Molecular basis of group A streptococcal virulence.

The group A streptococcus (GAS) (Streptococcus pyogenes) is among the most common and versatile of human pathogens. It is responsible for a wide spectrum of human diseases, ranging from trivial to lethal. The advent of modern techniques of molecular biology has taught much about the organism's virulence, and the genomes of several GAS types have now been deciphered. Surface structures of GAS including a family of M proteins, the hyaluronic acid capsule, and fibronectin-binding proteins, allow the organism to adhere to, colonise, and invade human skin and mucus membranes under varying environmental conditions. M protein binds to complement control factors and other host proteins to prevent activation of the alternate complement pathway and thus evade phagocytosis and killing by polymorphonuclear leucocytes. Extracellular toxins, including superantigenic streptococcal pyrogenic exotoxins, contribute to tissue invasion and initiate the cytokine storm felt responsible for illnesses such as necrotising fasciitis and the highly lethal streptococcal toxic shock syndrome. Progress has been made in understanding the molecular epidemiology of acute rheumatic fever but less is understood about its basic pathogenesis. The improved understanding of GAS genetic regulation, structure, and function has opened exciting possibilities for developing safe and effective GAS vaccines. Studies directed towards achieving this long-sought goal are being aggressively pursued.

Acute pharyngitis.

The primary care physician needs to identify those patients with acute pharyngitis who require specific antimicrobial therapy and to avoid unnecessary and potentially deleterious treatment in the large majority of patients who have a benign, self-limited infection that is usually viral. In most cases, differentiating between these two types of infection can be accomplished easily if the physician considers the epidemiologic setting, the history, and the physical findings, plus the results of a few readily available laboratory tests. When antimicrobial therapy is required, the safest, narrowest-spectrum, and most cost-effective drugs should be used. Despite agreement on these principles by expert advisory committees, data from national surveys of ambulatory care indicate that antimicrobial agents continue to be prescribed indiscriminately for upper respiratory infections.

The initial outpatient-physician encounter in group A streptococcal necrotizing fasciitis.

Of 15 patients in whom the diagnosis of streptococcal necrotizing fasciitis was missed at initial outpatient evaluation, 8 died. Although influenza-like and gastrointestinal symptoms were common, the most consistent clinical clue was unrelenting pain out of proportion to the physical findings. Necrotizing fasciitis should be considered in patients presenting with the latter complaint, even if there is only mild or no fever or erythema.

Murine model of recurrent group G streptococcal cellulitis: no evidence of protective immunity.

Despite the well-known tendency of cellulitis due to beta-hemolytic streptococci to recur, little is known regarding the mechanisms of human immunity to this infection. We established cellulitis in mice by using a strain of group G streptococcus (1750) originally isolated from the bloodstream of a patient with acute cellulitis. This strain, which has been studied extensively in our laboratory, expresses M protein structurally and functionally analogous to that of group A streptococci, and we have cloned and sequenced the gene encoding this protein (emmMG1). Mice injected with 5 x 10(7) CFU of strain 1750 developed nonlethal necrotic skin and soft tissue infections that healed spontaneously after 14 to 16 days. After healing, the mice were repetitively reinoculated three times with the same challenge dose of 1750. Lesion size did not decrease in severity, size, or time to healing after repetitive challenge. The maximum lesion size and tissue concentration of microorganisms increased between the first and fourth challenges. Pretreatment of 1750 cells with opsonic antisera to MG1 diminished neither the maximum lesion size nor the time course of evolution of the lesions. Thus, in the mouse model used here, there was no evidence of acquired protective immunity to experimentally induced cellulitis.

Diagnosis and management of group A streptococcal pharyngitis: a practice guideline. Infectious Diseases Society of America.

