Streptococcal Endocarditis Research Articles

Medical treatment or surgical intervention? A cooperative retrospective study on infective endocarditis. Timing of operation.

Two hundred and five patients treated for infective endocarditis over the last 10 years were reviewed. There were 185 cases of native valve endocarditis (NVE) and 20 of prosthetic valve endocarditis (PVE). In the NVE group there were 175 clinically active patients and 10 non-active patients. The mortalities among 108 non-surgical and 57 surgical patients were 15.7% and 14.0%, respectively. Leading causes of deaths in the former were cardiac failure, embolism and cerebral hemorrhage. Patients with embolism showed significantly higher mortality. Culture negative endocarditis resulted in almost the same incidence of hospital death and urgent operation as staphylococcal endocarditis, and a higher incidence than streptococcal endocarditis. In 9 of 33 patients operated at our hospital, surgery was performed on an urgent basis and one NYHA class IV patient died. Indications for operation were intractable cardiac failure, uncontrollable infection and angina. In the PVE group, 3 of 4 patients operated in the active stage died of severe cardiac failure generated preoperatively. The only survivor was a patient operated early under stable hemodynamics. These results suggest that culture negative endocarditis should be observed as closely as staphylococcal endocarditis and early operation should be considered for patients with progressive cardiac failure, embolism and uncontrollable infection.

Teicoplanin monotherapy of serious infections caused by Gram-positive bacteria: a re-evaluation of patients with endocarditis or Staphylococcus aureus bacteraemia from a European open trial

We have examined case records for patients who received teicoplanin alone for endocarditis or Staphylococcus aureus bacteraemia. All patients with streptococcal endocarditis were cured (viridans group 14/14; Group D 4/4). Cure rates for other organisms were: Enterococcus faecalis 3/5; S. aureus 5/10 and coagulase negative staphylococci 2/3. Doses for six patients who failed because of poor response were 3.3-4.2 mg/kg. Teicoplanin treatment cured 41/48 patients with S. aureus bacteraemia; treatment failed in two patients because of adverse events. Doses in the remaining treatment failures were 2.1-5.0 mg/kg. In comparison, 48 patients in Dundee hospitals received ten different drugs in 20 combinations for S. aureus bacteraemia; 29 patients received cloxacillin or flucloxacillin but initial doses varied from 0.25-2.0 g. We conclude that the European database does provide evidence that teicoplanin monotherapy is effective for serious infection with Gram-positive bacteria. Doses for staphylococcal infection should probably be at least 6 mg/kg. The upper limit of the teicoplanin dosage range remains to be determined but there is evidently considerable confusion about appropriate regimens for 'standard' therapy.

Native Valve Bacterial Endocarditis Due to Staphylococcus Epidermidis. A Community Acquired Infection Following an Acute Course.

Staphylococcus epidermidis (SE) is the leading pathogen of prosthetic valve endocarditis. At the same time it is a very rare cause of native valve endocarditis and it follows a clinical course and outcome similar to Streptococcal viridans endocarditis. We report here the case of a 41-year-old man with a community acquired SE endocarditis of a native aortic valve. Despite early surgical intervention, the case followed an acute and fatal course.

Streptococcal Endocarditis Temporally Related to Transesophageal Echocardiography

A case of streptococcal sanguis endocarditis temporally related to a transesophageal echocardiogram is reported; and the literature on the incidence of bacteremia occurring during transesophageal echocardiography is reviewed. On the basis of this case and review of the literature, a reevaluation of the current guidelines for endocarditis prophylaxis during this procedure is recommended.

Successful Prophylaxis of Experimental Streptococcal Endocarditis with Single-Dose Amoxicillin Administered after Bacterial Challenge

Rats with catheter-induced aortic vegetations were challenged intravenously with various inoculum sizes of tolerant Streptococcus sanguis or Streptococcus faecalis. Single-dose amoxicillin (40 mg/kg) was given intravenously either 30 min before or 30-240 min after bacterial challenge. Prophylaxis of endocarditis against both strains was successful when the inocula used for challenge were in the range of the minimum inoculum producing bacterial endocarditis in 90% of control animals (ID90) but was less effective or failed with larger inocula or when amoxicillin administration was delayed up to 240 min after bacterial challenge with S. sanguis. In a group of rats profoundly depleted of neutrophils by a rabbit anti-rat neutrophil serum given 30 min after challenge with S. faecalis at ID90, single-dose amoxicillin administered simultaneously with the antiserum was protective, indicating that neutrophils were not required for successful endocarditis prophylaxis.

