Periodontal disease in down syndrome: Predisposing factors and potential non-surgical therapeutic approaches.

BACKGROUND: Periodontal diseases (PDs) have been documented to be significantly more prevalent and severe in patients with Down syndrome (DS). Different immunological and microbiological factors contributed to predisposing these patients to progressive and recurrent PDs. AIM: The aim of this review was to investigate the altered immunological responses and oral microbiota disorders as well as focus on adjunctive non-surgical methods for the treatment of PDs and its applicability in patients with DS. MATERIAL AND METHODS: A literature review was conducted addressing the following topics: (1) the altered immunological responses, (2) orofacial disorders related to DS patients, (3) oral microbiota changing, and (4) adjunctive non-surgical treatment and its efficacy in patients with DS. RESULTS: Due to the early onset of PDs in children with DS, the need for prompt and effective treatment in these patients is essential. DISCUSSION AND CONCLUSION: So, investigating underlying factors may open a new window to better understand the pathology of PDs in DS people and thus, find better strategies for treatment in such group. Although non-surgical treatments such as photodynamic therapy and probiotic consumption represented acceptable outcomes in different examined patients without DS, data about the application of these convenience and no need for local anesthesia methods in patients with DS is limited.

Molecular Characterization of Resistance to Second-Line Anti-Mycobacterial Drugs among Clinical Isolates of Multidrug-Resistant Mycobacterium tuberculosis.

BACKGROUND: The emergence of multidrug resistance and extensively drug-resistant tuberculosis is a serious public health crisis. Using rapid and inexpensive molecular methods such as HRM assay in the detection of second-line drugs resistance in M. tuberculosis would be helpful in the treatment and control of XDR tuberculosis cases. METHODS: MDR-TB isolates were collected from Iranian tuberculosis laboratories. Drug susceptibility test performed via the indirect proportion method utilizing LJ Medium. Susceptibility to ciprofloxacin, ofloxacin, amikacin, kanamycin, and capreomycin, as second-line anti-tuberculosis agents were assessed. Single point mutations in gyrA, rrs and eis genes were detected via HRM assay and DNA sequencing. RESULTS: A DST test was performed for 56 MDR isolates and at least 27 (48.2%) isolates were resistant to CIP or OFL. Also, 14 (25%), 12 (21.4%), and 15 (26.7%) isolates were resistant to capreomycin, amikacin, and kanamycin, respectively. D94G, A90V, and G88C mutations were the most frequent mutations in gyrA gene. Also, A1401G mutation was detected more than the other mutations in rrs gene. CONCLUSIONS: The frequency of CIP/OFL and AMK/CAP/KAN-resistant TB is considerable among Iranian tuberculosis cases. HRM assay is a rapid and inexpensive test and can detect important mutation-based drug resistance in MDR-TB and XDR-TB isolates.

Molecular characterizations of antibiotic resistance, biofilm formation, and virulence determinants of Pseudomonas aeruginosa isolated from burn wound infection.

BACKGROUND: Burn injuries result in disruption of the skin barrier against opportunistic infections. Pseudomonas aeruginosa is one of the main infectious agents colonizing burn wounds and making severe infections. Biofilm production and other virulence factors along with antibiotic resistance limit appropriate treatment options and time. MATERIALS AND METHODS: Wound samples were collected from hospitalized burn patients. P. aeruginosa isolates and related virulence factors identified by the standard biochemical and molecular methods. Antibiotic resistance patterns were determined by the disc diffusion method and ß-lactamase genes were detected by polymerase chain reaction (PCR) assay. To determine the genetic relatedness amongst the isolates, enterobacterial repetitive intergenic consensus (ERIC)-PCR was also performed. RESULTS: Forty P. aeruginosa isolates were identified. All of these isolates were biofilm producers. Carbapenem resistance was detected in 40% of the isolates, and blaTEM (37/5%), blaVIM (30%), and blaCTX-M (20%) were the most common ß-lactamase genes. The highest resistance was detected to cefotaxime, ceftazidime, meropenem, imipenem and piperacillin, and 16 (40%) isolates were resistant to these antibiotics. The minimum inhibitory concentrations (MIC) of colistin was lower than 2 µg/mL and no resistance was observed. Isolates were categorized to 17 MDR, 13 mono-drug resistance, and 10 susceptible isolates. High genetic diversity was also observed among the isolates (28 ERIC types) and most carbapenem-resistant isolates were classified into four main types. CONCLUSION: Antibiotic resistance, particularly carbapenem resistance was considerable among the P. aeruginosa isolates colonizing burn wounds. Combining carbapenem resistance with biofilm production and virulence factors would result in severe and difficult-to-treat infections.

