Management Of Multidrug-resistant Research Articles

Bacterial Profile, Antimicrobial Susceptibility Pattern, and Associated Factors among Dental Caries-Suspected Patients Attending the Ayder Comprehensive Specialized Hospital and Private Dental Clinic in Mekelle, Northern Ethiopia.

Background Dental caries is a major public oral infectious disease globally due to its high prevalence and significant social impact. Many studies have been conducted on dental caries in Ethiopia; however, they fail to convey the antimicrobial resistance in the oral environment. Objective This study was conducted to determine the antimicrobial susceptibility patterns and biofilm formation in the bacteria isolated from dental caries and its associated factors of dental caries in THE Ayder Comprehensive Specialized Hospital and private dental clinics located at Mekelle, Ethiopia. Methods A cross-sectional study was conducted from September 2019 to October 2020. Sociodemographic characteristic, behavioral, and clinical data were collected using structured questionnaires. A total of 422 dental caries-suspected patients were selected and coronal caries scraps were collected by the dentist aseptically; these samples were transported to a microbiological laboratory to identify the antibiotic sensitivity assay and biofilm formation by the isolated pathogens. The data was analyzed using SPSS version 22. The P value of ≤0.05 was considered statistically significant. Results The overall prevalence of culture-positive samples was found to be 196 (46.4%). From the 196 culture-positive samples, 327 bacteria were isolated. Out of 327 bacterial isolates, 196 (46.4%) were identified as Streptococcus mutans and 69 (35.2%) were identified to be Staphylococcus aureus. From the isolated bacteria, 311 (95.1%) organisms were identified as positive for biofilm formation. From the AST assay, we have identified that penicillin has the highest resistance rate of 76.5%, followed by tetracycline at 64.8%. In contrast, the antibiotics such as cefoxitin and chloramphenicol have a sensitivity of 83.5% and 81.6% to all the bacterial isolates. The overall prevalence of multidrug resistance (MDR) in the isolates was found to be 40.4%. With respect to the associated risk factors, the white spot (AOR = 3.885, 95% CI 1.282-11.767, P = 0.016), gum bleeding (AOR = 2.820, 95% CI 1.006-7.907, P = 0.049), toothache (AOR = 2.27, 95% CI 0.58-0.885, P = 0.033), and chocolate consumption (AOR = 5.314, 95% CI 1.760-16.040, P = 0.003) were statically associated with dental caries bacterial infection. Conclusion Based on our findings, we recommend the integration of routine culture and AST into clinical practice that might support the diagnosis and management of MDR in dental caries. The education on proper dietary habits might support the prevention and control of dental caries. It is important to provide health education on how to improve oral health in the study area. The education on proper dietary habits might support the prevention and control of dental caries. Further study is needed to find the other determinant factors of dental caries.

Management of community-acquired pneumonia because of multidrug-resistant Pseudomonas aeruginosa with Supime: A case study

Community-acquired pneumonia (CAP), particularly in patients infected with multidrug resistance (MDR) Gram-negative bacilli, is a common and potential serious associated illness leading to considerable morbidity and mortality. Pseudomonas aeruginosa is the second most common pneumonia-causing pathogen, followed by K. pneumonia and S. aureus in India. This resistance is one of the most barriers to bacterial eradication and clinical cure of Pseudomonas infection. This delay in the management of MDR Pseudomonas aeruginosa with antibiotics can lead to increased mortality and morbidity. Here we discuss a case of a CAP caused by pathogen Pseudomonas aeruginosa which was resistant to the first line of antibiotics, piperacillin-tazobactam & cefoperazone sulbactam but sensitive to Supime (cefepime + sulbactam). Supime 3gm BD with 30 minutes of infusions for 7 days was effective in treating and discharging the patient from the hospital. Supime was safe and efficacious to treat hospitalized CAP patient infected with MDR Pseudomonas aeruginosa.

The Epidemiology and Pathogenesis and Treatment of Pseudomonas aeruginosa Infections: An Update.

Pseudomonas aeruginosa is a Gram-negative bacterial pathogen that is a common cause of nosocomial infections, particularly pneumonia, infection in immunocompromised hosts, and in those with structural lung disease such as cystic fibrosis. Epidemiological studies have identified increasing trends of antimicrobial resistance, including multi-drug resistant (MDR) isolates in recent years. P. aeruginosa has several virulence mechanisms that increase its ability to cause severe infections, such as secreted toxins, quorum sensing and biofilm formation. Management of P. aeruginosa infections focuses on prevention when possible, obtaining cultures, and prompt initiation of antimicrobial therapy, occasionally with combination therapy depending on the clinical scenario to ensure activity against P. aeruginosa. Newer anti-pseudomonal antibiotics are available and are increasingly being used in the management of MDR P. aeruginosa.

