Antimicrobial Era Research Articles

Origin of Antimicrobial Therapy.

Medical historians typically situate the origins of the antimicrobial era during the early germ period at the turn of the 20th century. They have regarded the development of chemical compounds designed to treat infectious diseases by killing their causative germ as the beginning of the antimicrobial era. Scholars, however, had been speculating about the causal relationship between germs and diseases for centuries beforehand. One of them also addressed the practical applications of this theory. The Italian physician Fracastoro proposed in 1546 that infectious diseases could be treated by administering substances to antagonize disease causing germs. He claimed that health could be restored to people who became ill with infections by nullifying the responsible germs at a time when investigators could not see germs or investigate their ability to cause disease. The long genealogy of antimicrobial therapy from its conception to its fruition took place over the span of several centuries.

Septic arthritis in the antimicrobial stewardship era

Septic arthritis in the antimicrobial stewardship era

Carbapenem-Resistant Enterobacterales: Considerations for Treatment in the Era of New Antimicrobials and Evolving Enzymology.

Purpose of ReviewGram-negative resistance is a growing concern globally. Enterobacterales, formerly Enterobacteriaceae, have developed resistance mechanisms to carbapenems that leave very few antimicrobial options in the clinician’s armamentarium.Recent FindingsNew antimicrobials like ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol, and plazomicin have the potential to overcome resistance mechanisms in Enterobacterales including different classes of carbapenemases.SummaryNovel β-lactam/β-lactamase inhibitors, plazomicin, and cefiderocol give the clinician options that were once not available. Utilizing these options is of the utmost importance when treating carbapenem-resistant Enterobacterales.

Mortality pattern among tuberculosis patients on treatment in Nigeria: A systematic review and meta-analysis

Background: Tuberculosis (TB) has continued to be associated with a substantial number of deaths, even in the era of effective antimicrobials. Nigeria is one of the countries with a high tuberculosis burden and has sub-optimal documentation of TB related deaths. Vital statistics/registration is not robust, and mortality surveys are rarely undertaken. In this study, we aimed to determine a precise estimate of TB related deaths on treatment and the trends in death rate while on TB treatment in Nigeria. Methods: We searched electronic databases for eligible studies from 1st January 2000 to 31st December 2017. We generated pooled death rate estimates using random-effects models and determined trends using meta-regression. Results: We identified 546 studies, of which 28 fulfilled the criteria for quantitative analysis. Overall, studies reported on 64,999 individuals. The pooled TB death rate during treatment was 6.6% (95% CI; 5.2-8.1%). There was a non-significant rise in TB related deaths on treatment of 0.2% per year (p-value = 0.454). Conclusion: We found a low TB related deaths on treatment, death rate and slight temporal rise over the study years. There is a need for continuous vital registration, including TB related death, and mortality survey among TB patients.

Distribution of carbapenemase genes in clinical isolates of Acinetobacter baumannii & a comparison of MALDI-TOF mass spectrometry-based detection of carbapenemase production with other phenotypic methods

Background & objectives:Carbapenemase-producing Acinetobacter baumannii (CRAB) poses a continuous threat to the current antimicrobial era with its alarming spread in critical care settings. The present study was conducted to evaluate the diagnostic potential of phenotypic methods for carbapenemase [carbapenem-hydrolyzing class D β-lactamases (CHDLs) and metallo-β-lactamases (MBLs)] production, by comparing with molecular detection of genes.Methods:One hundred and fifty clinical CRAB isolates collected between August 2013 and January 2014 were studied. Multiplex PCR was performed to identify the carbapenemases produced (class D blaOXA-51, blaOXA-23, blaOXA-48, blaOXA-58; class B blaVIM, blaNDM-1, blaIMP; class A blaKPC). Each isolate was evaluated for carbapenemase production by studying the pattern of imipenem hydrolysis using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS).Results:The most commonly encountered carbapenemase genes were blaOXA-51 (100%), blaOXA-23 (98%), blaVIM (49.3%), blaNDM-1 (18.7%) and blaOXA-58 (2%). MALDI-TOF MS was able to detect 30.6 per cent carbapenemases within three hours (P=0.001 for MBL and P>0.05 for CHDL) and 65.3 per cent within six hours (P=0.001 for MBL and P>0.05 for CHDL).Interpretation & conclusions:MALDI-TOF MS reliably detected carbapenemase activity within a short span of time, thus helping in tailoring patient therapy. MALDI-TOF MS, once optimized, can prove to be a useful tool for timely detection of carbapenemase production by A. baumannii and consequently in directing appropriate antimicrobial therapy.

Mini Review on Antimicrobial Peptides, Sources, Mechanism and Recent Applications.

