|Year : 2017 | Volume
| Issue : 3 | Page : 180-184
Pseudomonas aeruginosa and its sensitivity spectrum in chronic suppurative otitis media: A study from Garhwal hills of Uttarakhand State, India
Deepak Juyal1, Munesh Sharma2, Vikrant Negi2, Rajat Prakash1, Neelam Sharma2
1 Department of Microbiology, All Institute of Medical Sciences, New Delhi, India
2 Department of Microbiology, Veer Chandra Singh Garhwali Government Medical Sciences and Research Institute, Srikot, Srinagar Garhwal, Uttarakhand, India
|Date of Web Publication||31-Aug-2017|
Department of Microbiology, All India Institute of Medical Sciences, New Delhi - 110 019
Source of Support: None, Conflict of Interest: None
Introduction: Chronic suppurative otitis media (CSOM) is a chronic inflammation of the middle ear and mastoid cavity, with recurrent ear discharge through a perforated tympanic membrane. It is a major health problem in developing countries causing serious local damage and life-threatening complications. The advent of sophisticated systemic antibiotics and their irrational use has led to the emergence of multidrug-resistant (MDR) bacterial strains and disease complication in return. Pseudomonas aeruginosa, one of the most common organisms to cause CSOM, is a notorious pathogen and is known for its MDR attribute. Objective: The aim of this study was to know the prevalence of P. aeruginosa among the patients suffering from CSOM, to analyze their antimicrobial susceptibility pattern, and to find out MDR P. aeruginosa strains. Materials and Methods: A total of 571 patients clinically diagnosed of CSOM were enrolled in the study (559 patients with unilateral and 12 with bilateral discharge), and 583 samples were obtained from them. Sample processing and identification was done by standard bacteriological methods. One hundred eighty-seven strains were identified as P. aeruginosa and were subjected to antimicrobial susceptibility testing for 10 different antibiotics categorized into five classes. Results: Of total 583 samples collected, growth was seen in 576 (98.8%) samples. P. aeruginosa strains were isolated from 187 (32.1%) samples. Piperacillin-tazobactam (75.4%), amikacin (74.3%), imipenem (70.6%), and cefepime (69.0%) were found to be the most effective antibiotics. Twenty-nine (15.5%) strains were resistant to all the five classes of antibiotics tested. The rate of resistance to fluoroquinolones (48.7%) was highest, followed by antipseudomonal penicillin (41.7%), and was lowest for carbapenems (29.4%). Conclusion: Knowing the etiological agents of CSOM and their antibiogram is of paramount importance for an efficient treatment and prevention of both disease complications and antimicrobial resistance.
Keywords: Aminoglycosides, chronic suppurative otitis media, fluoroquinolones, multidrug resistance, Pseudomonas aeruginosa
|How to cite this article:|
Juyal D, Sharma M, Negi V, Prakash R, Sharma N. Pseudomonas aeruginosa and its sensitivity spectrum in chronic suppurative otitis media: A study from Garhwal hills of Uttarakhand State, India. Indian J Otol 2017;23:180-4
|How to cite this URL:|
Juyal D, Sharma M, Negi V, Prakash R, Sharma N. Pseudomonas aeruginosa and its sensitivity spectrum in chronic suppurative otitis media: A study from Garhwal hills of Uttarakhand State, India. Indian J Otol [serial online] 2017 [cited 2021 Apr 13];23:180-4. Available from: https://www.indianjotol.org/text.asp?2017/23/3/180/213866
| Introduction|| |
Chronic suppurative otitis media (CSOM), also called as chronic active mucosal otitis media, chronic otomastoiditis, and chronic tympanomastoiditis, is a chronic inflammation of the middle ear and mastoid cavity, which presents with recurrent ear discharge or otorrhea through a perforated tympanic membrane (TM). CSOM is usually classified into two types, tubotympanic and atticoantral depending on whether the disease process affects the pars tensa or pars flaccida of the TM. Tubotympanic is called as a safe or benign type as there is no serious complication whereas atticoantral is called as the unsafe or dangerous type because of associated complication and may be life-threatening at times. Incidence of the disease is higher in developing countries, especially among low socioeconomic societies because of malnutrition, overcrowding, poor hygiene, inadequate health care, and recurrent upper respiratory tract infections. CSOM is a persistent disease with high risk of irreversible complications which may range from persistent otorrhea, mastoiditis, labyrinthitis, and facial palsy to more serious intracranial abscesses or thromboses., While the incidence of such complications is low, they need to be borne in mind when faced by a patient with active CSOM. The most important symptoms which make patients seek medical advice are hearing loss and suppurative drainage, reported in around 50% of the cases. Early diagnosis of etiological agent ensures prompt and effective treatment to avoid such complications.
