Clinical presentation of infective endocarditis caused by different groups of non-beta haemolytic streptococci.

Streptococci are common causes of infective endocarditis (IE) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has provided a practical tool for their species determination. We aimed to investigate if particular groups of non-beta heamolytic streptococci were associated with IE or to specific presentations thereof. The Swedish Registry of Infective Endocarditis was used to identify cases of IE caused by streptococci and a local database to identify cases of streptococcal bacteremia. The bacteria were grouped using MALDI-TOF MS and the clinical characteristics of IE caused by different groups were compared. We identified a group of 201 streptococcal IE isolates: 18 isolates belonged to the anginosus, 19 to the bovis, 140 to the mitis, 17 to the mutans, and seven to the salivarius groups. The mitis and mutans groups were significantly more common and the anginosus group less common among IE cases as compared to all cause bacteremia. Patients infected with the bovis group isolates were older, had more cardiac devices, and had more commonly prosthetic valve IE compared to IE caused by streptococci of the other groups. Twenty-one percent of patients needed surgery, and in-hospital mortality was 8% with no significant differences between the groups. Grouping of non-beta haemolytic streptococci using MALDI-TOF MS can provide a basis for decision-making in streptococcal bacteremia. IE caused by bovis group isolates have clinical characteristics distinguishing them from IE caused by other groups of Streptococcus.

Enterococcal endocarditis in the beginning of the 21st century: analysis from the International Collaboration on Endocarditis-Prospective Cohort Study.

Enterococci are reportedly the third most common group of endocarditis-causing pathogens but data on enterococcal infective endocarditis (IE) are limited. The aim of this study was to analyse the characteristics and prognostic factors of enterococcal IE within the International Collaboration on Endocarditis. In this multicentre, prospective observational cohort study of 4974 adults with definite IE recorded from June 2000 to September 2006, 500 patients had enterococcal IE. Their characteristics were described and compared with those of oral and group D streptococcal IE. Prognostic factors for enterococcal IE were analysed using multivariable Cox regression models. The patients' mean age was 65 years and 361/500 were male. Twenty-three per cent (117/500) of cases were healthcare related. Enterococcal IE were more frequent than oral and group D streptococcal IE in North America. The 1-year mortality rate was 28.9% (144/500). E. faecalis accounted for 90% (453/500) of enterococcal IE. Resistance to vancomycin was observed in 12 strains, eight of which were observed in North America, where they accounted for 10% (8/79) of enterococcal strains, and was more frequent in E. faecium than in E. faecalis (3/16 vs. 7/364 , p 0.01). Variables significantly associated with 1-year mortality were heart failure (HR 2.4, 95% CI 1.7--3.5, p <0.0001), stroke (HR 1.9, 95% CI 1.3--2.8, p 0.001) and age (HR 1.02 per 1-year increment, 95% CI 1.01--1.04, p 0.002). Surgery was not associated with better outcome. Enterococci are an important cause of IE, with a high mortality rate. Healthcare association and vancomycin resistance are common in particular in North America.

Warfarin therapy and incidence of cerebrovascular complications in left-sided native valve endocarditis.

Anticoagulant therapy has been anticipated to increase the risk of cerebrovascular complications (CVC) in native valve endocarditis (NVE). This study investigates the relationship between ongoing oral anticoagulant therapy and the incidence of symptomatic CVC in left-sided NVE. In a prospective cohort study, the CVC incidence was compared between NVE patients with and without ongoing warfarin. Among 587 NVE episodes, 48 (8%) occurred in patients on warfarin. A symptomatic CVC was seen in 144 (25%) patients, with only three on warfarin. CVC were significantly less frequent in patients on warfarin (6% vs. 26%, odds ratio [OR] 0.20, 95% confidence interval [CI] 0.06-0.6, p = 0.006). No increase in haemorrhagic lesions was detected in patients on warfarin. Staphylococcus aureus aetiology (adjusted OR [aOR] 6.3, 95% CI 3.8-10.4) and vegetation length (aOR 1.04, 96% CI 1.01-1.07) were risk factors for CVC, while warfarin on admission (aOR 0.26, 95% CI 0.07-0.94), history of congestive heart failure (adjusted OR 0.22, 95% CI 0.1-0.52) and previous endocarditis (aOR 0.1, 95% CI 0.01-0.79) correlated with lower CVC frequency.

Prosthetic valve endocarditis due to coagulase-negative staphylococci: findings from the International Collaboration on Endocarditis Merged Database.