This is the second in a series of practice guidelines commissioned by the Infectious Diseases Society of America through its Practice Guidelines Committee. The purpose of these guidelines is to provide assistance to clinicians when making decisions on treating the conditions specified in each guideline. The targeted providers are pediatricians, family practitioners, and internists. The targeted patients and setting for the acute pharyngitis guideline are pediatric, adolescent, and adult outpatients with a complaint of sore throat. Funding was provided by the IDSA. Panel members represented experts in adult and pediatric infectious diseases. The guidelines are evidence-based. A standard ranking system was used for the strength of the recommendations and the quality of the evidence cited in the literature reviewed. The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council. An executive summary, algorithms, and tables highlight the major recommendations. Indicators of quality will assist in guideline implementation. The guideline will be listed on the IDSA home page at http://www.idsociety.org.

M proteins of group C streptococci isolated from patients with acute pharyngitis.

We studied 15 strains of group C (Streptococcus equi subsp. equisimilis) [corrected] isolated from the throats of college students with acute pharyngitis and 5 strains isolated from patients with noninfectious problems. Nineteen of the 20 strains resisted phagocytic killing during incubation in normal human blood, suggesting that they might express M proteins. Genomic DNA from all 20 strains hybridized with a probe corresponding to the carboxyterminal one-third of the group A M-protein gene emm24, a region that is highly conserved among M proteins of group A and group G streptococci. The DNA sequences of the N-terminal (variable) regions of the M-protein-encoding genes from two disease-associated group C isolates and one control isolate were determined. The predicted amino acid sequences of the two pharyngitis strains were identical and were 88% homologous to the amino acid sequence of a group G M-protein gene. The predicted terminal amino acid sequence of the control strain does not correspond to any such sequences in the GenBank database. All three strains studied possess the conserved region domain common to class I group A M-protein types epidemiologically associated with rheumatic fever. These studies demonstrate the presence of M proteins in strains of S. equi subsp. equisimilis [corrected] isolated in cases of endemically occurring acute pharyngitis. Certain of these proteins are similar to those of group G streptococci, while others may represent new M types. The similarity in structure and function between M proteins of nonrheumatogenic serogroups and those of rheumatogenic group A streptococci suggests that factors other than or in addition to M protein per se are likely involved in the pathogenesis of rheumatic fever.

Identification of a fibronectin-binding protein (GfbA) in pathogenic group G streptococci.

Attachment to eukaryotic cell surfaces is an essential step in the establishment of colonization and infection by bacterial pathogens. This report examines the adherence capabilities of pathogenic group G streptococci and demonstrates that certain group G streptococcal clinical isolates express a fibronectin-binding protein. This protein, termed GfbA for group G streptococcal fibronectin-binding protein, mediates adherence to human skin fibroblasts (HSF). The gene encoding this protein, gfbA, was isolated, and the complete DNA sequence of gfbA was determined. From this sequence GfbA was predicted to be a 580-amino-acid protein (molecular weight = 64,979) with significant amino acid identity to the group A streptococcal fibronectin-binding proteins SfbI and protein F (PrtF) (76 and 78% identity, respectively). GfbA contains regions with notable identity to the fibronectin-binding repeat domains of PrtF. gfbA(+) strains were able to bind to HSF, and preincubation of the gfbA(+) strains with fibronectin blocked this adherence. In addition, gfbA(+) strains were able to bind radiolabeled fibronectin, and this binding was inhibited with addition of excess unlabeled fibronectin. gfbA-negative strains were not able to bind either the HSF or radiolabeled fibronectin. DNA homologous to gfbA was found in 36% of the group G streptococcal isolates examined. Since not all group G streptococcal strains examined contained gfbA, this suggests there might be other tissue-specific adherence molecules expressed by these pathogenic strains.

Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci, and HACEK microorganisms. American Heart Association.