Antimicrobial stewardship and oxazolidinones use, a consideration for a Zambian health system

Antimicrobial stewardship is the organized and systematic way of educating and enforcing evidence-based prescribing ofantimicrobial agents to control misuse and overuse of antibiotics with the aim of curbing antimicrobial resistance. There is need to initiate antimicrobial stewardship program at various levels in the health sector such as health facilities or hospitals in order to safeguard and sustain the current antimicrobial agents in use. In addition, oxazolidinones are potentdrugs in management of multidrug resistance (MDR) related infections and linezolid is already on the market and being considered as a drug of 'last resort' for the treatment of MDR bacterial infections. Therefore, to avert the development and rapid spread of drug resistance against linezolid and other oxazolidinone drugs, antimicrobial stewardship program needs to be established for critical monitoring and regulation of their use at all critical levels in the health system hierarchy, especially in resource limited countries.

Antimicrobial stewardship and oxazolidinones use, a consideration for a Zambian health system

Antimicrobial stewardship is the organized and systematic way of educating and enforcing evidence-based prescribing ofantimicrobial agents to control misuse and overuse of antibiotics with the aim of curbing antimicrobial resistance. There is need to initiate antimicrobial stewardship program at various levels in the health sector such as health facilities or hospitals in order to safeguard and sustain the current antimicrobial agents in use. In addition, oxazolidinones are potentdrugs in management of multidrug resistance (MDR) related infections and linezolid is already on the market and being considered as a drug of 'last resort' for the treatment of MDR bacterial infections. Therefore, to avert the development and rapid spread of drug resistance against linezolid and other oxazolidinone drugs, antimicrobial stewardship program needs to be established for critical monitoring and regulation of their use at all critical levels in the health system hierarchy, especially in resource limited countries.

Mycoplasma genitalium infections: current treatment options and resistance issues.

Mycoplasma genitalium is one of the important causes of non-gonococcal urethritis. Rising incidence and emerging antimicrobial resistance are a major concern these days. The poor clinical outcomes with doxycycline therapy led to the use of azithromycin as the primary drug of choice. Single-dose azithromycin regimen over a period of time was changed to extended regimen following studies showing better clinical cures and less risk of resistance development. However, emerging macrolide resistance, either due to transmission of resistance or drug pressure has further worsened the management of this infection. The issues of drug resistance and treatment failures also exist in cases of M. genitalium infection. At present, the emergence of multidrug-resistant (MDR) M. genitalium strains is an alarming sign for its treatment and the associated public health impact due to its complications. However, newer drugs like pristinamycin, solithromycin, sitafloxacin, and others have shown a hope for the clinical cure, but need further clinical trials to optimize the therapeutic dosing schedules and formulate appropriate treatment regimens. Rampant and inappropriate use of these newer drugs will further sabotage future attempts to manage MDR strains. There is currently a need to formulate diagnostic algorithms and etiology-based treatment regimens rather than the syndromic approach, preferably using combination therapy instead of a monotherapy. Awareness about the current guidelines and recommended treatment regimens among clinicians and local practitioners is of utmost importance. Antimicrobial resistance testing and global surveillance are required to assess the efficacy of current treatment regimens and for guiding future research for the early detection and management of MDR M. genitalium infections.

Anti-mycobacterial Activity of Selected Indian Botanicals Using Surrogate Mycobacterium Strains

The aim of the present study was to validate the traditional claims of selected botanicals such as as Amorphophyllus sylvaticus, Andrographis paniculata, Corallocarpus epigaeus, Dioscorea bulbifera (L), Dioscorea oppositifolia (L), Dioscorea pentaphylla (L), Dioscorea hispida (Dennst), Enicostema axillare (Lam Raynal), Gloriosa superba (L) and Morinda citrifolia (L) as possible inhibitors of Mycobacterial strains. Different solvent extracts along with flavonoid and alkaloid fractions of the selected ten medicinal plants were evaluated for their antimycobacterial activity against Mycobacterium smegmatis (NCIM 5138) and Mycobacterium phlei (NCIM 2240). The minimum inhibitory concentrations (MICs) were calculated for determining the efficacy of the selected botanicals. As a measure of quality control, High Performance Thin Layer Chromatography (HPTLC) fingerprint of flavonoids and alkaloids of the selected plants were also developed and the Rf values of individual samples were recorded. Amongst the tested plants only Andrographis paniculata, Morinda citrifolia, and Enicostema axillare were observed to be effective growth inhibitors of selected less virulent Mycobacterium strains, however the chloroform extract of A. paniculata was observed to be most effective growth inhibitor of M. smegmatis (MIC=10 mg/ml) and M. phlei (MIC=10 mg/ml). The results of the present study revealed that the botanicals like Andrographis paniculata, Morinda citrifolia, and Enicostema axillare can be considered as an important resource for the identification of novel leads against Mycobacterial strains, which perhaps can be further explored for the management of multi drug resistance in treating tuberculosis.