Infective endocarditis due to coagulase-negative staphylococci is increasingly recognized as a difficult-to-treat disease associated with poor outcome. The aim of this report is to describe the characteristics and outcome of patients with prosthetic valve endocarditis (PVE) due to coagulase-negative staphylococci versus those of patients with PVE due to Staphylococcus aureus and viridans streptococci. Patients were identified through the International Collaboration on Endocarditis Merged Database. A total of 54 cases of coagulase-negative staphylococci PVE, 58 cases of S. aureus PVE, and 63 cases of viridans-streptococci-related PVE were available for analysis. There was no difference between the three groups with respect to the type of valve involved or the rate of embolization. However, heart failure was encountered more frequently with coagulase-negative staphylococci (54%) than with either S. aureus (33%; p=0.03) or viridans streptococci (32%; p=0.02). In addition, valvular abscesses complicated 39% of infections due to coagulase-negative staphylococci compared with 22% of those due to S. aureus (p=0.06) and 6% of those due to viridans streptococci (p<0.001). Mortality was highest in patients with S. aureus and coagulase-negative staphylococcal endocarditis (47 and 36%, respectively; p=0.22) and was considerably lower in patients with viridans streptococcal endocarditis (p=0.002 compared to patients with coagulase-negative staphylococcal endocarditis). The results of this analysis demonstrate the aggressive nature of coagulase-negative staphylococcal PVE and the substantially greater morbidity and mortality associated with this infection compared to PVE caused by other pathogens.

Enterococcal prosthetic valve infective endocarditis: report of 45 episodes from the International Collaboration on Endocarditis-merged database.

Enterococcal prosthetic valve infective endocarditis (PVE) is an incompletely understood disease. In the present study, patients with enterococcal PVE were compared to patients with enterococcal native valve endocarditis (NVE) and other types of PVE to determine differences in basic clinical characteristics and outcomes using a large multicenter, international database of patients with definite endocarditis. Forty-five of 159 (29%) cases of definite enterococcal endocarditis were PVE. Patients with enterococcal PVE were demographically similar to patients with enterococcal NVE but had more intracardiac abscesses (20% vs. 6%; p=0.009), fewer valve vegetations (51% vs. 79%; p<0.001), and fewer cases of new valvular regurgitation (12% vs. 45%; p=0.01). Patients with either enterococcal PVE or NVE were elderly (median age, 73 vs. 69; p=0.06). Rates of in-hospital mortality, surgical intervention, heart failure, peripheral embolization, and stroke were similar in both groups. Patients with enterococcal PVE were also demographically similar to patients with other types of PVE, but mortality may be lower (14% vs. 26%; p=0.08). Notably, 93% of patients with enterococcal PVE came from European centers, as compared with only 79% of patients with enterococcal NVE (p=0.03). Thus, patients with enterococcal PVE have higher rates of myocardial abscess formation and lower rates of new regurgitation compared to patients with enterococcal NVE, but there are no differences between the groups with regard to surgical or mortality rates. In contrast, though patients with enterococcal PVE and patients with other types of PVE share similar characteristics, mortality is higher in the latter group. Importantly, the prevalence of enterococcal PVE was higher in the European centers in this study.

Enterococcal endocarditis: 107 cases from the international collaboration on endocarditis merged database.

PURPOSE: To describe clinical features and outcomes of enterococcal left-sided native valve endocarditis and to compare it to endocarditis caused by other pathogens. SUBJECTS AND METHODS: Patients in the International Collaboration on Endocarditis-Merged Database were included if they had left-sided native valve endocarditis. Demographic characteristics, clinical features, and outcomes were analyzed. Multivariable analysis evaluated enterococcus as a predictor of mortality. RESULTS: Of 1285 patients with left-sided native valve endocarditis, 107 had enterococcal endocarditis. Enterococcal endocarditis was most frequently seen in elderly men, frequently involved the aortic valve, tended to produce heart failure rather than embolic events, and had relatively low short-term mortality. Compared to patients with non-enterococcal endocarditis, patients with enterococcal endocarditis had similar rates of nosocomial acquisition, heart failure, embolization, surgery, and mortality. Compared to patients with streptococcal endocarditis, patients with enterococcal endocarditis were more likely to be nosocomially acquired (9 of 59 [15%] vs 2 of 400 [1%]; P <.0001) and have heart failure (49 of 107 [46%] vs 234 of 666 [35%]; P = 0.03). Compared to patients with S. aureus endocarditis, patients with enterococcal endocarditis were less likely to embolize (28 of 107 [26%] vs 155 of 314 [49%]; P <.0001) and less likely to die (12 of 107 [11%] vs 83 of 313 [27%]; P = 0.001). Multivariable analysis of all patients with left-sided native valve endocarditis showed that enterococcal endocarditis was associated with lower mortality (odds ratio [OR] 0.49; 95% confidence interval [CI] 0.24 to 0.97). CONCLUSIONS: Enterococcal native valve endocarditis has a distinctive clinical picture with a good prognosis.