Brain Abscess Caused by Nocardia asteroides in a Diabetic Patient: A Rare Case Report.

Nocardial brain abscess is usually associated with immunodeficiency, but can sometimes emerge in healthy individuals. This infection can be acquired through inhalation or direct inoculation of the bacteria, followed by dissemination to various organs, including the brain, through blood circulation. Mortality rate due to nocardial cerebral abscess is three times higher than that associated with cerebral abscess caused by other types of bacteria. Moreover, patients with Nocardia asteroides-associated brain abscess show poorer prognosis compared to patients with brain abscess caused by other Nocardia species, which is probably due to the high tendency of N. asteroides to become resistant to numerous antibiotics. It is, therefore, of paramount importance to diagnose and treat N. asteroides cerebral abscess in patients as soon as possible. The current paper is a rare report of a brain abscess caused by N. asteroides in a diabetic patient who failed to respond to multiple antibiotics (trimethoprim/sulfamethoxazole and amikacin), but improved by receiving imipenem and linezolid, and was finally successfully treated by surgical operation and long-term antibiotic therapy (imipenem and linezolid).

Pulmonary Nocardia ignorata Infection in Gardener, Iran, 2017.

Nocardia ignorata, which was first described in 2001, is a rare human pathogen. We report a case of pulmonary nocardiosis caused by this bacterium in a 55-year-old man from Iran. The patient, a gardener, had frequent exposure to soil and may have acquired the infection from that source.

Antimicrobial combination effects against multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa strains: A cross-sectional study.

Background and Aims: Emergence of multidrug resistance in non-fermenting Gram-negative bacilli is a threat to public health. Combination therapy is a strategy for the treatment of antibiotic-resistant infections. Methods: In this cross-sectional study, a total of 63 nonduplicate clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa were collected from various specimens. Identification of bacterial isolates was performed by phenotypic and molecular tests. Antibiotic susceptibility patterns and detection of ß-lactamase genes were determined using the broth microdilution and polymerase chain reaction (PCR) techniques, respectively. Then, the combined effects analysis was determined by the checkerboard method. Based on the status of resistance to carbapenems (imipenem and meropenem), 25 isolates of each genus were selected for further investigation. Results: For A. baumannii, bla OXA-23, bla OXA-58, and bla OXA-48 genes were positive in 21 (84%), 17 (68%), and 11 (44%) of isolates, respectively. In P. aeruginosa isolates, bla VIM was the most common gene (44%) and other genes including bla IMP, bla NDM, and bla OXA-23 were found in nine (36%), six (24%), and three (12%) isolates, respectively. Meropenem (MER)-tigecycline (TIG) had a significant synergistic effect against 20 (80%) A. baumannii (p value < 0.001). This combination was also efficient against 5 (20%) P. aeruginosa isolates. Moreover, the other combination, tigecycline-amikacin (TIG-AMK) was effective against 10 (40%) A. baumannii isolates. The combination of colistin (COL) and MER showed a significant synergistic effect against 21 (84%) A. baumannii (p value < 0.001) and 17 (68%) P. aeruginosa isolates (p value < 0.001). Conclusion: The MER-TIG and COL-MER combinations are promising options against resistant bacteria. Our study could be helpful for the development of a new treatment recommendation.

