Streptococcal Endocarditis Research Articles

Treatment of streptococcal and staphylococcal endocarditis.

Treatment of streptococcal and staphylococcal endocarditis.

Group B Streptococcal Infective Endocarditis

To the Editor. —We read with interest the report by Backes et al in the AprilArchives 1 concerning group B streptococcal (GBS) infective endocarditis. Recently, we have had the opportunity to attend two patients with GBS infective endocarditis who developed complications and died. Report of Cases. —Both were women, aged 71 and 63 years. They had not undergone manipulations prior to admission. The diagnosis was made on the basis of three blood cultures that yielded two strains of group B β-hemolytic streptococci ( Streptococcus agalactiae ), fever, petechiae, heart murmurs, splenomegaly, and echocardiographic findings compatible with valvular vegetations affecting the mitral valve in both cases. Both strains had a minimal inhibitory concentration of 0.06 mg/L of penicillin G sodium and the peak serum acid level was 1:1,028 in both cases. On admission, treatment was started with 24 million units of penicillin G sodium and 240 mg of gentamicin sulfate (daily) for

Role of culture conditions and immunization in experimental nutritionally variant streptococcal endocarditis.

The nutritionally variant streptococci (NVS) are usually isolated from patients with NVS endocarditis and recently have been serotyped into three groups. In the past, studies on microbial endocarditis have not analyzed the effect of the growth medium or growth phase on the bacteria used to induce the disease in the experimental rabbit model. Therefore, in this study various bacterial growth parameters were examined, including growth in semisynthetic or complex medium to the exponential or stationary phase of growth. The 50% infective dose ranged from 3.7 X 10(5) to 8.5 X 10(6) CFU for representative strains from each of the three serotypes grown under these conditions, indicating that there was no significant difference. The role of immunization was also examined in this model using organisms grown to the exponential phase in semisynthetic medium. Rabbits were immunized with heat-killed whole cells, high titres of specific antibody were produced as demonstrated by enzyme-linked immunosorbent assay, and then the rabbits were challenged with 20- to 100-fold 50% infective dose of the homologous strain. A total of 90 to 100% of the rabbits were protected from the disease process, as shown by the absence of the organisms from the heart valve 3 days after the challenge. Rabbits immunized with the amphiphile that replaces lipoteichoic acid in these organisms were not protected from challenge, demonstrating that another surface component is responsible for adherence or colonization or both. Finally NVS were incubated with radioiodinated fibronectin, fibrinogen, or laminin to determine whether these molecules aided in the adherence of the organisms to the heart valve. Only minor amounts of these components were bound to NVS as compared with controls. Therefore, NVS bind directly to the damaged heart valve or through an unknown mechanism.

PENICILLIN PROPHYLAXIS (PP) FOR EXPERIMENTAL STREPTOCOCCAL ENDOCARDITIS IS EARLY PENICILLIN TREATMENT

The aim of PP for endocarditis due to viridans streptococci (VS) is to prevent the onset of bacteremia. However, the incidence of postextraction bacteremia in children with cardiac disease after dental extraction under PP has been shown to be 21% (Hess et al, Ped 71: 554-558, 1983). Since the adherence of VS onto vegetations is recognized as an initial step in the pathogenesis of endocarditis, we studied the effect of P on adherence of VS in experimental endocarditis. 107-CFU penicillin-sensitive VS (MIC .01μg/ml, MBC .02μg/ml) were injected iv 30 min after im injection of procaine penicillin G (PPG) 250 mg/kg into Chinchilla rabbits with a left heart catheter in situ for 24 hrs. The rabbits were sacrificed 5 min, 0.5 hr, 2 hr, 4 hr and 48 hr after the injection of the VS, and the cardiac vegetations, induced by the catheter, were excized and cultured to determine whether or not colonization of the vegetations had been prevented by P. Results were: We conclude that PP does not prevent the colonization of cardiac vegetations by reducing the bacterial adherence, but sterilizes initially infected vegetations. Therefore, PP for experimental streptococcal endocarditis is in fact early treatment.