Emergence of endocarditis due to group D streptococci: findings derived from the merged database of the International Collaboration on Endocarditis.

The aim of the present study was to compare the epidemiological and clinical characteristics of Streptococcus bovis endocarditis with those of endocarditis caused by oral streptococci, using data obtained from a large international database of uniformly defined cases of infective endocarditis. S. bovis, a well-known cause of infective endocarditis, remains the common name used to designate group D nonenterococcal streptococci. In some countries, the frequency of S. bovis endocarditis has increased significantly in recent years. Data from the International Collaboration on Endocarditis merged database was used to identify the main characteristics of S. bovis endocarditis and compared them with those of infective endocarditis (IE) due to oral streptococci. The database contained 136 cases of S. bovis IE and 511 cases of IE due to oral streptococci. Patients with S. bovis IE were significantly older those with IE due to oral streptococci (63+/-16 vs. 55+/-18 years, P<0.00001). The proportion of streptococcal IE due to S. bovis increased from 10.9% before 1989 to 23.3% after 1989 (P=0.0007) and was 56.7% in France as compared with 9.4% in the rest of Europe and 6.0% in the USA (P<0.00001). Patients with S. bovis IE had more comorbidity and never used intravenous drugs. Complication rates, rates of valve replacement, and mortality rates were similar in the two groups. In conclusion, this study confirmed that S. bovis IE has unique characteristics when compared to endocarditis due to oral streptococci and that it emerged in the 1990s, mainly in France, a finding that is yet unexplained.

Prognostic factors in 61 cases of Staphylococcus aureus prosthetic valve infective endocarditis from the International Collaboration on Endocarditis merged database.

Staphylococcus aureus prosthetic valve infective endocarditis (SA-PVIE) is associated with a high mortality rate, but prognostic factors have not been clearly elucidated. The International Collaboration on Endocarditis merged database (ICE-MD) contained 2212 cases of definite infective endocarditis (as defined using the Duke criteria), 61 of which were SA-PVIE. Overall mortality rate was 47.5%, stroke was associated with an increased risk of death, and early valve replacement was not associated with a significant survival benefit in the whole population; however, patients who developed cardiac complications and underwent early valve replacement had the lowest mortality rate (28.6%).

Infective endocarditis: a diagnostic and therapeutic challenge for the new millennium.

This review on infective endocarditis (IE) is based on clinical studies carried out in Göteborg since 1984, data obtained from a Swedish national registry of IE since 1995 and existing literature. IE is still a great challenge in medicine, although improved bacteriological and echocardiographical techniques have facilitated diagnosis. In Sweden the incidence of IE is about 6 per 100,000 inhabitants a year. During recent decades IE has changed character. Patients are older, fever is often the only major symptom and a new murmur is less frequent. Streptococci, including viridans species and staphylococci, are still the most common bacteria found. Antibiotic treatment for 4-6 weeks may reduce mortality of IE to 30-50%. For further reduction, heart surgery is necessary in 20-25% of patients in order to remove infected tissues and restore valve function. Rapid diagnosis, careful antibiotic treatment and optimal surgery may reduce mortality associated with treatment to 10%. Antibiotic treatment is still mainly empiric. Penicillin and aminoglycoside for 2 weeks only seem to be effective in uncomplicated IE caused by alpha-streptococci. Otherwise, 4 weeks of treatment is needed, but aminoglycoside treatment may be reduced to 1 week in general and 2 weeks for enterococcal infections.

Incidence of beta-lactam-induced delayed hypersensitivity and neutropenia during treatment of infective endocarditis.