Effects of non-tuberculous mycobacteria on BCG vaccine efficacy: A narrative review.

The Mycobacterium tuberculosis bacterial pathogen is responsible for the ongoing global tuberculosis (TB) epidemic. Bacille Calmette-Guérin (BCG), the only currently approved TB vaccine, is successful in preventing disseminated disease in newborns. However, it has a variable efficacy against pulmonary TB in adults. This protective effect of the vaccine varies greatly among different populations and geographical areas, which the increased exposure of particular populations to non-tuberculous mycobacteria (NTM) is considered as one of the reasons for this issue. Numerous studies have shown that exposure to NTM species causes the host immune system to be improperly primed. It has also been suggested that NTM species may be blamed for reduction in BCG vaccine effectiveness against M. tuberculosis. The increased exposure of certain populations to NTM has diverse effects on BCG efficacy. Moreover, the exposure to NTM can induce opposite effects on BCG efficacy depending on the NTM exposure route and survivability. A detailed understanding of the impact of NTM exposure on the efficacy of the BCG vaccine is essential for ongoing efforts to develop new TB vaccines as it may ultimately be a crucial success factor. The aim of this study was to review the findings of the studies focusing on the effects of NTM on BCG vaccine efficacy in animal models.

Klebsiella pneumoniae: an update on antibiotic resistance mechanisms.

Klebsiella pneumoniae colonizes mucosal surfaces of healthy humans and is responsible for one third of all Gram-negative infections in hospitalized patients. K. pneumoniae is compatible with acquiring antibiotic resistance elements such as plasmids and transposons encoding various ß-lactamases and efflux pumps. Mutations in different proteins such as ß-lactamases, efflux proteins, outer membrane proteins, gene replication enzymes, protein synthesis complexes and transcription enzymes also generate resistance to antibiotics. Biofilm formation is another strategy that facilitates antibiotic resistance. Resistant strains can be treated by combination therapy using available antibiotics, though proper management of antibiotic consumption in hospitals is important to reduce the emergence and proliferation of resistance to current antibiotics.

Characterization of virulence factors and antibacterial activity of curcumin in hypervirulent Klebsiella pneumoniae.

Aim:Klebsiella pneumoniae is a threat to human health due to its carbapenem-resistance and hypervirulent phenotype. Curcumin is a well-known antimicrobial agent. Hence, it is important to investigate the antivirulence activity of curcumin against hypervirulent K. pneumoniae isolates. Materials & methods: Carbapenemase presence and prevalence of hypervirulent isolates were determined. Inhibition of biofilm formation and expression of virulence genes were analyzed by colorimetry and real-time PCR tests. Results: Sixteen hypervirulent K. pneumoniae isolates were identified. The optimum activity of curcumin was detected at 1/2 minimum inhibitory concentration. Curcumin possessed appropriate antibiofilm, anti-efflux and anticapsule activities. Conclusion: According to the crucial role of biofilm, capsule and efflux systems in the pathogenesis of hypervirulent K. pneumoniae, curcumin may be used to improve anti-Klebsiella treatment.

Effects of statins on myocarditis: A review of underlying molecular mechanisms.

Myocarditis refers to the clinical and histological characteristics of a diverse range of inflammatory cellular pathophysiological conditions which result in cardiac dysfunction. Myocarditis is a major cause of mortality in individuals less than 40 years of age and accounts for approximately 20% of cardiovascular disease (CVD) events. Myocarditis contributes to dilated cardiomyopathy in 30% of patients and can progress to cardiac arrest, which has a poor prognosis of <40% survival over 10 years. Myocarditis has also been documented after infection with SARS-CoV-2. The most commonly used lipid-lowering therapies, HMG-CoA reductase inhibitors (statins), decrease CVD-related morbidity and mortality. In addition to their lipid-lowering effects, increasing evidence supports the existence of several additional beneficial, 'pleiotropic' effects of statins. Recently, several studies have indicated that statins may attenuate myocarditis. Statins modify the lipid oxidation, inflammation, immunomodulation, and endothelial activity of the pathophysiology and have been recommended as adjuvant treatment. In this review, we focus on the mechanisms of action of statins and their effects on myocarditis, SARS-CoV-2 and CVD.