CSOM, whether atticoantral or tubotympanic disease, is almost always associated with mixed bacterial flora. Various studies have shown both Gram-positive and Gram-negative organisms responsible for CSOM.,, The most common microorganisms found in CSOM are Pseudomonas aeruginosa, Staphylococcus aureus, Proteus mirabilis, diphtheroid group, and anaerobic bacteria.,, Changes in bacterial flora of CSOM in the last decade have been confirmed and described by many authors.,,, Topical preparations containing antibiotics and steroids, to reduce otorrhea and to provide local anti-inflammatory effect, are the mainstays of medical management of CSOM; however, issues such as bacterial resistance and ototoxicity with both topical and systemic antibiotics are the matter of concern. Irrational use of antibiotics has led to the emergence of multidrug-resistant (MDR) strains and disease complication in return, thereby making the management of CSOM more difficult. In developing countries, this problem is rapidly increasing and the important factors associated were found to be indiscriminate use of antibiotics, overcrowding, poor hospital hygiene, and lack of resources and personnel trained in infection control.
P. aeruginosa is one of the most predominant organisms to cause CSOM,, with an incidence ranging from 21% to 52.94%. It is a notorious pathogen to cause nosocomial infections and is known for its MDR attribute. Hence, the periodic update of prevalence, antibiogram of the etiological agents for CSOM, and the MDR strains involved would be helpful in therapy and management of patients.
This study was undertaken to know the prevalence of P. aeruginosa among the patients suffering from CSOM, to analyze the antimicrobial susceptibility patterns of these strains to commonly prescribed antimicrobials, and to find out the MDR P. aeruginosa (MDRPA) strains.
| Materials and Methods|| |
This cross-sectional study was carried out in the Department of Microbiology of our hospital, a tertiary care center in Uttarakhand, India, from January 2012 to December 2012. With the Institutional Ethics Committee approval and individual informed consent (signed by patient or parent/guardian), samples were obtained from the patients clinically diagnosed of CSOM. A total of 583 samples were collected from 571 patients (559 patients with unilateral discharge comprising 559 samples and 12 with bilateral discharge comprising 24 samples). One hundred eighty-seven strains of P. aeruginosa were obtained from 184 patients (181 with unilateral and 3 with bilateral discharge).
Inclusion and exclusion criteria
All the patients having discharge from one or both the ears for >3 months with TM perforation were included in the study. Patients with discharge of <3 months, discharge with intact TM (otitis externa), and who were on antibiotics (topical/oral/systemic) for last 7 days were excluded from the study.
Sample collection and processing
The external auditory canal (EAC) of each patient was cleaned well with alcohol (70% isopropanol), and the aural discharge was collected using sterile cotton swabs (HiMedia Laboratories Pvt. Ltd, Mumbai, India). Utmost care was taken to avoid any contact with the EAC. The specimens collected were transported immediately to microbiology laboratory for further processing. The swabs were inoculated on sterile blood agar, chocolate agar, and MacConkey's agar plates and were then incubated at 37°C for 24–48 h. Emergent bacterial colonies were identified according to the standard bacteriological methods.,
Antimicrobial susceptibility testing
Antibiotic sensitivity tests were carried out according to the Clinical Laboratory Standards Institute (CLSI) guidelines. A total of 187 isolates of P. aeruginosa were tested for their sensitivity to amikacin (AMK, 30 μg), gentamicin (GM, 10 μg), tobramycin (TOB, 10 μg), ceftazidime (CAZ, 30 μg), cefepime (CFP, 50 μg), piperacillin (PIP, 100 μg), PIP/tazobactam (PTZ, 100/10 μg), imipenem (IMP, 10 μg), ciprofloxacin (CIP, 5 μg), and levofloxacin (LFX, 5 μg) by modified Kirby-Bauer disc diffusion method using Mueller-Hinton agar (MHA) medium. A suspension of the isolated colonies of each test strain equivalent to a 0.5 McFarland's standard was prepared in sterile normal saline. Briefly, a suspension of each strain was made so that the turbidity was equal to 0.5 McFarland standards and then plated as a lawn culture onto MHA. Antibiotic discs were placed and plates were incubated at 37°C for 18–24 h. Results were interpreted in accordance with CLSI guidelines. Escherichia More Details coli ATCC 25922 and P. aeruginosa ATCC 27853 were used as control strains.