BACKGROUND: Long-term parenteral beta-lactam treatment is often complicated by adverse reactions that necessitate drug withdrawal. OBJECTIVE: To evaluate the incidence and mechanism of beta-lactam adverse reactions during an 8-year period in all episodes of suspected infective endocarditis in patients treated at a university-affiliated institution. METHODS: Patients with 215 consecutive episodes of beta-lactam treatment for 10 days or more were prospectively enrolled during 2 periods, January 1984 through December 1988 and January 1993 through December 1995, and compared with 51 episodes of vancomycin hydrochloride treatment for 10 days or more. Incidents of adverse reactions, such as fever, rash, or neutropenia, were registered. Neutrophil counts, eosinophil counts, and penicillin antibodies were studied. Patients with delayed adverse reactions to penicillin G sodium were rechallenged with penicillin v potassium. RESULTS: Incidence of delayed adverse reactions during treatment was 33% with beta-lactams compared with 4% with vancomycin. Rates of adverse event for beta-lactams increased continuously from treatment day 15 to day 30. A 6-fold difference in capacity to induce adverse events was found with different beta-lactams. Penicillin G induced neutropenia in 14% and any adverse event in 51% of treated episodes. Mean daily doses significantly influenced the frequency of adverse events. Occurrence of hemagglutinating penicillin antibodies was significantly related to patients whose penicillin-treated episodes were complicated with adverse events. Patients with delayed adverse reactions to penicillin G were safely rechallenged with penicillin. CONCLUSIONS: Incidence of delayed adverse reactions to beta-lactams increases sharply when parenteral treatment is extended beyond 2 weeks. Penicillin G is the most frequent inducer of adverse reactions among beta-lactams studied. An immunological reaction mediated by antibodies to the penicilloyl determinant may be involved in the pathogenesis, possibly enhanced by a dose-related toxic trigger mechanism. Beta-Lactam-induced neutropenia followed a uniform pattern, occurring after, on average, 21 days of treatment, and might be due to both immunologic and toxic effects of treatment. Patients with a late adverse reaction to penicillin can safely be re-treated with penicillin, although they should remain under close surveillance if treatment extends beyond 2 weeks.

Virulence factors of Staphylococcus aureus strains causing infective endocarditis--a comparison with strains from skin infections.

The objective was to study potential bacterial virulence factors in S. aureus endocarditis. S. aureus strains isolated from patients with well-classified episodes of infective endocarditis (IE) (n=26) were compared with control S. aureus strains from consecutive patients with skin infections (n=30). The potential virulence factors studied were Staphylococcal enterotoxin A-D (SEA, SEB, SEC, SED) and toxic shock syndrome toxin-1 (TSST-1) production and binding capacity to the extracellular matrix proteins: fibronectin, collagen type I, collagen type II and bone sialoprotein (BSP). None of the potential virulence factors studied was more prevalent among the IE strains. BSP binding was more often found in the control group with skin infections. Endocarditis patients with previous damage of the heart valves were more often infected by strains not producing any enterotoxin. No correlation was found between the potential bacterial virulence factors studied and IE. Concerning the toxins known to act as superantigens (SEA-E and TSST-1), the tendencies in this and other studies indicate that a larger study group might identify them as pathogenic factors in a subgroup of staphylococcal endocarditis.

Paracetamol-induced cholestatic and granulomatous liver injuries.

OBJECTIVE: To describe uncommon (previously unreported) types of adverse liver reactions to paracetamol. DESIGN: In addition to describing patients, with uncommon types of liver reactions to paracetamol, admitted to our hospitals, we surveyed all the liver reactions to paracetamol reported to the Swedish Adverse Drug Reactions Advisory Committee from 1973 to 1993. SETTING: The Swedish population of 8 million inhabitants. MEASUREMENT: Extensive medical evaluation. RESULTS: We found one case with a cholestatic liver reaction and one with granulomatous hepatitis. The reactions were probably idiosyncratic and took several months to disappear. CONCLUSION: In addition to the well-known dose-related toxic liver damage paracetamol may rarely cause non-dose-related severe, prolonged cholestasis or granulomatous hepatitis with cirrhosis.

Fever, C-reactive protein, and other acute-phase reactants during treatment of infective endocarditis.