Tolerance and efficacy of parenterally administered penicillin-streptomycin and orally administered amoxicillin or penicillin V for prophylaxis of experimentally induced streptococcal endocarditis

A regimen of a single intramuscular dose of penicillin G-streptomycin was compared with regimens of three oral doses of amoxicillin and two oral doses of penicillin V to prevent Streptococcus sanguis endocarditis in rabbits with experimentally induced valvular heart lesions. Challenge doses of 10(4), 10(6), and 10(8) CFU of a strain of S. sanguis highly tolerant to penicillin and amoxicillin were used. The combination of penicillin and streptomycin was the only regimen tested that provided full protection even against the highest inoculum concentration. A single oral dose of penicillin V (36 mg/kg) or amoxicillin (50 mg/kg), two oral doses of penicillin V (36 and 18 mg/kg with a 7-h interval between doses), or six oral doses of amoxicillin (50 mg/kg followed by 8.5 mg/kg at 8-h intervals) protected recipients of the lowest inoculum concentration; protection diminished with increasing inocula. In contrast, administration of two high oral doses of amoxicillin (50 mg/kg) with a 10-h interval between doses provided full protection against challenge doses of 10(4) and 10(6) CFU, preventing endocarditis in 10 (66%) of 15 recipients of 10(8) CFU. All regimens evaluated were highly effective in preventing endocarditis when rabbits were challenged with 10(4) CFU. The combination of penicillin and streptomycin was the best regimen tested. Administration of two high oral doses of amoxicillin (50 mg/kg) with a 10-h interval between doses led to significantly fewer infections when compared with the other oral regimens when rabbits were challenged with 10(6) and 10(8) CFU.

Does administration of an aminoglycoside in a single daily dose affect its efficacy and toxicity?

Treatment efficacy, oto- and nephrotoxicity, and aminoglycoside pharmacokinetics were evaluated in a prospective, comparative, randomized clinical study of aminoglycosides given once a day or three times a day for severe infections. Sixty patients were treated with netilmicin or gentamicin 4.5 mg/kg bodyweight/day, either once a day or divided into three doses a day. The patients were allocated randomly to the different groups. The clinical effect was difficult to compare in the different groups, because of the small numbers of patients. Therapeutic failures were seen in seven patients (three after one and four after three doses per day). Two patients, one with Staphylococcus aureus endocarditis and one with streptococcal endocarditis, on netilmicin once daily and conventional high-dose therapy with a penicillin had positive blood cultures after five and seven days of treatment, respectively. Vestibular function and hearing acuity were examined by serial audiograms and electronystagmograms. In spite of extensive diagnostic evaluation, only two cases of ototoxicity were detected. One patient treated with gentamicin three times a day developed vertigo and a severe abnormality of her electronystagmogram. One young patient treated with gentamicin once daily had a slight bilateral reduction of hearing. Nephrotoxicity was mild and did not differ in the four treatment groups. This was the first investigation of a once-daily dosing regimen conducted in seriously ill patients with systemic infections. We could not demonstrate any evidence that aminoglycoside treatment once daily has greater oto- or nephrotoxicity than the traditional three times daily regimen.

Neurological Presentations of Native Valve Endocarditis

In a prospective study of 178 episodes of community-acquired native valve infective endocarditis seen at St Thomas' Hospital between 1969 and 1987, 59 patients (33 per cent) presented with neurological disorders that included meningitis, toxic confusion, major thromboembolic phenomena and headache. A neurological presentation occurred in 54 per cent of all cases of staphylococcal endocarditis, but in only 19 per cent of episodes of 'viridans' streptococcal and enterococcal endocarditis. Overall one-third of patients with staphylococcal endocarditis presented with clinical features of meningitis (40 per cent with no cardiac murmur). The mortality rate for community-acquired native valve endocarditis was higher for those with a neurological presentation than without.

Infective Endocarditis in Children: The Changing Profile

This article discusses the principles for diagnosis and treatment of infective endocarditis in children. There has generally been a consistent volume of streptococcus endocarditis, the major lesion in pediatric endocarditis, but there has been an increase in Staphylococcus aureus endocarditis as well as neonatal endocarditis. Neonatal endocarditis is a severe form of the disease.