There is no clear and official definition of MDR. In general, however, resistance to >3 core antibiotics (AMK and/or GM, CAZ, CIP, IMP, PIP) is classified as MDR. In the present study, MDRPA was defined as a strain resistant to at least three of the five core antibiotics (AMK, CAZ, PIP, CIP, and IMP).
Ten antibiotics were categorized into five classes – aminoglycosides (AMK, GM, and TOB), cephalosporins (CAZ and CFP), antipseudomonal penicillins (PIP and PTZ), carbapenems (IMP), and fluoroquinolones (CIP and LFX) and defined MDR as resistance to at least three of these five classes. In designations of MDR, resistance to at least one individual antibiotic in each class was defined as resistance to that entire class.
All dehydrated media, reagents, sterile swabs, and antibiotic discs were procured from HiMedia Laboratories Pvt. Ltd., Mumbai, India.
| Results|| |
From the total of 583 samples, growth was seen in 576 with a total positivity rate of 98.8%. The most predominant bacterial agent found in chronic discharging ears was P. aeruginosa (32.1%, 187/583) followed by S. aureus (29.3%, 171/583) and Klebsiella spp. (17.32%, 101/583). [Table 1] depicts the distribution of various bacterial isolates in CSOM samples.
|Table 1: Different types of organisms isolated from chronic suppurative otitis media patients|
Click here to view
A total of 187 strains of P. aeruginosa were obtained from 184 patients (181 with unilateral and 3 with bilateral discharge) with male: female ratio of 1.3:1 (males - 103, females - 81). The mean age of these patients was 27 years.
All 187 strains were subjected to antimicrobial susceptibility testing, and the results of the same are shown in [Table 2]. PTZ (75.4%, 141/187) and AMK (74.3%, 139/187) were found to be the most effective antibiotics followed by IMP (70.6%, 132/187) and CFP (69.0%, 129/187). High degree of resistance was seen for CIP (48.7%, 91/187), LFX (45.5%, 85/187), and PIP (41.7%, 78/187) followed by GM (38%, 71/187), TOB (35.3%, 66/187), and CAZ (34.8%, 65/187).
|Table 2: Shows isolation rate of Pseudomonas aeruginosa strains susceptible and resistant to each antibiotic class (n=187)|
Click here to view
The majority of P. aeruginosa strains were susceptible to all the five classes (49.2%, 92/187) of antibiotics tested. Almost 22.5% (42/187) strains were resistant to three classes and 9.1% (17/187) to four classes, whereas 15.5% (29/187) strains were resistant to all the five classes of antibiotics. The rate of resistance to fluoroquinolones was highest (48.7%, 91/187) followed by antipseudomonal penicillin (41.7%, 78/187), aminoglycosides (38.0%, 71/187), and cephalosporins (34.8%, 65/187). Lowest degree of resistance was seen for carbapenems (29.41%, 55/187).
On the basis of antibiotic sensitivity testing (AST) results, 88 isolates were designated as MDR strains.
| Discussion|| |
P. aeruginosa, a well-known pathogen, is a causative agent for various diseases ranging from minor skin infections to fulminant septicemia. It is the predominant cause of CSOM in tropical region and does not usually inhabit the upper respiratory tract. Its presence in the middle ear cannot be ascribed to an invasion through Eustachian tube More Details (ET), and it should be considered as a secondary invader gaining access to the middle ear through defect in TM. Poor hygiene and unorthodox approach to treatment like use of unconventional ear drops and concoctions such as oil and honey into the middle ear may also contribute to its presence in middle ear.
Results of the present study showed P. aeruginosa (32.07%) as the most common organism from active CSOM infections followed by S. aureus (29.33%). This is in tandem with the observations made by many other authors.,,,,, In contrast, many researchers have reported S. aureus as the predominant causative agent for CSOM followed by P. aeruginosa.,, Moreover, this could be due to the geographical variations and the different group of population studied. The increased isolation rate of P. aeruginosa has its own implications, as this organism is an important cause of nosocomial infections. P. aeruginosa is a bacterial species that is difficult to treat as it does not have particular environmental or nutritional requirements to grow and is highly resistant to conventional antibiotics.P. aeruginosa can thrive well in the ear environment, is difficult to eradicate, and has been particularly implicated in the causation of bony necrosis and mucosal disease. It has been proposed that P. aeruginosa evades the host defense mechanism by taking advantage of a shell of surrounding damaged epithelium that causes decreased blood circulation to the area. The organism then damages the tissues, interferes with normal body defenses and by virtue of various enzymes and toxins inactivates the antibiotics.