Treatment of streptococcal infective endocarditis

Patients with infective endocarditis caused by penicillin-sensitive streptococci (minimal inhibitory concentration for penicillin of 0.1 μg/ml or less) may be treated successfully with one of the following regimens: aqueous penicillin G administered intravenously for four weeks, intravenous aqueous penicillin G for four weeks combined with streptomycin for the first two weeks of therapy, or parenterally administered penicillin plus streptomycin for two weeks. A cure rate of at least 98 percent may be anticipated with each of these regimens. During a 12-year period among 142 patients treated for two weeks with penicillin and streptomycin, one (0.7 percent) had relapse and four (3 percent) had vestibular toxicity. The major advantage of the two-week regimen is that it is more cost-effective than the four-week regimens. The major disadvantage of the use of streptomycin is the relatively low risk of vestibular toxicity. Patients with enterococcal endocarditis were treated initially for four weeks with aqueous penicillin G together with either streptomycin (streptomycin-susceptible enterococci, 36 patients) or gentamicin (streptomycin-resistant enterococci, 20 patients). Compared with patients who had symptoms for less than three months, patients with symptoms for longer than three months had a higher relapse rate (0 percent versus 44 percent; p <0.001) and mortality (2.5 percent versus 25 percent; p <0.001). Patients with mitral valve endocarditis had a significantly higher relapse rate (25 percent) than patients with aortic valve infection (0 percent; p <0.01). Gentamicin-associated nephrotoxicity was more frequent (p <0.001) among patients treated with more than 3 mg/kg per day of gentamicin than among those treated with 3 mg/kg per day or less (100 percent versus 20 percent). Relapse and mortality rates did not differ significantly between patients treated with low-dose or high-dose gentamicin regimens. Patients who have had symptoms of enterococcal endocarditis for longer than three months or perhaps patients with mitral valve Infection should receive at least six weeks of penicillin therapy together with an aminoglycoside; patients without either high-risk factor may be treated successfully for four weeks.

Current issues in prevention of infective endocarditis

Prevention of infective endocarditis continues to concern health care providers in many specialties. The well-known lack of primary clinical trials in this area is not expected to change. Therefore, the evolution of recommendations and practice must be based on theoretic considerations and continuing assessment of secondary sources of information. Recent developments include a report of 52 cases In which antibiotic prophylaxis for Infective endocarditis was attempted but appeared to fail. Most of these patients had undergone dental procedures after oral penicillin prophylaxis, with subsequent development of streptococcal endocarditis. In two thirds, the organism was sensitive to the antibiotic used. Notably, the most common underlying cardiac lesion among these patients was mitral valve prolapse. However, two recent independent analyses have concluded that providing endocarditis prophylaxis for all patients with mitral valve prolapse during procedures that might cause bacteremia would not be cost-effective. This is primarily because mitral valve prolapse is common and endocarditis is relatively rare, resulting in an adverse risk-benefit ratio. Parenteral prophylaxis for mitral valve prolapse might even cause a net loss of life from anaphylaxis. On the other hand, for the individual patient or physician, the reassurance provided by attempted prophylaxis with oral penicillin can be purchased at low cost and low risk. Very few cases of infective endocarditis have been reported after gastrointestinal and other endoscopic procedures; most of these do not need antibiotic coverage. Prophylactic antibiotics should be restricted to those situations in which both the procedure and the underlying cardiac condition seem to pose significant risk, for example, endoscopic sclerotherapy of esophageal varices in patients with prosthetic heart valves. Newly revised recommendations have been issued by the Medical Letter, the American Heart Association, and the American Dental Association. These regimens are shorter and simpler than earlier versions.

Group B Streptococcal Infective Endocarditis

From 1970 to 1983, five patients with group B streptococcal endocarditis were treated at the Mayo Clinic, Rochester, Minn. The minimal inhibitory concentration and the minimal bactericidal concentration of penicillin were 0.09 microgram/mL or less and 1.56 micrograms/mL or less, respectively. The in vitro activity of cefazolin against group B streptococci was similar to that of penicillin. In three of the five cases, penicillin and streptomycin acted synergistically in vitro against group B streptococci. Four of the five patients were cured, three by use of an aminoglycoside combined with penicillin, ampicillin, or vancomycin. Three of the five patients had multiple large systemic emboli, and one of the three died of brain-stem infarct. Penicillin alone or in combination with an aminoglycoside is effective therapy for group B streptococcal endocarditis. Patients unable to tolerate penicillin may be treated with cefazolin or vancomycin. Clindamycin therapy should be avoided in patients with endocarditis caused by strains that are tolerant in vitro to clindamycin.