BACKGROUND: Fever and sustained elevations of levels of C-reactive protein, erythrocyte sedimentation rate, and other inflammatory markers are common problems during treatment of infective endocarditis. We studied the value of these measurements during an 8-year period in all episodes of infective endocarditis treated in 1 university-affiliated institution. METHODS: A total of 193 consecutive episodes that fulfilled the criteria for infective endocarditis were prospectively enrolled during 2 periods, 1984 through 1988 and 1993 through 1995. Fever and results of serial measurements of C-reactive protein, erythrocyte sedimentation rate, white blood cell counts, and platelet counts were related to the clinical course of infective endocarditis. RESULTS: Fever persisted or recurred in 108 episodes (57%) despite appropriate antibiotic treatment. The causes of persistent fever and recurrent fever were different. Persistent fever that lasted 7 days or longer was caused by a complicating cardiac infection in 56% of these episodes. Recurrent fever, noted in 31% of all episodes and the major cause of fever during the third and fourth treatment weeks, was caused most often by hypersensitivity reactions to beta-lactams. Elevations in C-reactive protein levels were significantly prolonged in the episodes with complicated courses compared with the episodes with uncomplicated courses, while mean erythrocyte sedimentation rate remained unchanged during treatment, not differentiating between complicated and uncomplicated episodes. CONCLUSIONS: Fever during treatment must be analyzed in terms of persistence and recurrence to provide a basis for clinical decisions. Serial measurements of C-reactive protein are useful to monitor the response to antimicrobial therapy and to detect complications, while serial determinations of erythrocyte sedimentation rate are of no value.

C-reactive protein is more sensitive than erythrocyte sedimentation rate for diagnosis of infective endocarditis.

The objective of this study was to evaluate the sensitivity of C-reactive protein (CRP) elevation compared to erythrocyte sedimentation rate (ESR), leucocyte count and thrombocyte count in the diagnosis of infective endocarditis (IE). It was designed as a prospective study of suspected episodes of IE in adults in tertiary care at a university-affiliated department of infectious diseases. In 89 episodes of IE, CRP was available from the start of treatment. Median age was 66 years, 45 were men and 44 women. Median CRP concentration was found to be 90 (range 0-357) mg/l with only 4% normal values. Episodes involving native valves had higher CRP than episodes occurring with prosthetic valves. Staphylococcal origin, short duration of symptoms, short duration of fever and highest recorded temperature all correlated to higher CRP levels. The CRP response was also prominent among patients > 70 years old. Among non-responders, a few cases with simultaneous cirrhosis were noted. ESR was less sensitive than CRP, with a normal level in 28% of the episodes. It was concluded that CRP determination is superior to erythrocyte sedimentation rate, leucocyte count and thrombocyte count in the diagnosis of infective endocarditis.

Early surgery in infective endocarditis.

Optimal timing of surgical intervention in infective endocarditis is important in reducing mortality. We prospectively studied 126 consecutive episodes of infective endocarditis treated in one institution over 5 years, with special emphasis on long-term results and on the effects on outcome of surgical interventions. Twenty-six patients (21%) underwent acute surgery on median treatment day 14. Mortality during treatment was 8% for patients undergoing acute surgery vs. 11% for those not undergoing surgery, and the adjusted 5-year survival rate of acute surgically treated patients was 91%, compared with 69% for the medically treated patients. Using univariate analysis, excess mortality during 5 years follow-up was associated with new cardiac decompensation at entry (p < 0.01), age (p < 0.01), no acute surgery (p < 0.05) and mitral valve involvement (p < 0.05). Multivariate analysis showed new cardiac decompensation at entry to be an independent predictor of cardiac death at 5 years follow-up (relative risk 2.39; CI 1.05-5.45), while no surgery during active disease implied a relative risk of 3.45, though not statistically significant. Patients undergoing surgery very early (< or = 10 days of treatment) did not have a poorer outcome. Acute valve replacement, as compared with medical therapy only, might be important to increase both short-term and long-term survival in infective endocarditis.

Comparison of the von Reyn and Duke criteria for the diagnosis of infective endocarditis: a critical analysis of 161 episodes.

The newly proposed diagnostic criteria for infective endocarditis (Duke criteria) were evaluated in 161 consecutive episodes treated for suspected infective endocarditis (IE) at one institution over a 5-year period. A significantly higher proportion of episodes were diagnosed as definite endocarditis by the new Duke criteria compared with a diagnosis as definite or probable endocarditis by the older von Reyn criteria (68% vs 56%; p < 0.05). If all 161 episodes were to be reclassified, excluding pathological data, which are seldom available at the start of treatment, the Duke criteria classified significantly more episodes as 'definite' compared with the analogous category 'probable' endocarditis by the von Reyn criteria (60% vs 44%; p < 0.01). Forty-four pathologically proven episodes were reclassified in the same way, and 73% of these episodes were classified as 'definite' IE by the Duke criteria compared to 55% classified as 'probable' IE using the von Reyn criteria In 33 (20%) episodes no heart murmur could be detected on admission and the Duke criteria provided an initial diagnosis of 'definite' IE in 58% of these episodes compared with only 6% classified as 'definite' or 'probable' IE by the von Reyn criteria (p < 0.0001). The newly proposed Duke criteria are an improvement on the older von Reyn criteria in the clinical diagnosis of IE, especially in initial phase of treatment. However, the sensitivity when establishing a correct clinical diagnosis of 'definite' IE for the pathologically proven cases was only 73%. The category of 'possible' IE by the Duke criteria is confusing, since it does not say anything of the likelihood on an actual IE; the only objective fact is that no alternative diagnosis has been proven.

