterization, and hemodialysis, can be ruled out and thus community-acquired (CA) A. baumannii infection is favored more. Although past history of prior hospitalization within 6 months and antibiotic treatment could not be tracked, there is a still a possibility. This patient was never admitted to our hospital before and was referred by a peripheral clinic.

Although rare, CA infection has been reported on occasions. [8] To our knowledge, there is no published report on CA-pan-drug resistant A. baumannii infection that caused generalized septicemia, multi-organ involvement, and death due to septic shock. The isolate did not show susceptibility to any of the common anti-acinetobacter agents. Polymyxins (colistin and polymyxin-B) have saved the lives of severely infected patients and have been increasingly used as a last resort in fulminating infections due to multidrug resistant (MDR) A. baumannii. [9] In the present patient, colistin did not help, and led to treatment failure. MDR A. baumannii represents the strain resistant to three or more classes of antibacterials. Current literature suggests that the presence of carbapenemase(s) itself may be sufficient to define A. baumannii as highly resistant, and successful combined therapy of colistin and rifampicin is promising and synergistic in clinical setting. [10] Rifampicin and colistin was not a standard regime in our hospital at that time, and only recently has been implemented. Colistin with imipenem + cilastatin therapy failed in this patient. Carbapenemases (such as MBLs) are reported with increasing frequencies from several countries worldwide, and the strains often exhibit pan-resistant phenotypes. [3] During molecular analysis, chromosomal DNA revealed the presence of IMP-1 gene in all these isolates. No plasmid was detected during analysis. Although rare, chromosome-borne IMP-1 has been reported from other gram-negative pathogens, but to our knowledge it has not been reported from A. baumannii so far. The phenotypes which carry IMP genes are known to exhibit resistance against many non-β-lactam agents, in addition to routine β-lactams and carbapenems. [11] All of these together explain a horrific molecular situation, making the phenotype highly multi-drug resistant. Such types of phenotype are rarely reported and often prove fatal. In this case, it was the cause of severe septicemia and led to multisystem failure and death of the patient. Plasmid-borne IMP-1 was reported from Taiwan and lateral gene transfer as a mode of dissemination was established. [11] Thus, MBL genes can be present on both the plasmid or/and chromosome in Acinetobacter, carrying risk of dissemination of pan-resistant phenotypes. A. baumannii is an excellent human colonizer, colonizing population from both the community and healthcare center. Isolate from the present patient was found to be strong biofilm-positive. MDR A. baumannii phenotypes show a positive relationship with biofilm formation, suggesting linkage of these virulence factors and are excellent colonizers. [12]

Many virulence factors conferring antibiotic resistance have been linked to MDR status of this organism, which were thought to contribute to its pathogenicity. Antibiotic resistant-unrelated pathogenicity and associated virulence factors are largely unknown and need further research. At the same time, it is reported that A. baumannii devotes a considerable portion of this genome to pathogenicity and virulence islands. [8],[9] Does this mean that A. baumannii, a well-known nosocomial player, is turning a CA candidate pathogen? Or community serves as a potential reservoir of it? In the present case, no underlying chronic disease or ailment was found which can be linked to predisposition, and the patient had sepsis/toxemia like presentation at the time of admission, involving multiple body systems. Therefore, the possibility of CA of infection is more likely. A moderate prevalence of MDR A. baumannii is seen these days in our hospital since this incidence. But further systemic analysis will be required for correlation of their genetic relatedness. The clinicians should be aware that MDR A. baumannii like organism can trigger a novel clinical course with remarkable virulence, and there could not be any therapeutic option open in due course.

 
   References Top

1.Bergogne-Berezin E, Towner KJ. Acinetobacter spp. as nosocomial pathogens: Microbiological, clinical and epidemiology features. Clin Microbiol Rev 1996;9:148-65.   Back to cited text no. 1
    
2.Joshi SG, Litake GM, Niphadkar KB, Ghole VS. Multidrug resistant Acinetobacter baumannii isolates from a teaching hospital. J Infect Chemother 2003;9:187-90.   Back to cited text no. 2
    
3.Maltezou HC. Metallo-beta-lactamases in Gram-negative bacteria: Introducing the era of pan-resistant? Int J Antimicrob Agents 2009;33:405-7.   Back to cited text no. 3
    
4.Ercolini D, Russo F, Nasi A, Ferranti P, Villani F. Mesophilic and psychrotrophic bacteria from meat and their spoilage potential in vitro and in beef. Appl Environ Microbiol 2009;75:1990-2001.   Back to cited text no. 4
    
5.Burmolle M, Webb JS, Rao D, Hansen LH, Sorensen SL, Kjelleberg S. Enhanced biofilm formation and increased resistance to antimicrobial agents and bacterial invasion are caused by synergistic interaction in multispecies biofilms. Appl Environ Microbiol 2006;72:3916-23.   Back to cited text no. 5
    
6.Yan JJ, Hsueh PR, Ko WC, Luh KT, Tsai SH, Wu HM, Wu, JJ. Metallo-â-lactamases in clinical Pseudomonas isolates in Taiwan and identification of VIM-3, a novel variant of the VIM-2 enzyme. Antimicrob Agents Chemother 2001;45:2224-8.   Back to cited text no. 6
    
7.Woodford N, Zhang J, Kaufmann ME, Yarde S, Tomas MM, Faris C, et al. Detection of Pseudomonas aeruginosa isolates producing VEB-type extended-spectrum â-lactamases in the United Kingdom. J Antimicrob Chemother 2008;62:1265-8.   Back to cited text no. 7
    
8.Lowman W, Kalk T, Menezes CN, John MA, Grobusch MP. A case of community-acquired Acinetobacter baumannii meningitis - has the threat moved beyond the hospital? J Med Microbiol 2008;57:676-8.   Back to cited text no. 8
    
9.Charnot-Katsikas A, Dorafshar AH, Aycock JK, David MZ, Weber SG, Frank KM. Two cases of necrotizing fasciitis due to Acinetobacter baumannii. J Clin Microbiol 2009;47:258-63.   Back to cited text no. 9
    
10.Poirel L, Nordmann P. Carbapenem resistance in Acinetobacter baumannii: Mechanisms and epidemiology. Clin Microbiol Infect 2006;12:826-36.   Back to cited text no. 10
    
11.Liu SY, Lin JY, Chu C, Su LH, Lin TY, Chiu CH. Integron-associated imipenem resistance in Acinetobacter baumannii isolated from a regional hospital in Taiwan. Int J Antimicrob Agents 2006;27:81-4.   Back to cited text no. 11
    
12.Rao RS, Karthika RU, Singh SP, Shashikala P, Kanungo R, Jayachandran S, et al. Correlation between biofilm production and multiple drug resistance in imipenem resistant clinical isolates of Acinetobacter baumannii. Indian J Med Microbiol 2008;26:333-7.  Back to cited text no. 12
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Correspondence Address:
Suresh G Joshi
245 N 15th St, Drexel University, College of Medicine, Philadelphia, PA 19102
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DOI: 10.4103/0377-4929.77397

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