Although inherently resistant to several antibiotics, P. aeruginosa was originally sensitive to the antipseudomonal beta-lactam (BL) class antibiotics such as CAZ, CFP, and carbapenem which were usually used to treat P. aeruginosa infections. However, more recently, bacteria including P. aeruginosa have acquired resistance to majority of antibiotics giving rise to increasing number of MDR strains  and limiting the therapeutic options for clinicians. Antibiotic susceptibility results revealed that PTZ, AMK, IMP, and CFP were the most effective antibiotics.
BL-BL inhibitor (BL/BLI) combinations such as PTZ or ticarcillin/clavulanic acid would be appropriate for treating infections with extended-spectrum beta-lactamase-producing bacteria. Although the bactericidal activity of BL/BLI combination with AMK is greater, the adverse effect of ototoxicity with systemic aminoglycoside use should be kept in mind. IMP is one of the most active drugs against P. aeruginosa found in CSOM;, however, the treatment of such infections with this drug has often lead to the emergence of IMP resistant mutants. Production of metallo-BLs and deficiency of outer membrane protein OprD are basic mechanisms of resistance to IMP in P. aeruginosa.
We observed highest degree of resistance against fluoroquinolones followed by antipseudomonal penicillins and aminoglycosides. Our findings were concurrent to studies published by various authors who also reported high degree of resistance to fluoroquinolones and aminoglycosides.,, In contrast, other researchers have reported a low level of resistance for these groups of drugs.,, Fluoroquinolones and aminoglycosides are broad-spectrum antibiotics used to treat various P. aeruginosa infections. Resistance to fluoroquinolones is basically a reflection to mutation, which is a result of selective pressure created by the use of it. Two major mechanisms may lead to fluoroquinolone resistance in P. aeruginosa: (i) modification of the primary target (DNA gyrase) and secondary target (topoisomerase IV) by point mutations in gyrA/gyrB and parC/par genes, respectively, and (ii) four efflux systems identified in P. aeruginosa. In the present study, high degree of resistance to aminoglycosides was also seen; however, TB and GM were found to be useful, first-line topical agents. fluoroquinolone and aminoglycoside otic drop preparations are the most commonly prescribed antibiotics to CSOM patients in our setup and probably this could be the reason for high degree of resistance to these group of drugs.
Although the risk of resistance to fluoroquinolones and also the ototoxicity due to aminoglycosides is a major concern, still in otolaryngology, CIP and GM otic drops are usually prescribed even if the isolated strains are resistant. The possible reason is that antibiotic concentration in otic drops in the middle ear and mastoid cavities is high enough to overcome the minimal inhibitory concentration of resistant strains.
PTZ, CAZ, CFP, and IMP showed good activity against the P. aeruginosa strains, but the absence of oral formulations of these drugs has severely limited the use of these antibiotics in CSOM patients. IMP is regarded as the final medication for MDRPA infections, but it is also important to limit the use of carbapenems in order to combat the appearance of other types of resistance. Strains resistant to CAZ, CFP, and IMP may be difficult to treat as such strains may require treatment with polymyxin, but it is associated with severe nephrotoxicity, and neurotoxicity thus limiting its use. As a drug of last resort, however, polymyxin alone or with a BL antibiotic has shown some success., Unless new drugs are developed, it is hard to escape the conclusion that MDRPA will be an increasing reality and that the use of polymyxins will increase, despite their toxicity.
Pseudomonas can thrive well in nutritionally deprived conditions; it proliferates at room temperature and is highly resistant to antibiotics, making it difficult to treat. Treatment modalities for CSOM vary according to the organism isolated and its antibiogram; moreover, approach to treat a sensitive strain is entirely different from the MDR strain. Prescription of illogical antibiotic combinations and in many cases economical constrains on patient part has also played a role in the development of antimicrobial resistance. In the present study, 47.1% (88/187) strains were designated as MDR strains, which is quite high. These drug-resistant strains can pose a significant risk of nosocomial infections to other patients. If such strains somehow get into the hospital setting, they are very difficult to eradicate and can be the clinicians worst nightmare. Infections caused by MDRPA strains can significantly contribute to pharmacotherapeutic and pharmacoeconomic losses from patient's perspective. It seems likely that most of this MDR reflects the accumulation of multiple mutations, although this surmise remains to be confirmed by molecular studies.
| Conclusion|| |
CSOM as similar to other chronic disease can limit an individual's employability and quality of life. With the development and widespread use of antibiotics, the types of pathogenic microorganisms and their resistance to antibiotics have changed. Before administering antibiotics either local or systemic, culture of aural discharge should be performed in all CSOM patients and the local antimicrobial susceptibility data should be utilized for formulating antibiotic policy for every institution as this will surely help in preventing the emergence and spread of resistant pathogens.