Antimicrobial peptides in recent years have gained increased interest among scientists, health professionals and the pharmaceutical companies owing to their therapeutic potential. These are low molecular weight proteins with broad range antimicrobial and immuno modulatory activities against infectious bacteria (Gram positive and Gram negative), viruses and fungi. Inability of micro-organisms to develop resistance against most of the antimicrobial peptide has made them as an efficient product which can greatly impact the new era of antimicrobials. In addition to this these peptides also demonstrates increased efficacy, high specificity, decreased drug interaction, low toxicity, biological diversity and direct attacking properties. Pharmaceutical industries are therefore conducting appropriate clinical trials to develop these peptides as potential therapeutic drugs. More than 60 peptide drugs have already reached the market and several hundreds of novel therapeutic peptides are in preclinical and clinical development. Rational designing can be used further to modify the chemical and physical properties of existing peptides. This mini review will discuss the sources, mechanism and recent therapeutic applications of antimicrobial peptides in treatment of infectious diseases.

Lemierre's syndrome: A re-emerging infection.

Lemierre’s syndrome (LS) or suppurative thrombophlebitis of the jugular vein most often arises as a complication of head and neck infections. LS was more common before the antimicrobial era but the incidence decreased during the 1960s with increased use of penicillin for bacterial throat infections. However, the incidence is now increasing. Though the protean manifestations make recognition difficult, a recent history of sore throat and septic emboli in the lungs should prompt consideration of LS.

Trichomonas vaginalis infection and prostate-specific antigen concentration: Insights into prostate involvement and prostate disease risk.

The protist Trichomonas vaginalis causes a common, sexually transmitted infection and has been proposed to contribute to the development of chronic prostate conditions, including benign prostatic hyperplasia and prostate cancer. However, few studies have investigated the extent to which it involves the prostate in the current antimicrobial era. We addressed this question by investigating the relation between T. vaginalis antibody serostatus and serum prostate-specific antigen (PSA) concentration, a marker of prostate infection, inflammation, and/or cell damage, in young, male, US military members. We measured T. vaginalis serum IgG antibodies and serum total PSA concentration in a random sample of 732 young, male US active duty military members. Associations between T. vaginalis serostatus and PSA were investigated by linear regression. Of the 732 participants, 341 (46.6%) had a low T. vaginalis seropositive score and 198 (27.0%) had a high score, with the remainder seronegative. No significant differences were observed in the distribution of PSA by T. vaginalis serostatus. However, slightly greater, nonsignificant differences were observed when men with high T. vaginalis seropositive scores were compared with seronegative men, and when higher PSA concentrations were examined (≥0.70 ng/mL). Specifically, 42.5% of men with high seropositive scores had a PSA concentration greater than or equal to 0.70 ng/mL compared with 33.2% of seronegative men (adjusted P = .125). Overall, our findings do not provide strong support for prostate involvement during T. vaginalis infection, although our suggestive positive findings for higher PSA concentrations do not rule out this possibility entirely. These suggestive findings may be relevant for prostate condition development because higher early- to mid-life PSA concentrations have been found to predict greater prostate cancer risk later in life.

The Diagnostic Yield, Safety, and Impact of Flexible Bronchoscopy in Non-HIV Immunocompromised Critically Ill Patients in the Intensive Care Unit.

BackgroundFlexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) have major roles in the evaluation of parenchymal lung diseases in immunocompromised patients. Given the limited evidence, lack of standardized practice, and variable perception of procedural safety, uncertainty still exists on what constitutes the best approach in critically ill patients with immunocompromised state who present with pulmonary infiltrates in the era of prophylactic antimicrobials and the presence of new diagnostic tests.ObjectiveTo evaluate the diagnostic yield, safety and impact of FB and BAL on management decisions in immunocompromised critically ill patients admitted to the intensive care unit (ICU).MethodsA prospective, observational study of 106 non-HIV immunocompromised patients admitted to the intensive care unit with pulmonary infiltrates who underwent FB with BAL.ResultsFB and BAL established the diagnosis in 38 (33%) of cases, and had a positive impact on management in 44 (38.3%) of cases. Escalation of ventilator support was not required in 94 (81.7%) of cases, while 18 (15.7%) required invasive and 3 (2.6%) required non-invasive positive pressure ventilation after the procedure. Three patients (2.6%) died within 24 h of bronchoscopy, and 46 patients (40%) died in ICU. Significant hypoxemia developed in 5% of cases.ConclusionFB can be safely performed in immunocompromised critically ill patients in the ICU. The yield can be improved when FB is done prior to initiation of empiric antimicrobials, within 24 h of admission to the ICU, and in patients with focal disease.