Pulmonary Nocardiosis in Pemphigus Vulgaris Patients from Tehran, Iran.

OBJECTIVE: Nocardiosis is an opportunistic infection in individuals who had organ transplants and in patients with immunosuppressive diseases such as pemphigus Vulgaris (PV), diabetes mellitus, and HIV. Nocardiosis rate has not been assessed in Iranian PV patients, and this was the first study to estimate nocardiosis rate in these patients. METHODS: In this study, 103 patients with PV were examined. BAL samples were obtained and direct smear was prepared and visualized by microscopy after PAS staining. Samples were cultured on antibiotic-containing blood and chocolate agar media. DNA extraction and PCR were performed on positive cultures, and final identification was done by 16S rRNA gene sequencing. Drug susceptibility testing was done by microbroth dilution method. RESULTS: Four positive cultures (3.88%) were found in the samples (n = 103). According to sequence analysis, 2 isolates were identified as Nocardia cyriacigeorgica and 2 as Nocardia otitidiscaviarum and Nocardia cerradoensis. Nocardia cerradoensis was isolated from an invasive brain infection. Isolated bacteria were susceptible to majority of the tested antibiotics, except for 2 strains of Nocardia cyriacigeorgica and Nocardia cerradoensis. This was the first isolation of Nocardia cerradoensis of human infection in Asia. Patients with PV are susceptible to nocardiosis, similar to other immunocompromised patients. CONCLUSION: Pemphigus Vulgaris is a severe autoimmune disease which is treated by a high dosage of corticosteroids. Opportunistic infections are one of the greatest challenges of these patients. One of the neglected agents of opportunistic infection in this disorder is Nocardiosis which can cause a high mortality rate in PV patients.

Genotyping and Drug Susceptibility Patterns of M. Tuberculosis Isolated from HIV Seropositive Patients in Tehran Iran.

AIM: This study aims to investigate the prevalence and drug-resistance M. tuberculosis isolated from HIV seropositive individuals in Tehran, Iran. BACKGROUND: Human immunodeficiency virus (HIV) is one of the most important risk factors for developing active tuberculosis (TB). OBJECTIVE: The objective is to determine the rate of transmission and drug-resistant M. tuberculosis (MTB) strains isolated from HIV seropositive patients in Tehran province, Iran. METHODS: This study consecutively enrolled 217 TB/HIV coinfected patients from April 2018 to August 2019 at Emam Khomeini referral hospital and 5 other health centers in Tehran province. The isolates were genotyped using 15 loci Mycobacterial interspersed repetitive unit-variable number tandem repeats (MIRU-VNTR). Minimum inhibitory concentration (MIC) was determined for 6 drugs. In addition, mutations were assessed in rpoB, katG, inhA, and ahpC genes using Reverse Blot Hybridization Assay System. RESULTS: A 20 (9.2%) patients were culture-positive for M. tuberculosis and typed by MIRU-VNTR, 13 (65%) strains formed 5 clusters, but 6 (30%) isolates had a unique pattern. The total Hunter- Gaston discrimination index (HGDI) for all 15 loci was 0.846, and the cluster size was 2 to 4 patients. The estimated proportion of recent transmission was 45%. The mutation was identified in 1 isolate, lost inhAW1 and mutation in MT1 loci, which was resistant to isoniazid (INH). Moreover, 1 (5%) and 3 (15%) isolates were resistant to INH and ethambutol (EMB), respectively, of which 1 was resistant to INH and EMB. CONCLUSION: The transmission rate of TB in HIV patients was relatively high; however, the prevalence of drug-resistant strains and TB infection in females was insignificant in this study (p < 0.05); none of the isolates was MDR strains.