OBJECTIVE: To provide guidelines for the treatment of endocarditis in adults caused by the following microorganisms: viridans streptococci and other streptococci, enterococci, staphylococci, and fastidious gram-negative bacilli of the HACEK group. PARTICIPANTS: An ad hoc writing group appointed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young. EVIDENCE: Published studies of the treatment of patients with endocarditis and the collective clinical experience of this group of experts. CONSENSUS PROCESS: The recommendations were formulated during meetings of the working group and were prepared by a writing committee after the group had agreed on the specific therapeutic regimens. The consensus statement was subsequently reviewed by standing committees of the American Heart Association and by a group of experts not affiliated with the working group. CONCLUSIONS: Sufficient evidence has been published that recommendations regarding treatment of the most common microbiological causes of endocarditis (viridans streptococci, enterococci, Streptococcus bovis, staphylococci, and the HACEK organisms) are justified. There are insufficient published data to make a strong statement regarding the efficacy of specific therapeutic regimens for cases of endocarditis due to microorganisms that uncommonly cause endocarditis. As a useful aid to the practicing clinician, the writing group developed a consensus opinion regarding management of endocarditis caused by the most commonly encountered microorganisms and regarding those cases due to infrequent causes of endocarditis.

Molecular aspects of bacterial colonization.

Bacteria have developed a wide variety of molecular mechanisms that permit firm adherence to a biologic surface. This review summarizes basic principles involved in this process, as exemplified by adherence of the group A streptococcus to oral epithelium, staphylococci to indwelling prostheses, and Escherichia coli to uroepithelium and enterocytes.

Antimicrobial prophylaxis of infection.

Antimicrobial agents are used to prevent infections in a variety of clinical circumstances. In certain instances, the precise indications for prophylaxis remain controversial, and the preferred regimens undergo alterations based upon evolving clinical experience, changing patterns of microbial susceptibility, and innovations in medical and surgical practice. This article outlines the general principles underlying the use of antimicrobial prophylaxis and presents recommendations for the use of such prophylaxis in three areas: (1) surgery involving contaminated, clean-contaminated, and clean procedures; (2) prevention of infections due to specific pathogens, including Neisseria meningitidis, Hemophilus influenzae, Streptococcus pneumoniae, and Streptococcus pyogenes; and (3) prevention of infective endocarditis.

M proteins of group G streptococci: mechanisms of resistance to phagocytosis.

Group G streptococci that express M protein and resist phagocytosis in human blood (virulent strains) were compared with strains of groups G and A that are readily phagocytosed (avirulent). Virulent group G streptococci were less effective (P < .05) as activators of the alternative complement pathway (ACP) than were avirulent streptococci. In immunofluorescence studies, C3 bound more avidly to avirulent than to virulent group G streptococci. Resistance of virulent group G strains to ACP opsonization and to phagocytosis was markedly diminished by removal with pepsin of the type-specific portion of the M molecule. Preincubation with fibrinogen did not diminish ACP activation or C3 binding by virulent group G and A streptococci but did exert an antiphagocytic effect. Given the similarity of M proteins of groups G and A in structure and function, other microbial constituents are likely responsible for differences in the spectra of illnesses attributable to the two serogroups.

Infections associated with prosthetic devices: clinical considerations.

The successful development of synthetic materials and introduction of artificial devices into nearly all body systems has been shadowed by the adaptation of microorganisms to the opportunities these devices afford for eluding defenses and invading the host. Clinicians are faced with the task of recognizing the manifestations of device-associated infection, predicting the likely pathogens involved, knowing the appropriate diagnostic methods, and initiating appropriate therapy. Infections associated with prosthetic heart valves are particularly challenging to successfully treat; surgical replacement may be necessary. Infection associated with an artificial joint usually requires removal of the device in addition to appropriate antibiotics. Intravascular associated infections are the leading cause of nosocomial bacteremias and, because of their intravascular location, these infections are often life catheter threatening if not promptly diagnosed and treated. Even contact lenses, external to epithelial surfaces, may give rise to serious sight-threatening infections. Although artificial devices play a paramount role in medicine today, infection is an ever present potential with which clinicians must be familiar.

