A few examples will illustrate the impact of the emergence of drug-resistant organisms and their selection by the wide spread use of antimicrobial drugs.

Gonococci

When sulfonamides were first used in the late 1930s for the treatment of gonorrhea, virtually all isolates of gonococci were susceptible, and most infections were cured. A few years later, most strains had become resistant to sulfonamides, and gonorrhea was rarely curable by these drugs. Most gonococci were still highly susceptible to penicillin. Over the next decades, there was a gradual increase in resistance to penicillin, but large doses of that drug were still curative. In the 1970s, β-lactamase-producing gonococci appeared, first in the Philippines and in West Africa, and then spread to form endemic foci worldwide. Such infections could not be treated effectively by penicillin but were treated with spectinomycin. Resistance to spectinomycin has appeared. Third-generation cephalosporins or quinolones were recommended to treat gonorrhea. However, the emergence of quinolone resistance in some geographic locations has subsequently limited their use, and they are no longer recommended as first-line treatment. Of more concern are the recent observations regarding treatment failures with oral third-generation cephalosporins due to rising MICs among N. gonorrhoeae. Parenteral third generation cephalosporins remain the agents of choice for gonorrhea. However, in cases of apparent relapse, cultures for N. gonorrhoeae followed by susceptibility testing are recommended to monitor the trend of emerging cephalosporin resistance.

Meningococci

Until 1962, meningococci were uniformly susceptible to sulfonamides, and these drugs were effective for both pro phylaxis and therapy. Subsequently, sulfonamide-resistant meningococci spread widely, and the sulfonamides have now lost their usefulness against meningococcal infections. Penicillins remain effective for therapy, and until recently, rifampin was used for prophylaxis. However, rifampin-resistant meningococci have emerged (as high as 27% of isolates), which may cause invasive infections. Fluoroquinolones have largely replaced rifampin for prophylaxis.

Staphylococci

In 1944, most staphylococci were susceptible to penicillin G, although a few resistant strains had been observed. After massive use of penicillin, 65–85% of staphylococci isolated from hospitals in 1948 were β-lactamase producers and thus resistant to penicillin G. The advent of β-lactamase-resistant penicillins (eg, nafcillin, methicillin, and oxacillin) provided a temporary respite, but infections caused by methicillin resistant S. aureus (MRSA) are common. Presently, penicillin- resistant staphylococci include not only those acquired in hospitals but also 80–90% of those isolated in the community. These organisms also tend to be resistant to other drugs (eg, tetracyclines). Likewise, MRSA are common in both community-onset infections caused by circulating clones such as USA 300 and in hospital-acquired infections. Health care-associated infections may be caused by either the more susceptible community strains or the typical multidrug resistant nosocomially acquired clones. Vancomycin has been the major drug used for treatment of MRSA infections, but recovery of isolates with intermediate resistance and the reports of several cases of high-level resistance to vancomycin have spurred the search for newer agents. Some of the newer agents with activity against MRSA include daptomycin; line zolid; quinupristin–dalfopristin; and a novel cephalosporin agent, ceftaroline.

Pneumococci

S. pneumoniae was uniformly susceptible to penicillin G until 1963, when relatively penicillin-resistant strains were found in New Guinea. Penicillin-resistant pneumococci subsequently were found in South Africa, Japan, Spain, and later worldwide. In the United States, approximately 10% of pneumococci are resistant to penicillin G (minimum inhibitory concentrations [MICs] > 2 μg/mL), and approximately 18% are intermediate (MICs, 0.1–1 μg/mL). The penicillin resistance is attributable to altered PBPs. Penicillin resistance in pneumococci tends to be clonal. Pneumococci also are frequently resistant to trimethoprim–sulfamethoxazole, erythromycin, and tetracycline. Quinolone resistance is also beginning to emerge because of increased usage and is caused by mutations in DNA topoisomerase IV or GyrA or GyrB of DNA gyrase.

Enterococci

The enterococci have intrinsic resistance to multiple anti microbials, including penicillin G and ampicillin with high MICs, cephalosporins with very high MICs, low level resistance to aminoglycosides, and resistance to trimethoprim–sulfamethoxazole in vivo. The enterococci also have shown acquired resistance to almost all other antimicrobials as follows: altered PBPs and resistance to β-lactams; high-level resistance to aminoglycosides; and resistance to fluoroquinolones, macrolides, azalides, and tetracyclines. Some enterococci have acquired a plasmid that encodes for β-lactamase that renders them fully resistant to penicillin and ampicillin. Of greatest importance is the development of resistance to vancomycin, which has become common in Europe and North America, although there is geographic variation in the percentages of enterococci that are vancomycin resistant. Enterococcus faecium is the species that is most commonly vancomycin resistant. In outbreaks of infections caused by vancomycin-resistant enterococci (VRE), the isolates may be clonal or genetically diverse. Resistance to the streptogramins (quinupristindalfopristin) also occurs in enterococci. Increasing resistance to active drugs for VRE treatment such as linezolid is of major concern.