Endophthalmitis: Then and Now

To report historically evolving strategies (then and now) in prevention and management of endophthalmitis. A perspective on relevant topics in the prophylaxis and management of endophthalmitis. This is an author-selected review of studies leading to changes in strategies for endophthalmitis management over the last 100 years. The current perspective discusses the trends and strategies over the past century. Historically, 3 endophthalmitis time-periods have existed and include the pre-antimicrobial era, the predominantly systemic antimicrobial era, and the current intravitreal antimicrobial era. The management of endophthalmitis from different etiologies, including endogenous, postinjection, post-cataract surgery, and other anterior segment-related (eg, post-penetrating keratoplasty), bleb-associated, glaucoma drainage device-associated, and open globe injury-associated, are discussed. Specific etiologies may predict most common microbial causes and may guide differing management strategies. Pars plana vitrectomy offers theoretical advantages but is generally reserved for patients with more advanced disease. Despite advances over the past 100 years, endophthalmitis is an important sight-threatening complication. Timely management with the appropriate use of antimicrobial agents may optimize visual outcomes.

Hostage to History: The Duration of Antimicrobial Treatment for Acute Streptococcal Pharyngitis.

Oral antimicrobial treatment of acute streptococcal pharyngitis commonly is given for 10 days. An investigation was conducted of journal publications and textbooks from the dawn of the antimicrobial era to the present in order to discover the basis for this settled practice. Current treatment duration for acute streptococcal pharyngitis was established half a century ago under conditions significantly different from those currently encountered by the average clinician. The 10-day treatment standard evolved without scientific justification. There have been no therapeutic trials that have validated the necessity for 10 days of oral antimicrobial treatment. Yet, despite the lack of a scientific foundation, the rarity of acute rheumatic fever in developed countries, the high failure rate for streptococcal eradication and evidence that short-course therapy with a nonpenicillin antimicrobial yields equivalent eradication rates, the 10-day rule persists because of long clinical usage and the inherent power of the number 10. Efforts to change this clinical benchmark will likely meet with resistance from practicing physicians.

Effects of In-Feed Chlortetracycline Prophylaxis in Beef Cattle on Animal Health and Antimicrobial-Resistant Escherichia coli.

The occurrence of human bacterial infections resistant to antimicrobial therapy has been increasing. It has been postulated that antimicrobial resistance was inevitable, but the life span of the antimicrobial era has been prematurely compromised due to the misuse of antimicrobials in clinical and agricultural practices. Direct evidence relating the use of antimicrobials in livestock production to diminished human health outcomes due to antimicrobial resistance is lacking, and the U.S. Food and Drug Administration has taken an approach to maximize therapeutic efficacy and minimize the selection of resistant microorganisms through judicious use of antimicrobials. This study demonstrated that prophylactic in-feed treatment of chlortetracycline administered for 5 days to calves entering feedlots is judicious, as this therapy reduced animal morbidity, reduced the use of antimicrobials more critical to human health, and had no long-term impact on the occurrence of antimicrobial-resistant E. coli.

Era of Antimicrobials: Winning Microbes!

Era of Antimicrobials: Winning Microbes!

Era of Antimicrobials: Winning Microbes!

Era of Antimicrobials: Winning Microbes!

Community-acquired lobar pneumonia encountered at autopsy

A 72-year-old woman 12 years status-post partial mastectomy, adjuvant radiation, and five years of anastrozole for stage I estrogen receptor/progesterone receptor positive breast adenocarcinoma presented with neck pain. MRI showed extensive metastatic disease involving the skull and the vertebral bodies of the cervical and thoracic spine. She was started on dexamethasone. Bone scan revealed multiple sites of disease, including the ribs, spine, and pelvis. Four weeks following initiation of radiation to the cervical spine for palliation of neurologic symptoms, the patient exhibited a few days of fever at home, without respiratory distress, and died in her sleep. The patient did not have any documented pneumococcal vaccination. At autopsy, dense lobar consolidation with red hepatization was found in the entire lower lobe of the left lung (Fig. 1). On microscopic examination, the alveolar spaces were completely filled with fibrin and scattered neutrophilic leukocytes (Fig. 2). Gram stain revealed multiple lancet-shaped Gram positive diplococci in pairs, consistent with Streptococcus pneumoniae (Fig. 3). Additionally, several bones contained metastatic ER positive adenocarcinoma (not shown). The cause of death was typical community-acquired lobar pneumonia with respiratory failure in the setting of widely metastatic breast cancer. In the era of modern antimicrobials and polyvalent vaccination, S. pneumoniae accounts for approximately 10–15% of cases of community-acquired pneumonia, and is attended by a 10–12% 30-day mortality rate.