P. aeruginosa was found to be the predominant cause of CSOM in the present study with substantial number of strains being MDR. Hence, the judicial use of antibiotics is recommended with alternative measures to be considered for MDR strains.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Orji FT, Dike BO. Observations on the current bacteriological profile of chronic suppurative otitis media in Southeastern Nigeria. Ann Med Health Sci Res 2015;5:124-8.
] [Full text]
Kumar H, Seth S. Bacterial and fungal study of 100 cases of chronic suppurative otitis media. J Clin Diagn Res 2011;5:1224-7.
Rout MR, Mohanty D, Vijaylaxmi Y, Kamalesh B, Chakradhar M. Prevalence of cholesteatoma in chronic suppurative otitis media with central perforation. Indian J Otol 2012;18:7-10. [Full text]
Poorey VK, Thakur P. Clinicomicrobiological evaluation and antibiotic susceptibility in cases of chronic suppurative otitis media. Indian J Otol 2015;21:107-10. [Full text]
Loy AH, Tan AL, Lu PK. Microbiology of chronic suppurative otitis media in Singapore. Singapore Med J 2002;43:296-9.
Kapusuz Z, Keles E, Alpay HC, Karlidag T, Kaygusuz I, Uzunlar AK, et al.
The effect of topical ciprofloxacin and steroid-containing ear drops for chronic suppurative otitis media on the internal ear. Eur Arch Otorhinolaryngol 2010;267:35-41.
Prakash R, Juyal D, Negi V, Pal S, Adekhandi S, Sharma M, et al.
Microbiology of chronic suppurative otitis media in a tertiary care setup of uttarakhand state, India. N Am J Med Sci 2013;5:282-7.
Prakash M, Lakshmi K, Anuradha S, Swathi GN. Bacteriological profile and their antibiotic susceptibility pattern of cases of CSOM. Asian J Pharm Clin Res 2013;6:210-2.
Shyamala R, Reddy PS. The study of bacteriological agents of chronic suppurative otitis media: Aerobic culture and evaluation. J Microbiol Biotech Res 2012;2:152-62.
Aduda DS, Macharia IM, Mugwe P, Oburra H, Farragher B, Brabin B, et al.
Bacteriology of chronic suppurative otitis media (CSOM) in children in Garissa district, Kenya: A point prevalence study. Int J Pediatr Otorhinolaryngol 2013;77:1107-11.
Asish J, Amar M, Vinay H, Sreekantha, Avinash SS, Amareshar M. To study the bacteriological and mycological profile of chronic suppurative otitis media patients and their antibiotic sensitivity pattern. Int J Pharma Bio Sci 2013;4:186-99.
Kim SH, Kim MG, Kim SS, Cha SH, Yeo SG. Change in detection rate of methicillin-resistant Staphylococcus aureus
and Pseudomonas aeruginosa
and their antibiotic sensitivities in patients with chronic suppurative otitis media. J Int Adv Otol 2015;11:151-6.
Kazeem MJ, Aiyeleso R. Current bacteriological profile of chronic suppurative otitis media in a tertiary facility of Northern Nigeria. Indian J Otol 2016;22:157-61. [Full text]
Shyamala R, Reddy SP. Incidence and sensitivity pattern of Pseudomonas aeruginosa
in chronic suppurative otitis media in South Indian rural population. J Microbiol Biotech Res 2012;2:346-50.
Duiguid JP, Collee JG, Fraser AG. Laboratory strategy in the diagnosis of infective syndromes. In: Mackie and McCartney Practical Medical Microbiology. 14th
ed. London: Churchill Livingstone; 2006.
Forbes BA, Sham DF, Weissfeld AS. Bailey and Scott's Diagnostic Microbiology. 12th
ed. St. Louis, Misssouri, USA: Mosby Inc.; 2007.
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; 17th
Informational Supplement, CLSI Document M100-S17. Wayne PA: Clinical and Laboratory Standards Institute; 2007.