Absence of HIV transmission from an infected dentist to his patients. An epidemiologic and DNA sequence analysis.

OBJECTIVE: To determine if a general dentist with human immunodeficiency virus (HIV) infection transmitted HIV to any of his patients. DESIGN: A cohort study in which all patients treated by a dentist who developed the acquired immunodeficiency syndrome (AIDS) were identified and attempts were made to contact all patients for HIV antibody testing. SETTING: A general dentistry clinic operated by the Department of Veterans Affairs in southeastern Florida. PARTICIPANTS: All patients treated by a dentist during the 5 3/4 years before he developed AIDS were identified in a computerized registry of dental care. MAIN OUTCOME MEASURES: Attempts were made to contact all living patients for counseling and HIV antibody testing. Living patients with newly identified HIV infection were interviewed, and DNA sequence analysis was performed to compare genetic relatedness of their HIV to that of the dentist. Death certificates were obtained for decreased patients, and the medical records of those with diagnoses suggestive of HIV disease or drug abuse and those dying under the age of 50 years were reviewed in detail. RESULTS: There were 1192 patients who had undergone 9267 procedures, of whom 124 were deceased. A review of the death certificates of the deceased patients identified five who had died with HIV infection, all of whom were either homosexuals or users of illicit intravenous drugs. We were able to locate 962 (92%) of the remaining 1048 patients, and 900 agreed to be tested. Infection with HIV was documented in five of the 900 patients, including four who had clear evidence of risk factors for acquiring HIV infection. One patient who had only a single evaluation by the dentist denied high-risk behavior. Comparative DNA sequence analysis demonstrated that the viruses from the dentist and these five patients were not closely related. CONCLUSION: This study indicates that the risk for transmission of HIV from a general dentist to his patients is minimal in a setting in which universal precautions are strictly observed. Programs to ensure compliance with universal precautions would appear preferable to programs for widespread testing of dentists.

Discontinuing rheumatic fever prophylaxis in selected adolescents and young adults. A prospective study.

OBJECTIVE: To assess the safety of discontinuing prophylaxis with antimicrobial agents in patients judged to be at relatively low risk for recurrence of acute rheumatic fever. DESIGN: Observational cohort study. SETTING: Public health clinics in the Southeast Health District of Santiago, Chile. PATIENTS: Fifty-nine patients (19 men, 40 women) ranging in age at study entry from 15 to 44 years (mean, 24.5 years). Forty-eight had completed their prescribed period of prophylaxis. Eleven refused or were allergic to intramuscular benzathine penicillin G and were non-compliant with oral sulfadiazine. INTERVENTION: In patients who did not have carditis during their previous attack(s), prophylaxis was discontinued after 5 years or at age 18, whichever was longer. In those with only mild mitral regurgitation or healed carditis, prophylaxis was stopped after 10 years or at age 25. Symptomatic intercurrent streptococcal throat infections were treated with antibiotics. MEASUREMENTS: Patients were seen every 3 months during the study (July 1982 to September 1988). For the first 4.25 years, throat cultures as well as sera samples for antistreptolysin O and anti-DNAse B assays were obtained at each visit. RESULTS: During laboratory surveillance, significant increases in antibody titers were detected in 56 instances (28.1 [95% CI, 21.7 to 36.5] per 100 patient-years), and 29 isolations of group A streptococci occurred (14.5 [CI, 10.1 to 20.8] per 100 patient-years). The patients were followed for a total of 3349 patient-months, during which time two acute rheumatic fever recurrences were observed (0.7 [CI, 0.2 to 2.6] per 100 patient-years). No recurrences occurred during an outbreak of acute rheumatic fever in 52 patients in the study area in 1986. CONCLUSIONS: These and other data indicate that acute rheumatic fever prophylaxis can safely be discontinued in young adults judged to be at low risk for recurrence and who are maintained under careful prospective surveillance.