Antimicrobial stewardship to optimize antimicrobial use

Antimicrobials can be viewed as double edged sword. Their life saving benefits and disease modifying effects are widely known and appreciated. However, the opposing edge of the sword can be just as sharp, which can cause serious patient harm in the form of adverse drug events and emergence of resistance. While the adverse events can occur during therapy and are more tangible to the practicing clinicians, the emergence of resistance often occurs late and is less obvious. In 1956, a noted microbiologist Ernest Jawetz once wrote, “On the whole, the position of antimicrobial agents in medical therapy is highly satisfactory. The majority of bacterial infections can be cured simply, effectively and cheaply. The mortality and morbidity from bacterial diseases has fallen so low that they are no longer among the important unsolved problems in modern medicine(1).”In the current antimicrobial era some 50 plus years, after these optimistic observations were made, shows an increase in number of infections that are difficult to treat, leading to an increase in morbidity and mortality. Studies have shown a strong relationship between antibiotic use and selection of resistance in humans. Controlled studies have also shown in which patients with prior use of antimicrobials were more likely to be colonized or infected with resistant bacteria. A number of infectious diseases remain as unsolved problems in modern medicine. This has become a challenge to many clinicians calling attention to the abuse of antibiotics and its results(2,3)

Pseudomonas in augmented care: should we worry?

The problem of Pseudomonas as a nosocomial pathogen is not new, with some authors dating its onset to the start of the antimicrobial era, although other factors, such as the growth of intensive or augmented care, have a part to play. This paper outlines the historical and environmental issues that may be associated with a potential increase in the incidence of this difficult-to-treat pathogen.

What's new on the antimicrobial horizon?

The antimicrobial era is threatened by high levels of antibiotic resistance, the limited number and disparate availability of effective antibiotics against diverse bacterial species, and reduced involvement by the pharmaceutical industry in the development of new anti-infectives. For the treatment of resistant Gram-positive coccal infections, particularly methicillin-resistant staphylococcal infections, vancomycin has long been the mainstay antimicrobial agent due to its safety, durability against resistance, and lack of other approved alternatives. However, the efficacy and safety of vancomycin for the treatment of many serious infections has been called into question. Promising results from clinical trials suggest that five new antimicrobials could offer safe and effective alternatives to vancomycin. With regard to resistant Gram-negative infections, new carbapenems and some other options will be available. This paper reviews the safety and efficacy of these new antimicrobial agents against resistant bacterial pathogens.

Daptomycin and tigecycline: a review of clinical efficacy in the antimicrobial era

There is a clinical need for new treatment options as a result of continued increase in the expression of resistance among bacterial pathogens. A number of compounds currently in development show promise. However, in some cases, there is concern that resistance may develop quickly to new compounds that are based on existing antimicrobial agents. Therefore, daptomycin, a novel lipopeptide with a unique mode of action, is of particular interest. It has rapid bactericidal activity against growing and stationary-phase bacteria, once-daily dosing regimen, and has a low potential for the development of resistance. It has been approved for the treatment of complicated skin and soft tissue infections caused by Gram-positive bacteria, and registration for treatment of infective endocarditis and bacteraemia is anticipated. Daptomycin is a welcome addition to the antimicrobial armamentarium for the treatment of bacterial infections. Tigecycline is a new glycyclcycline antimicrobial recently approved for use in the USA, Europe and elsewhere. While related to the tetracyclines, tigecycline overcomes many of the mechanisms responsible for resistance to this class. It is a novel broad spectrum glycylcycline with good activity against Gram-positive, many Gram-negative, anaerobic, and some atypical pathogens that has been developed to address this need. It is efficacious in complicated skin and soft tissue infections and in intra-abdominal infections. This review aims to summarise the key clinical data of daptomycin and tigecycline which hold promise for widespread clinical use in the next decade.

Lemierre Syndrome

Lemierre syndrome is a condition that can have high morbidity and mortality, but if it is diagnosed early in a patient's workup, that is, in the ED, the morbidity and mortality can be significantly decreased. First described by Dr Andre Lemierre in 1936, Lemierre syndrome is a clinical condition, which presents as septic emboli in the internal jugular vein after an untreated pharyngitis. This condition can have significant morbidity and mortality; therefore, although it is not common in today's era of antimicrobials, it should still be considered and thought of to prevent the significant consequences that may occur from it. In this article, we will present a child who was admitted for fever, neck pain, lymphadenopathy, and lung abscesses which was diagnosed as Lemierre syndrome. This syndrome will be discussed so as to heighten clinical awareness of it.