Antibiotics in Endocarditis due to Nutritionally Deficient Streptococci

To the Editor.— Recently, the American Heart Association's Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease 1 gave their recommendations for the treatment of streptococcal endocarditis, including that caused by nutritionally deficient variants. We feel their recommendation of 4 weeks of intravenous penicillin with at least 2 weeks of an aminoglycoside for treatment of endocarditis caused by nutritionally deficient variants deserves comment. Previous studies 2-4 have demonstrated the isolation of penicillin-resistant strains 5 and that minimal inhibitory concentrations to penicillin of 0.12 μg/mL or greater occur in up to one third of the strains tested. In clinical use, the therapy of penicillin and an aminoglycoside for nutritionally deficient streptococcal endocarditis has resulted in persistently positive blood cultures or positivevalue culture in 38% of the cases reviewed, 5 as compared with the 25% failure rate noted in enterococcal endocarditis. 1 Mortality in patients with nutritionally deficient streptococcal endocarditis who received penicillin

Evaluation of Antibiotic Diffusion into Cardiac Vegetations by Quantitative Autoradiography

The reason bacterial endocarditis is difficult to cure has been controversial for many years. One explanation could be that antibiotic diffusion inside the vegetations is heterogeneous. This hypothesis was investigated by means of an autoradiographic study of diffusion of labeled antibiotics into large infected cardiac vegetations of nutritionally variant Streptococcus endocarditis in rabbits. Ten days after infection, 653 microCi of [3H]penicillin, 410 microCi of [3H]tobramycin, or 174 microCi of [14C]teicoplanin were injected iv over 30 min. Thirty minutes after the end of infusion (T30), vegetation/blood radioactivity ratios were 2.48 +/- 1.27, 2.49 +/- 0.67, and 3.94 +/- 1.19 for penicillin, tobramycin, and teicoplanin, respectively. Autoradiography clearly showed that distribution of the three drugs was different: Tobramycin was homogeneously distributed; penicillin was more concentrated at the periphery but still reached the center of vegetations; teicoplanin was concentrated only at the periphery. The same distribution pattern was observed with teicoplanin at T120 (i.e., one t1/2 beta later) and also after simultaneous infusion of a therapeutic dose (15 mg/kg) of cold teicoplanin. The diffusion gradient exhibited by some antibiotics could explain the difficulty in sterilizing vegetations despite high local concentrations, and the deleterious effect of the size of the vegetations on the therapeutic response.

Pharmacokinetic Comparison of Two Models of Endocarditis Prophylaxis with Amoxycillin

From studies on prophylaxis against experimental streptococcal endocarditis using amoxycillin in a single dose, it has been deduced that serum concentrations above 0.12 mg/l should be maintained for at least 10 h after antibiotic administration. Since concentrations above this level are reported to occur following an oral dose of 3 g of amoxycillin, this doses for prophylaxis has become widely accepted in USA and the UK, and presently also in Sweden. Nevertheless, in individuals who cannot tolerate a high single dose of amoxycillin, there is need for an alternative dosage regimen. In the present study, we have compared the pharmacokinetics in 12 healthy volunteers, of a single dose of 3 g of amoxycillin with those of 1 g as single dose or combined with 1 g of probenecid. The combination resulted in an AUC twice as large as that achieved after 1 g of amoxycillin, and was slightly, but not significantly, larger than that after 3 g. However, amoxycillin concentrations above 0.12 mg/l were sustained for almost 14 h with the combination as compared to 10.4 hours following 3 g of amoxycillin only (p less than 0.001). Thus, the combination should be a convenient alternative in patients unable to tolerate a higher oral dose of amoxycillin, and in situations when an antibacterial effect of longer duration is desired.

3H-spiramycin penetration into fibrin vegetations in an experimental model of streptococcal endocarditis.

In-vivo diffusion of labelled spiramycin into fibrin was investigated in a rabbit model of left sided subacute endocarditis caused by a nutritionally variant streptococcus that produces large fibrin vegetations. Animals received one 30 min infusion of different doses of 3H spiramycin alone (73.4 +/- 3.5 microCi and 846 microCi) or 57.5 +/- 3.5 microCi in combination with 50 mg/kg 'cold' spiramycin. Thirty minutes after the end of infusion (T30) these vegetation/blood and vegetation/muscle ratios were between 1 and 2 and the vegetation/plasma ratio was between 2 and 4 for the three doses tested. Autoradiography showed that 3H spiramycin was homogeneously distributed throughout the vegetation in comparison with some other drugs. On the other hand, there were considerable differences in antibiotic concentration among different vegetations in a single animal.

Spontaneous splenic rupture as complication of infective endocarditis

A case is reported of spontaneously ruptured spleen occuring as a fatal complication of Group B streptococcal endocarditis, despite control of infection with antibiotics and early surgery.