Falagas ME, Koletsi PK, Bliziotis IA. The diversity of definitions of multidrug-resistant (MDR) and pandrug-resistant (PDR) Acinetobacter baumannii
and Pseudomonas aeruginosa
. J Med Microbiol 2006;55(Pt 12):1619-29.
Livermore DM. Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa
: Our worst nightmare? Clin Infect Dis 2002;34:634-40.
Vishwanath S, Mukhopadhyay C, Prakash R, Pillai S, Pujary K, Pujary P. Chronic suppurative otitis media: Optimizing initial antibiotic therapy in a tertiary care setup. Indian J Otolaryngol Head Neck Surg 2012;64:285-9.
Nwokoye NN, Egwari LO, Coker AO, Olubi OO, Ugoji EO, Nwachukwu SC. Predisposing and bacteriological features of otitis media. Afr J Microbiol Res 2012;6:5205.
Osazuwa F, Osazuwa E, Osime C, Igharo EA, Imade PE, Lofor P, et al.
Etiologic agents of otitis media in Benin city, Nigeria. N Am J Med Sci 2011;3:95-8.
Ettehad GH, Refahi S, Nemmati A, Pirzadeh A, Daryani A. Microbial and antimicrobial susceptibility patterns from patients with chronic otitis media in Ardebil. Int J Trop Med 2006;1:62-5.
Singh AH, Basu R, Venkatesh A. Aerobic bacteriology of chronic suppurative otitis media in Rajahmundry. Biol Med 2012;4:73-9.
Nikakhlagh S, Khosravi AD, Fazlopour A, Safarzadeh M, Rashidi N. Microbiologic findings in patients with chronic suppurative otitis media. J Med Sci 2008;8:503-6.
Ikeda K, Misawa S, Kusunoki T. Comparative bactericidal activity of four fluoroquinolones against Pseudomonas aeruginosa
isolated from chronic suppurative otitis media. BMC Ear Nose Throat Disord 2015;15:5.
Gellatly SL, Hancock RE. Pseudomonas aeruginosa
: New insights into pathogenesis and host defenses. Pathog Dis 2013;67:159-73.
Song W, Woo HJ, Kim JS, Lee KM.In vitro
activity of beta-lactams in combination with other antimicrobial agents against resistant strains of Pseudomonas aeruginosa
. Int J Antimicrob Agents 2003;21:8-12.
Jang CH, Park SY. Emergence of ciprofloxacin-resistant pseudomonas in chronic suppurative otitis media. Clin Otolaryngol Allied Sci 2004;29:321-3.
Ahmed S, Iqbal MA, Hassan Z, Khurshid T, Ali L, Pervez Q. Spectrum and bacterial isolates in chronic suppurative otitis media in Khuzdar. Pak J Otolaryngol 2006;22:34-6.
Okamoto K, Gotoh N, Nishino T. Pseudomonas aeruginosa
reveals high intrinsic resistance to penem antibiotics: Penem resistance mechanisms and their interplay. Antimicrob Agents Chemother 2001;45:1964-71.
Wang CX, Mi ZH. Imipenem-resistant Pseudomonas aeruginosa
producing IMP-1 metallo-beta-lactamases and lacking the outer-membrane protein OprD. J Med Microbiol 2006;55(Pt 3):353-4.
Yeo SG, Park DC, Hong SM, Cha CI, Kim MG. Bacteriology of chronic suppurative otitis media – A multicenter study. Acta Otolaryngol 2007;127:1062-7.
Mansoor T, Musani MA, Khalid G, Kamal M. Pseudomonas aeruginosa
in chronic suppurative otitis media: Sensitivity spectrum against various antibiotics in Karachi. J Ayub Med Coll Abbottabad 2009;21:120-3.
Sheng WH, Chen YC, Wang JT, Chang SC, Luh KT, Hsieh WC. Emerging fluoroquinolone-resistance for common clinically important gram-negative bacteria in Taiwan. Diagn Microbiol Infect Dis 2002;43:141-7.
Falagas ME, Kasiakou SK. Colistin:The revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. Clin Infect Dis 2005 1;40:1333-41.
Falagas ME, Bliziotis IA, Kasiakou SK, Samonis G, Athanassopoulou P, Michalopoulos A. Outcome of infections due to pandrug-resistant (PDR) Gram-negative bacteria. BMC Infect Dis 2005;5:24.
[Table 1], [Table 2]