A peptide derived from phage display library exhibits anti-tumor activity by targeting GRP78 in gastric cancer multidrug resistance cells

Multidrug resistance (MDR) remains a significant challenge to the clinical treatment of gastric cancer (GC). In the present study, using a phage display approach combined with MTT assays, we screened a specific peptide GMBP1 (Gastric cancer MDR cell-specific binding peptide), ETAPLSTMLSPY, which could bind to the surface of GC MDR cells specifically and reverse their MDR phenotypes. Immunocytochemical staining showed that the potential receptor of GMBP1 was located at the membrane and cytoplasm of MDR cells. In vitro and in vivo drug sensitivity assays, FACS analysis and Western blotting confirmed that GMBP1 was able to re-sensitize MDR cells to chemical drugs. Western blotting and proteomic approaches were used to screen the receptor of GMBP1, and GRP78, a MDR-related protein, was identified as a receptor of GMBP1. This result was further supported by immunofluoresence microscopy and Western blot. Additionally, Western blotting demonstrated that pre-incubation of GMBP1 in MDR cells greatly diminished MDR1, Bcl-2 and GRP78 expression but increased the expression of Bax, whereas downregulation of GRP78, function as a receptor and directly target for GMBP1, only inhibited MDR1 expression. Our findings suggest that GMBP1 could re-sensitize GC MDR cells to a variety of chemotherapeutic agents and this role might be mediated partly through down-regulating GRP78 expression and then inhibiting MDR1 expression. These findings indicate that peptide GMBP1 likely recognizes a novel GRP78 receptor and mediates cellular activities associated with the MDR phenotype, which provides new insight into research on the management of MDR in gastric cancer cells.

Current review of antimicrobial treatment of nosocomial pneumonia caused by multidrug-resistant pathogens

Nosocomial pneumonia (including ventilator-associated pneumonia; VAP), a consistently difficult-to-treat entity, is frequently caused by multidrug-resistant (MDR) or pandrug-resistant (PDR) bacteria. Given the high mortality rates caused by drug-resistant bacteria and the difficulty of developing new potent antibiotics to target the problematic pathogens, combination regimens are under ardent evaluation as new strategies to overcome increasing drug resistance. Adjustment of the administration method of certain β-lactams (meropenem, or imipenem/cilastatin), or combination of tigecycline with some agents, may show promise with regard to successful management of MDR or PDR Acinetobacter baumannii pneumonia. Additionally, vancomycin plus rifampicin is an effective regimen against nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) responding poorly to vancomycin monotherapy. The clinical appropriateness of parenteral colistin against pneumonia caused by MDR A. baumannii has been established in a clinical trial. Facing the decline of clinical vancomycin efficacy after initial use, linezolid might be the drug of choice with regard to the treatment of MRSA-VAP. The role of tigecycline monotherapy for the management of nosocomial pneumonia caused by MRSA and extended-spectrum β-lactamase-producing Enterobacteriaceae needs to be cautiously evaluated.

Clinical pharmacology and lesion penetrating properties of second- and third-line antituberculous agents used in the management of multidrug-resistant (MDR) and extensively-drug resistant (XDR) tuberculosis.

Failure of first-line chemotherapy to cure tuberculosis (TB) patients occurs, in part, because of the development of resistance to isoniazid (INH) and rifampicin (RIF) the two most sterilizing agents in the four-drug regimen used to treat primary infections. Strains resistant to both INH and RIF are termed multidrug-resistant (MDR). Treatment options for MDR patients involve a complex array of twenty different drugs only two classes of which are considered to be highly effective (fluoroquinolones and aminoglycosides). Resistance to these two classes results in strains known as extensively drug-resistant (XDR) and these types of infections are becoming increasingly common. Many of the remaining agents have poorly defined pharmacology but nonetheless are widely used in the treatment of this disease. Several of these agents are known to have highly variable exposures in healthy volunteers and little is known in the patients in which they must be used. Therapeutic drug monitoring (TDM) is infrequently used in the management of MDR or XDR disease yet the clinical pharmacokinetic studies that have been done suggest this might have a large impact on disease outcome. We review what is known about the pharmacologic properties of each of the major classes of second- and third-line antituberculosis agents and suggest where judicious use of TDM would have the maximum possible impact. We summarize the state of knowledge of drug-drug interactions (DDI) in these classes of agents and those that are currently in clinical trials. Finally we consider what little is known about the ability of TB drugs to reach their ultimate site of action--the interior of a granuloma by penetrating the diseased lung area. Careful consideration of the pharmacology of these agents is essential if we are to avoid further fueling the growing epidemic of highly drug-resistant TB and critical in the development of new antituberculosis drugs.