Group A β-hemolytic streptococcal endocarditis precipitating rupture of sinus of Valsalva aneurysm: Evaluation by two-dimensional, Doppler, and contrast echocardiography

Group A β-hemolytic streptococcal endocarditis precipitating rupture of sinus of Valsalva aneurysm: Evaluation by two-dimensional, Doppler, and contrast echocardiography

Left ventricular pseudoaneurysm due to penetrating injury of the chest: An echocardiographic diagnosis

5. Ramirez CA, Naraqi S, McCulley DJ. Group A P-hemolytic streptococcus endocarditis. AM HEART J 1984;108:1383-6. Shaffer EM, Snider AR, Beckman RH, Behrendt DM, Peschiera AW. Sinus of Valsalva aneurysm complicating bacterial endocarditis in an infant: diagnosis with two-dimensional and Doppler echocardiography. J Am Co11 Cardiol 1987; 9:588-91. Vered Z, Roth S, Benjamin P, Motro M, Neufeld HN. Ruptured sinus of Valsalva: demonstration by contrast echocardiography during cardiac catheterization. AM HEART J 1985;109:365-6. Valdes-Cruz LM, Pierone DR, Roland JM, Varghese PJ. Echocardiographic detection of intracardiac right-to-left shunts following peripheral vein injections. Circulation 1976;54:558-62. Gillam LD, Kaul S, Fallon JT, et al. Functional and pathologic effects of multiple echocardiographic contrast injections on the myocardium, brain and kidney. J Am Co11 Cardiol 1985;6:687-94.

Group G streptococcal endocarditis: two case reports, a review of the literature and recommendations for treatment

Two cases of endocarditis caused by a group G streptococcus are reported and the literature on group G streptococcal endocarditis is reviewed. The onset of illness is usually acute and the portal of entry for the organism through the skin. The left side of the heart is mainly involved and in about 50% cases the endocarditis arises on a normal valve. Most patients develop complications, both embolic and cardiac, and the mortality is high (36%). We suggest that patients with proven group G streptococcal endocarditis should be treated with large doses of benzyl penicillin and with an aminoglycoside for not less than 4 weeks. Patients with complications should be referred to a cardiothoracic centre. We should be glad to know details of complications, treatment and outcome in other cases of group G streptococcal endocarditis.

Analysis of cross-protection between serotypes and passively transferred immune globulin in experimental nutritionally variant streptococcal endocarditis.

Nutritionally variant streptococci (NVS), which account for 5 to 10% of all cases of streptococcal endocarditis, were recently subdivided into three serotypes. In the past, using a rabbit endocarditis model, I demonstrated that by immunization of rabbits with NVS and by challenge with a strain from the homologous serotype a level of 90 to 100% protection was elicited. In the present study, the level of cross-protection between strains from different serotypes was measured. No cross-protection was demonstrated between serotype I and II or III strains. However, significant cross-protection was observed when serotype II and III strains were analyzed in the model. Since high levels of immunoglobulin G were demonstrated against the surface of the NVS after immunization, passive transfer experiments were initiated. Even at comparable levels of surface immunoglobulin G, none of the rabbits given immune globulin were protected against challenge with a dose of live NVS that equaled 20 times the 50% infective dose. Therefore, it appears that components from the immune system, in addition to humoral components, are required for active protection against NVS endocarditis.

Infective endocarditis 1973-1984 at the Bergen University Hospital: clinical feature, treatment and prognosis.

During the period 1973-1984, 72 patients with infective endocarditis (IE) were hospitalized in the medical department, Bergen University Hospital. The male/female ratio was 1.25/1, the mean age 55.3 years. 35 infections were caused by streptococci, 18 by staphylococci, 6 by other microorganisms and in 13 cases no causal organism was found. Only 13 patients had rheumatic heart disease. The overall mortality was 35%, and the mean age of the patients who died was 65 years. The case fatality rates for staphylococcal and streptococcal endocarditis were 61 and 24% respectively. In the period 1973-1978 the case fatality rate was 50% compared to 26% during 1979-1984. The proportion of patients with culture-negative endocarditis was reduced from 31 to 11% from the first to the second half of the study and the percentage of patients who received antibiotics before diagnosis decreased from 81 to 58%. Valve replacement was performed in 4 patients with staphylococcal and 15 with streptococcal infections. Seven cases (mean age 73.4 years) were diagnosed at necropsy; 3 with staphylococcal infections. With increased clinical awareness of IE, liberal use of blood cultures, better diagnostic tools and earlier surgical intervention, especially in staphylococcal infections, a further reduction in mortality should be possible.

Antibiotic therapy of nonenterococcal streptococcal and staphylococcal endocarditis: current regimens and some future considerations.

Regimens for endocarditis caused by these bacteria are generally based on high dosage of a beta-lactam antibiotic, penicillin in the case of streptococci and a penicillinase-resistant penicillin for Staphylococcus aureus, with vancomycin substituted for beta-lactam resistant staphylococci, including coagulase-negative staphylococci. The addition of other antimicrobial agents, such as aminoglycosides (or, in the case of staphylococci, sodium fusidate or rifampicin) may increase bactericidal efficiency, or allow shorter courses, but problems of toxicity or emergence of resistance may occur. Optimal regimens are discussed, and newer agents of possible usefulness are reviewed.