Group C Streptococcal Endocarditis

Although endocarditis is often caused by α-hemolytic streptococci, endocarditis due to β-hemolytic streptococci is rare. Most cases of β-streptococcal endocarditis are due to Lancefield groups B or G, whereas group C streptococci rarely cause endocarditis.1 Only 15 cases of endocarditis caused by group C streptococci, all in adults, have been reported.2-13 The rarity of this association is emphasized by the fact that Mohr et al13 reported one patient with group C streptococcal endocarditis from a series of 150,000 blood cultures. In addition, Cherubin and Neu14 found no cases of group C streptococcal endocarditis while reviewing 656 cases of infective endocarditis.

Successful prophylaxis of experimental streptococcal endocarditis with single doses of sublethal concentrations of penicillin.

Penicillin prophylaxis against experimental endocarditis due to a strain of Streptococcus intermedius isolated from a patient with endocarditis was studied in rats. The minimum bactericidal concentration of penicillin for this strain was more than 64 mg/l and was higher than the peak penicillin serum level obtained in rats 30 min after the iv injection of 60 mg/kg, and in man after an oral dose of 2 g of phenoxymethyl penicillin. Moreover timed kill curves performed in the presence of 64 mg/l of penicillin showed no decrease in the number of colony-forming units during the first 6 h of incubation and only a 95% decrease after 24 h. In addition, no bactericidal activity could be detected in the serum 30 min after penicillin injection, that is at the time of bacterial challenge. Using the minimum bacterial inoculum needed to produce endocarditis in 90% of control animals (ID90), penicillin successfully prevented endocarditis due to this strain. We conclude that penicillin may prevent streptococcal endocarditis by other mechanisms than bacterial killing.

Clinical evaluation of a fluorescent antibody test for the serological diagnosis of streptococcal endocarditis.

Serum fluorescent streptococcal antibody tests were carried out on 71 patients with clinically suspected infective endocarditis, and a final diagnosis of endocarditis was obtained in 46 patients. A serological diagnosis of streptococcal endocarditis was obtained in 10 patients who had persistently negative blood cultures, as fluorescent streptococcal antibody titres equal to or greater than 400 were detected against at least one of four strains of streptococci used as heterologous antigens. There were no false positive fluorescent antibody results with heterologous antigens during tests on 29 patients who had either non-streptococcal endocarditis, a final diagnosis other than endocarditis, or streptococcal sepsis not associated with endocarditis. A negative result with the heterologous antibody test could not, however, exclude a diagnosis of streptococcal endocarditis as six of 11 patients with endocarditis due to Streptococcus viridans or Str bovis confirmed on blood culture had serum fluorescent antibody titres less than 400 against all the heterologous streptococcal antigens tested. Homologous fluorescent streptococcal antibody titres equal to or greater than 400, using the patient's own blood culture isolate as the antigen, were found in the serum samples of 14 of 15 patients with endocarditis caused by viridans streptococci, three patients with enterococcal endocarditis, two patients with endocarditis caused by Str pneumoniae, and one patient with Str bovis endocarditis. In contrast, all five patients who had clinically insignificant streptococcal bacteraemias had serum fluorescent homologous antibody titres of only 100 or less. These results showed that the homologous serum fluorescent streptococcal antibody test could help to decide the clinical importance of a streptococcus which is initially isolated from only one or two of a number of inoculated blood culture bottles.

Late prosthetic valve endocarditis. Bacteriological findings and prognosis in 29 cases.