Incidence, Clinical Manifestation, Treatment Outcome, and Drug Susceptibility Pattern of Nontuberculous Mycobacteria in HIV Patients in Tehran, Iran.

BACKGROUND: Nontuberculous mycobacterial (NTM) infections have radically increased worldwide due to the increase in HIV infections. The disease activity increases with progressive immunodeficiency. METHODS: A total of 216 HIV seropositive patients suspected of having mycobacterial infection were recruited for this study. Clinical samples were collected from each patient and cultured on Lowenstein-Jensen media. Detection and species identification were simultaneously done using Reverse Blot Hybridization Assay System. Also, the minimum inhibitory concentrations (MIC) for each isolate were determined in 7H9 broth media for 10 antibiotics. RESULTS: In this study, 4 rapid and 4 slow-growing NTM species were isolated and identified. Mycobacterium fortuitum was the most common NTM species, 3/8 (37.5%), followed by Mycobacterium kansasii, 2/8 (25%). The cases were identified as pulmonary disease, 5/8 (62.5 %), disseminated infection, 2/8 (25%), and skin abscess, 1/8 (12.5%). M. chelonae and Mycobacterium avium were isolated from patients diagnosed with disseminated infection with treatment failure. The skin abscess was caused by infection with M. simiae. The results of the MIC testing were as follows: M. kansasii and M. fortuitum were susceptible to amikacin (AMK); M. avium to clarithromycin (CLA); M. fortuitum 2/3 (67%) to ciprofloxacin (CIP); 1/2 (50%) of M. kansasii isolates to CLA, and M. chelonae to rifampin (RIF), linezolid (LIN), AMK, and CIP at medium and high concentrations. CONCLUSION: AMK showed incredible in vitro activity against M. kansasii and M. fortuitum. Also, M. avium was susceptible to CLA, whereas M. simiae and M. chelonae were resistant to the tested drugs in this study.

Multiple Myeloma or Brucellosis: A Case Report.

BACKGROUND: Brucellosis, a major health problem in developing countries, is a multisystem infection with a broad spectrum of clinical manifestations. Hematological complications, ranging from an intravascular coagulopathy to mild homeostasis disorders (such as gammopathy), have been reported in brucella infection. These signs and symptoms may lead to misdiagnosis of brucellosis with other hematological diseases. CASE: A 65-year-old male whose occupation was shepherding was referred to our hospital as a known case of multiple myeloma with continuous fever, muscle weakness, and night sweating after taking 2 courses of chemotherapy. The laboratory diagnosis of multiple myeloma had been based on the observation of a high percent of plasma cells in the bone marrow aspiration. At follow- up, the result of patient's fever workup, with 2 sets of blood cultures, was positive for Brucella melitensis. Isolated brucella was confirmed as B. melitensis by 16S rRNA sequencing. Brucellosis serologic test was performed by agglutination test and positive results were obtained. The patient was discharged with the cessation of fever and general improvement after the end of the parental treatment phase of brucella bacteremia. CONCLUSIONS: Brucella infection may cause a severe disease, mimicking a primary hematological disease, which could complicate the correct diagnosis. In brucellosis cases, due to the wide range of symptoms, in addition to cultivation and serological methods, molecular methods should also be used to prevent inappropriate diagnosis and additional costs.

The first report of Pseudomonas oryzihabitansin infection in a patient with hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is one of the neglected chronic inflammatory disorders which has not efficient treatment. These patients were susceptible to various infectious diseases because of their changes in immuneresponse. Also, HS pathogenesis remains unclear and its report can create novel insight into mechanism and pathogenesis of this infection. Moreover, given that different susceptibility patterns of Pseudomonas spp this species should be identified to the species level; molecular methods are rapid, inexpensive, and reliable method for identification of infectious agents to the species level and appropriate treatment of infections.