Epidemiologic aspects of infective endocarditis in an urban population. A 5-year prospective study.

A prospective study of the epidemiology of infective endocarditis (IE) in a well-defined urban population of 428,000 inhabitants during a 5-year period was carried out. All patients were treated in the same institution, and history, diagnostic procedures, and treatment were standardized. Of 233 consecutive suspected episodes of IE, 127 fulfilled the modified von Reyn criteria. After patients not living in the defined area were excluded, 99 episodes in 90 patients were analyzed in the epidemiologic part of the study. Of these, 33 episodes were definite endocarditis, verified by surgery or autopsy; 35 probable; and 31 possible endocarditis episodes. Another 34 episodes were found retrospectively and are included in the incidence calculation. The crude incidence was calculated to be 6.2/100,000 inhabitants per year, which is high compared to earlier studies. Adjusted to the population of Sweden, the incidence was 5.9/100,000 inhabitants per year. The annual incidence was higher for women, 6.6/100,000, than for men, 5.8/100,000. In the oldest age-group (80-89 years) the annual incidence was 22/100,000 in the prospective study and 30/100,000 if retrospective cases were included. Contrary to almost all other studies, we did not find a male predominance among our cases. Only 7% of patients were intravenous drug abusers, and 15% had a prosthetic valve. The most common bacteria were methicillin-susceptible Staphylococcus aureus (31%) and alpha-streptococci (28%); 12% of episodes were culture negative. The mortality from IE in the population was 1.4/100,000 inhabitants per year. A higher-than-expected incidence of IE was found, especially among older patients and women.

An outbreak of trichinosis in Lebanon.

In 1982 an outbreak of trichinosis occurred in an area of south Lebanon consisting of 4 villages, including 6440 persons. In 267 households, involving 2456 persons, typical clinical signs of Trichinella spiralis infection could be recognized among household members. Twenty-one of these households, including 193 persons, were randomly chosen for further studies. Nearly half of the household members (46%) had clinical symptoms consistent with acute trichinosis. 12 of 16 tested persons had high anti-Trichinella antibody titres (12 positive by indirect immunofluorescence (IIF) and 11 by enzyme-linked immunosorbent assay). Class-specific antibodies, IIF-immunoglobulin (Ig) G, IgM and IgA, were detected in most tested cases. Of the remaining 4 seronegative cases, 3 had a duration of clinical symptoms < or = 12 d. High peripheral eosinophilic counts (> 20%) were noted in 8 of 16 cases. In total, 15 of 16 cases were positive by one or more of these tests. The outbreak constituted one of the most extensive single outbreaks reported with a calculated > 1000 clinical cases. The cause was attributed to consumption of raw pork meat, an ingredient of kebbeh nayyeh, a favourite Lebanese dish.

A prospective study of neutropenia induced by high doses of beta-lactam antibiotics.

A prospective study on the effect of beta-lactam antibiotics on granulopoiesis was carried out in 29 consecutive patients with bacterial endocarditis. Fourteen patients received a high dose of benzylpenicillin, up to 18 g/day, but in only three of them could the treatment be fulfilled as planned, for a mean time of 25 days. In 11 benzylpenicillin treated patients treatment had to be discontinued because of fever, rash or neutropenia. Neutropenia appeared in seven patients after 14-24 (mean 22) days. No superinfection occurred during the neutropenic phase which lasted 2-12 days. Patients with neutropenia differed significantly from others in having a lowered pretreatment neutrophil count (3.2 vs 10.4). In 15 patients treated with other beta-lactams, three cases of fever and rash and one case of neutropenia were seen in patients treated with cloxacillin 12 g daily. It was concluded that a daily dose of 18 g of benzylpenicillin is too high for longer treatment periods and that patients with initial low counts of neutrophils have an increased risk of developing neutropenia.