Of 296 incidences of infectious endocarditis seen between 1971 and 1980, 29 cases of late prosthetic valve endocarditis (10%) occurred in 26 patients who had undergone valve replacement more than two months previously. The prosthesis was mitral in 8 cases, aortic in 9 cases, and multiple in 12 cases. The clinical picture consistently associated fever together with a regurgitation murmur in 12 cases (41%), a splenomegaly in 7 cases, a neurologic accident in 13 cases and other signs of endocarditis in 10 cases. Blood cultures were positive in 28 cases. The diagnosis was confirmed anatomically in 11 cases. Thirty-one causative agents were identified: 15 streptococci (48%), most of them were group D (11/15), 11 staphylococci (35%) 6 Staphylococcus aureus, 5 Staphylococcus coagulase negative and 5 other species. Two relapses and 3 recurrent infections were noted. The death rate was 58% with some factors being associated with a higher death rate: non-streptococcal micro-organism (87%) regurgitation murmur (83%) cardiac failure with dysfunction of the prosthesis (89%) neurologic complication (91%). Eight valve replacements were performed within a mean period of 32 days after the onset of the antibiotherapy with a death rate of 75%. It decreased to 50% for patients treated with antibiotic alone, and as low as 23% for Streptococcal endocarditis. These results suggest that earlier and more frequent indications for cardiac valve replacement could be an alternative to improve the prognosis.

Factors Affecting Survival in Prosthetic Valve Endocarditis: Review of the Effectiveness of Prophylaxis

We review factors affecting survival of 44 episodes of prosthetic valve endocarditis occurring in 39 patients from 1965 to 1982. The mortality was 31.8 percent (14/44), and 21.6 percent (8/37) if the fungal cases are excluded. The development of a new murmur of valvular regurgitation in 18 patients led to valve replacement or death in every patient. Streptococcal endocarditis in 11 patients resulted in no deaths and only two valve replacements; staphylococcal infections had a mortality of 27.1 percent (6/22). Length of medical therapy before valve replacement did not relate to a successful outcome. Eight cases of early staphylococcal endocarditis occurred in which the organism was susceptible to the prophylactic antibiotic therapy. Changes in prophylaxis have led to no cases of early endocarditis over the past three years in 261 valve replacements.

Group C streptococcal endocarditis associated with intubation-induced tracheal stenosis

We describe a 44-year-old woman with Group C haemolytic streptococcal endocarditis who developed tracheal stenosis as a result of endotracheal intubation. She recovered fully following valve replacement for continuing left ventricular failure due to mitral and aortic incompetence and subsequent resection of the stenosed tracheal segment with reanastomosis of the trachea.

Successful prophylaxis against experimental streptococcal endocarditis with bacteriostatic antibiotics : Glauser MP, Francioli P. J Infect Dis 146:806, 1982

Successful prophylaxis against experimental streptococcal endocarditis with bacteriostatic antibiotics : Glauser MP, Francioli P. J Infect Dis 146:806, 1982

Serious infections due to group G streptoccocci: Report of 15 cases with in vitro-in vivo correlations

Serious infections due to group G streptococci have been infrequently reported. Fifteen such cases are described. Endovascular infection, particularly endocarditis, and septic arthritis were the most common clinical syndromes observed. Despite exquisite in vitro sensitivity of group G streptococci to penicillin G, the in vivo clinical response was disappointing in six of nine patients with either endocarditis or septic arthritis. The group G streptococcal isolates from the patients in this study were uniformly sensitive to the inhibitory and killing action of penicillin G, ampicillin, cefotaxime, cephalothin, cefoxitin, and vancomycin. In contrast, clindamycin, erythromycin, and chloramphenicol had relatively poor bactericidal activity against these strains, including several “tolerant” strains. Timed-kill studies with penicillin G revealed impaired killing of group G streptococci at in vitro conditions of high inocula and stationary growth phases. This may partially explain the poor clinical responses in cases of group G streptococcal endocarditis.

Humoral reactions in human endocarditis due to Streptococcus bovis: evidence for a common S bovis antigen.

Humoral reactions to native culture filtrates of Streptococcus bovis were studied in patients with endocarditis by means of two-dimensional crossed immunoelectrophoresis. Serum from patients with S bovis endocarditis produced eight different precipitin arcs. Lex antigen cross-reacted with sera from patients with viridans streptococcal endocarditis, and TA antigen cross-reacted with ribitol teichoic acid-positive sera from patients with Staphylococcus aureus bacteremia. One antigen, common (c), was immunoreactive with all 10 sera from S bovis-infected patients. Antibody to this antigen was not found in sera from 77 patients with gram-positive bacteremia or in 29 other control sera. Common (c) antigen was found in all strains of S bovis isolated from patients. Rabbits immunized with formalinized S bovis cells of human origin also produced antibody to common (c) antigen. Common (c) may be an important antigen of S bovis and may in fact define this organism serologically.