Correlation between biofilm formation and carbapenem resistance among clinical isolates of Klebsiella pneumoniae.

BACKGROUND: Klebsiella pneumoniae is a Gram-negative enteric bacterium that causes nosocomial infections; this bacterium has survived from harsh condition using biofilm formation in hospital equipment and cause severe infection. In the other hand, the emergence and extension of carbapenem resistance burden among K. pneumonia producing biofilm is the current concern of public health services. There are controversial findings about this subject. The aim of this study was to evaluate the correlation between biofilm formation and resistance to carbapenem among clinical isolates of K. pneumoniae. METHODS: A total of 160 K. pneumoniae isolates were collected from various infections of hospitalized patients. The Carba NP test and molecular methods were used for detection of carbapenem resistance isolates of K. pneumonia. Subsequently, the ability for biofilm production was performed from all isolates. Finally, Correlation of biofilm formation among carbapenem resistant isolates was calculated using χ2 and Fisher's exact tests. RESULTS: Among K. pneumoniae isolates 42.5% have carbapenemase activity by Carba NP test, while carbapenemase genes were detected in 35.6% of isolates in amplification assay. Moreover, there are 52.5% (n= 84) of all isolates were formed a strong biofilm, while 38.1% (n= 61) and 9.3% (n= 15) of isolates were middle and weak biofilm producer, respectively. Among carbapenem resistant cases (n= 68), there are 77.9% (n= 53) and 22% (n= 15) of isolates were reported as strong and middle biofilm producer, respectively. We see a significant correlation was seen between biofilm formation ability and carbapenem resistant isolates (p-value < 0.00001). CONCLUSION: The increase of carbapenem resistance burden in biofilm producing isolates of K. pneumoniae is considered as serious alert and the basic measures to combat this phenomenon is imperative.

Detection of Nocardia, Streptomyces and Rhodococcus from bronchoalveolar lavage specimens of patients with HIV by Multiplex PCR Assay.

BACKGROUND: Nocardia, Streptomyces and Rhodococcus are life threatening opportunistic pathogens under immunodeficiency conditions, particularly among patients infected with HIV. Rapid and accurate detection of these infections can improve immune health quality, patient management and appropriate treatment. The aim of this study was to design a novel multiplex-PCR assay for rapid diagnosis of these three organisms directly from bronchoalveolar lavage (BAL) specimens of patients infected with HIV. METHODS: The genus specific primers were designed for direct-detection of Nocardia, Streptomyces and Rhodococcus in a single tube multiplex PCR. This PCR specifically amplified the target genes from pure cultures. It subsequently was applied on BAL specimens of 29 HIV positive patients that had previously been culture negative for actinomycete bacteria, of which Nocardia, Streptomyces and Rhodococcus are members. RESULTS: Of 29 respiratory clinical specimens, there were positive for Nocardia spp. and one was positive for Streptomyces spp using the multiplex PCR assay. The sequencing of the PCR products identified the species as Nocardia cyriacigeorgica (n=2), Nocardia farcinica and Streptomyces albus. CONCLUSION: This novel multiplex PCR assay yielded reliable results for accurate identification of Nocardia, Streptomyces and Rhodococcus from BAL while the results of bacterial culture were negative.

Prevalence of methicillin-resistant Staphylococcus aureus isolated from burn patients in Iran: A systematic review and meta-analysis.