Gram-Negative Enteric Bacteria

Most drug resistance in enteric bacteria is attributable to the widespread transmission of resistance plasmids among different genera. About half the strains of Shigella species in many parts of the world are now resistant to multiple drugs.

Salmonellae carried by animals have also developed resistance, particularly to drugs (especially tetracyclines) incorporated into animal feeds. The practice of incorporating drugs into animal feeds causes farm animals to grow more rapidly but is associated with an increase in drug-resistant enteric organisms in the fecal microbiota of farm workers. A concomitant rise in drug-resistant Salmonella infections in Britain led to a restriction on antibiotic supplements in ani mal feeds. Continued use of tetracycline supplements in ani mal feeds in the United States may contribute to the spread of resistance plasmids and drug-resistant salmonellae. In the late 1990s, a clone of Salmonella serotype Typhimurium phage type DT104 emerged and spread globally. This particular strain is resistant to ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline.

Plasmids carrying drug resistance genes occur in many Gram-negative bacteria of the normal gut microbiota. The abundant use of antimicrobial drugs—particularly in hospitalized patients—leads to the suppression of drug-susceptible organisms in the gut microbiota and favors the persistence and growth of drug-resistant bacteria, including Enterobacter, Klebsiella, Proteus, Pseudomonas, and Serratia species and fungi. Such organisms present particularly difficult problems in granulocytopenic and immunocompromised patients. The closed environments of hospitals favor transmission of such resistant organisms through personnel and fomites as well as by direct contact.

Mycobacterium tuberculosis

Primary drug resistance in M. tuberculosis occurs in about 10% of isolates and most commonly is to INH or streptomycin. Resistance to rifampin or ethambutol is less common. INH and rifampin are the primary drugs used in most standard treatment regimens; other first-line drugs are pyrazinamide and ethambutol. Resistance to INH and rifampin is considered multiple drug resistance. In the United States, multiple drug resistance of M. tuberculosis (MDR-TB) has significantly decreased. Worldwide, the highest rates of MDR-TB have been reported from Eastern European countries, particularly among countries of the former Soviet Union. Poor compliance with drug treatment is a major factor in the development of drug resistance during therapy. Control of MDR-TB is a significant worldwide problem. More recently, emergence of extensively drug-resistant TB (XDR-TB) presents a significant challenge to global tuberculosis control. In addition to resistance to INH and rifampin, these organisms are also resistant to quinolones and injectable drugs, such as aminoglycosides or capreomycin (second-line agents).

اخر الاخبار

اخبار العتبة العباسية المقدسة

وزارة التعليم العالي تكرم جامعة العميد لحصولها على جائزة المكتبة الأكاديمية المتميزة

جمعية العميد تناقش استعداداتها لانطلاق فعاليات المؤتمر العلمي الرابع لإحياء تراث أمير المؤمنين (عليه السلام)

أكاديمية التطوير الإداري تواصل برنامج الخطة الخمسينية لعدد من ملاكات العتبة العباسية المقدسة

المجمع العلمي يواصل تقديم دورته التطويرية لعدد من الملاكات التربوية في الديوانية

المزيد

الآخبار الصحية

الرياضة وحدها لا تكفي.. كيف يؤثر الجلوس الطويل على الصحة؟

دراسة: بدائل السكر ليست آمنة على الكبد

تفاحة قبل النوم.. عادة بسيطة مفيدة أم خطر على الصحة؟

احذر مشاركتها مع الآخرين.. 3 أدوات شائعة قد تنقل أمراض خطيرة

المزيد

الآخبار التكنلوجية

الهنغاري لاسلو كراسناهوركاي يفوز بجائزة نوبل للآداب 2025

رسميا.. إعلان الفائز بجائزة نوبل للسلام لعام 2025

باحثون: تشات جي بي تي ونماذج الذكاء الاصطناعي يمكن "تسميمها"

عالمان في الأعصاب يرفعان دعوى قضائية ضد شركة آبل

المزيد

مواضيع ذات صلة

Antimicrobial Chemoprophylaxis

Drug–Pathogen Relationships

Measurement of Antimicrobial Activity

Origin of drug resistance

Resistance to Sulfonamide

Control of Antibiotics Overuse

International Distribution of Antibiotics: A Scandinavian Example

Rediscovery of Penicillin by a Basic Scientific Approach

Penicillin: the First Antibiotic

Sulfonamide: the First Antibacterial Agent Acting Selectively

Drug elimination

Drug distribution