Activity of rifampin against viridans streptococci.

Optimal antimicrobial therapy for viridans streptococcal endocarditis remains controversial. Rifampin was bactericidal at less than 0.2 micrograms/ml for ten strains of viridans streptococci isolated from patients with endocarditis. Administration of rifampin to one endocarditis patient already receiving penicillin and gentamicin increased the serum bactericidal activity fourfold. Rifampin has been effective in combination therapy for serious staphylococcal and enterococcal infections. The combination of penicillin and rifampin may be an effective, less toxic alternative to penicillin and streptomycin for the treatment of viridans streptococcal endocarditis.

Studies of the Chemotherapy of Endocarditis: Correlation of in Vitro, Animal Model, and Clinical Studies

Bactericidal antibiotic activity is necessary for cure of bacterial endocarditis. The animal model of this disease has proved extremely useful for determining the in vivo significance of in vitro observations of antibiotic effect. A review and correlation of data from in vitro, animal model, and clinical studies regarding p-lactam therapy of streptococcal and staphylococcal endocarditis are presented. Although most in vitro findings have predicted therapeutic response to infection in experimental animals and humans, discrepancies, such as the tolerance phenomenon in Staphylococcus aureus and the efficacy of certain p-lactam-aminoglycoside combinations in enterococcal infections, do exist. In general, where examples exist, the results in animal models correlate with results from clinical studies of endocarditis. The goal of therapy for infectious diseases is to achieve maximal efficacy with a minimum of toxicity, time, and expense. The choice of an optimal antibiotic regimen is based on accumulated clinical experience and the results of in vitro testing. In most instances the determination of antibiotic susceptibility, usually by growth inhibition, has provided an acceptable guide in therapy. For infections in which host defenses are active, the use of drugs that arrest growth are usually effective, and such activity can be predicted by standard susceptibility testing. When host defenses are impaired, antibiotic regimens must kill the infecting organism. Thus, in vitro assays that measure bactericidal activity and accurately reflect in vivo action acquire greater significance. Bacterial endocarditis is an infection in which host defenses are clearly impaired and for which a bactericidal effect must be produced by the antibiotics in order to ensure cure. In this paper we will review the accumulated

Successful single-dose amoxicillin prophylaxis against experimental streptococcal endocarditis: evidence for two mechanisms of protection.

Amoxicillin prophylaxis against experimental endocarditis due to one nontolerant and two tolerant strains of streptococci was studied in rats. Single-dose amoxicillin protected against the two tolerant strains in animals challenged with the 90% infective dose (ID90), but protection diminished with increasing inoculum sizes. Protection against the nontolerant strain was successful with inocula that were 100- and 1,000-fold larger than the ID90. Close correlation existed between the speed of bacterial killing in vitro, the time of exposure to bactericidal levels in vivo, and the range of inocula against which prophylaxis was effective. Amoxicillin seemed to protect by at least two mechanisms. (1) When in vitro tests indicated adequate bacterial killing, protection was independent of the inoculum size and was probably conferred by bacterial killing. (2) When in vitro tests indicated bacterial inhibition but not killing, protection was inoculum-dependent and was probably mediated by inhibition of bacterial adherence.

Antibiotic treatment of infective endocarditis.

At least 85% of patients with infective endocarditis can be cured with effective therapy. Streptococci or staphylococci cause 75% of cases of endocarditis. Patients with penicillin-sensitive viridans or nonenterococcal group D streptococcal endocarditis may be treated successfully with aqueous penicillin G alone for four weeks or with combined penicillin and streptomycin for two weeks. Enterococcal endocarditis should be treated for four to six weeks with a combination of aqueous penicillin G together with either streptomycin or gentamicin. Patients with endocarditis caused by Staphylococcus aureus should receive antimicrobial therapy for four to six weeks with a semisynthetic penicillin (nafcillin or oxacillin) or a cephalosporin such as cephalothin or cefazolin. In urgent cases where empiric antimicrobial therapy is necessary before the causative organism is identified, a combination of aqueous penicillin G, nafcillin, and gentamicin is effective therapy.