Extensively Drug-resistant Tuberculosis, Italy and Germany

To the Editor: Twenty-three countries have reported >1 case of extensively drug-resistant tuberculosis (XDR TB) (1); however, information about XDR TB is still incomplete. In particular, the response of XDR TB to treatment in countries with low incidence is not known. We compared mortality rates from XDR TB with those from multidrug-resistant (MDR) TB. We analyzed data from all culture-confirmed TB cases diagnosed during 2003–2006 by the TB clinical reference centers in Italy (Sondalo, Milan, Rome) and Germany (Borstel, Grosshansdorf, Bad-Lippspringe) and reviewed original clinical records. Drug susceptibility testing for first- and second-line anti-TB drugs was performed according to World Health Organization (WHO) recommendations by quality-assured laboratories and retested at WHO Supranational Reference Laboratories (Rome/Milan; Borstel) (2–4). XDR TB was defined as resistance to at least rifampin and isoniazid (MDR TB definition) in addition to any fluoroquinolone and >1 of 3 injectable anti-TB drugs (capreomycin, kanamycin, amikacin) (3). Characteristics of MDR TB and XDR TB cases were compared by χ2 test (categorical variables), Student t test (admission days), and Kaplan-Maier curve (sputum smear, culture conversion), where appropriate. Of 2,888 culture-positive TB cases analyzed (Italy 2,140, Germany 748), 126 (4.4%) were MDR (Italy 83, Germany 43) and 11 (0.4%) were XDR (Italy 8, Germany 3). We estimate that the TB cases analyzed represent 24% of culture-positive cases reported in Italy (69.7% of MDR) and 4.2% of those reported in Germany (12.6% of MDR). XDR TB was diagnosed in each year of the study. All 11 XDR TB patients were receiving retreatment, and of the 126 MDR TB patients, 74 (58.7%) were receiving retreatment. All XDR TB patients were HIV seronegative; and of 109 MDR TB patients tested for HIV, 10 (9.2%) were HIV seropositive. Details about previous treatment regimens, drug resistance, and duration of treatment of XDR TB patients are summarized in the Appendix Table. XDR TB patients were significantly more likely than MDR TB patients to be resistant to all first-line drugs (8/11 vs. 36/126, p<0.005); 2 of these patients were resistant to all tested drugs (Appendix Table). In Germany, nonnationals accounted for 95.3% (41/43) of MDR-TB cases and 100% (3 of 3) of XDR TB cases (all from the former Soviet Union); in Italy, they accounted for 72.3% (60/83) and 50% (4/8), respectively (p 45 years of age (64% [7/11] and 23% [29/126], respectively, p<0.01). Radiologic patterns of the thorax did not differ between XDR TB and MDR TB patients. In the overall sample, the only variable significantly associated with death (other than XDR TB status) was immigrant status (p<0.01). The association between XDR TB status and risk for death remained significant after stratification by immigrant status (p<0.05). Our findings suggest that mismanagement of TB cases plays a major role in emergence of the problem in Europe (along with suboptimal infection control in congregate settings) (5), while in high HIV-prevalence settings (e.g., South Africa) XDR TB was mainly observed in patients never treated previously (6). Mortality rates among MDR TB patients treated in reference centers (6.3%) were lower than the rate observed in a previous study in general hospitals in Italy (8.7%) (5), although a proportion of our MDR TB patients are still completing treatment. This difference in rates is probably due to better management of MDR in the reference centers. Because of the high proportion of XDR TB patients still receiving treatment, further follow-up is necessary to assess potential for cure. The clinical relevance of resistance to all first-line drugs or other factors (e.g., delayed or inadequate treatment, suboptimal observation of drug intake) as major determinants of death needs further evaluation. The appearance of XDR TB in western Europe confirms that poor management and poor infection control in congregate settings exist and that new rapid diagnostic tests and new drugs are urgently needed.

Medical and surgical management of otitis media

At the dawn of the new millennium, we have seen a vigorous clinical response to the changing and challenging problems of otitis media, with a high prevalence, greater bacterial resistance, and even greater educational and occupational impact than previously realized. New medical and surgical treatments and a better understanding of host-disease factors, including genetic and molecular investigations, may emerge from this productive year’s work. This update summarizes the latest epidemiologic and basic science studies, new medications, management of multidrug resistance by changing indications for antibiotic use and dosing regimens, the new pneumococcal vaccine, and the role of laser myringotomy.