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is considered a major cause of infection and mortality in burn patients, especially when nosocomially acquired. However, limited information is available on the prevalence of MRSA among burn patients in Iran. METHODS: A systematic search was performed using different electronic databases including Medline (via PubMed), Embase, Web of Science and Iranian Database. A meta-analysis was performed using Comprehensive Meta-Analysis Software (BioStat v.2.2). Use of a fixed- or random-effects model was used based on a heterogeneity test, and publication bias was assessed using Begg rank correlation and Egger weighted regression methods. RESULTS: Of 555 articles published from January 2000 to January 2016, 13 studies were included in this review. The meta-analyses showed that the prevalence of MRSA infection in burn patients was 77.9% (95% confidence interval 70.2-84.0%) among culture-positive cases. CONCLUSIONS: The results of this study indicate that the prevalence of MRSA among burn patients is very high in Iran. Thus, a comprehensive infection control strategy based on hand hygiene, education and training in antibiotic prescribing, environmental cleaning, contact precautions, good antibiotic stewardship and an active surveillance system on the basis of international criteria is urgently needed.

Community Acquired Pseudomonas Aeruginosa Pneumonia in a Young Athlete Man: A Case Report and Literature Review.

Pseudomonas aeruginosaisa commonly known as nosocomial infection agent but rarely previously healthy people are infected by P. aeruginosa. Here we report Community Acquired Pneumonia (CAP) in a 27 year old male athlete. 15 published P. aeruginosa CAP case reports were reviewed. 53.3% of patients were female and 46.67% were male. The mean age was 44 years old (SD: ±13.54). In 8 reports it is mentioned that the patient was a smoker. Fatality rate was 46.6% and death rate was not significantly different between selected antibiotic regimen, sex and smoking in patient's outcome. Chest strike can be a risk factor for P. aeruginosa CAP in athlete people. Our reported patient treated by ciprofloxacin 500 mg per day and healed without any Secondary complication. Fast, timely diagnosis and treatment is critical in Community Acquired P. aeruginosa pneumonia outcome.

Variable spontaneous mutation rate in clinical strains of multidrug-resistant Acinetobacter baumannii and differentially expressed proteins in a hypermutator strain.

BACKGROUND: The emergence of multidrug resistant Acinetobacter baumannii within hospitals poses a significant threat to patients. The inherent rate of mutation of these strains has not been described nor has the mechanism by which drug resistance arises. METHODS: Here, we determined the spontaneous mutation rates in 93 clinical strains of A. baumannii using fluctuation analysis. To rule out the clonal relatedness of hypermutator strains, pulsed-field gel electrophoresis (PFGE) was conducted. Using a combination of two-dimensional gel electrophoresis (2-DE) and MALDI-TOF mass spectrometry, the differentially expressed proteins of a hypermutator and a reference strain were identified. RESULTS: The spontaneous mutation rate of multi-drug resistant A. baumannii strains varied broadly from 0 to 2.1×10-6 mutation per cell division. The mutation rate in three multidrug resistant A. baumannii (MDR-AB) strains was found to be 1.63×10-6 (95% confidence interval (CI): 1×10-6-2×10-6), 2.1×10-6 (95% CI: 2×10-6 - 3×10-6), and 1.78×10-8 (95% CI: 9.29×10-9 2.95×10-8), consistent with a hypermutator phenotype. This rate is approximately 1000-fold higher than the average mutation rate in other MDR-ABs. PFGE of the three hypermutator strains indicate that they belong to distinct clones. Proteomic analysis of one hypermutator strain revealed 31 differentially expressed proteins including three with sizes of 51.2, 20.9, and 11.9kDa, which corresponded to a serine protease, a polyisoprenoid-binding protein, and the peptidoglycan binding protein, LysM. The serine protease was expressed only in the hypermutator strain, whereas the polyisoprenoid-binding protein and the peptidoglycan binding protein LysM were down-regulated 1.6 and 3-fold, respectively, in the hypermutators strain. CONCLUSION: Hypermutator A. baumannii strains occur with a low, but appreciable frequency among clinical multi-drug resistant isolates. The presence of hypermutator clinical isolates raises concerns that they may contribute to the failure of antibiotic treatment in infected patients and confound the interpretation of in vitro antibiotic susceptibility testing. The differentially expressed proteins involved in biofilm suppression and oxidative stress response, may represent adaptations derived from the hypermutator phenotype, a hypothesis that needs further testing.