Gentamicin-resistant bacillary infection. Clinical features and amikacin therapy.

Infections caused by gentamicin sulfate-resistant Pseudomonas aeruginosa and Serratia marcescens have occurred in multiple areas of our hospitals and have caused serious clinical illness and death. Isolates of Pseudomonas organisms were sensitive to some alternative drugs including collstin sulfate, but isolates of Serratia organisms were often resistant to all commercially available parenteral antimicrobiais. All isolates were inhibited by amikacin sulfate, and 95% were killed by concentrations achievable in serum with recommended doses. Twenty patients with hospital-acquired infections, including ten with septicemia, were treated with amikacin. Eighteen of the 20 patients had a good clinical and bacteriologic response. Ototoxicity and nephrotoxicity each occurred in one patient.     

Gram-negative bacillary endocarditis. Interpretation of the serum bactericial test.

Although the serum bactericidal test is commonly used in the management of infective endocarditis, little has been written about its validity or limitations. We report three cases of gram-negative bacillary endocarditis (Pseudomonas aeruginosa, Vibrio fetus and Serratia marcescens) encountered in 1 year at a Veterans Administration hospital. Serum bactericidal titers were considered necessary to identify inadequate antibiotic regimens or to avoid unnecessary drug toxicity. The limitations of the test, particularly those pertaining to gram-negative infections, are reviewed. Misleading results during treatment with aminoglycoside antibiotics could be due to the tendency of serum to become alkaline on standing. A detailed study of the interaction of the complement-dependent bactericidal system of serum with eight antibiotics is presented. In the context of the serum bactericidal test, the interaction was additive or synergistic in 15 of 16 determinations, indicating the need to include a control study of serum sensitivity of the infecting microorganism in each case.     

Q fever endocarditis

Despite a worldwide distribution of Coxiella burnetii, only single cases of Q fever endocarditis have been reported outside Great Britain and Australia. We present 10 patients; five were female, only four had a history of environmental exposure, and the mitral valve was involved as commonly as the aortic valve. One patient had congenital aortic stenosis, and three patients had a prosthetic valve. We confirm the importance of hepatic involvement, thrombocytopenia and hypergammaglobulinemia as diagnostic features. Diagnosis was established by finding an elevated complement-fixing antibody to Phase I C. burnetii antigen. Tetracycline, with or without lincomycin or cotrimoxazole, was used in nine patients, and one patient received cotrimoxazole as the sole antibiotic agent. Optimal duration of therapy is unknown. In one patient, relapse followed when treatment was stopped after 18 months. Valve replacement was necessary in five patients, because of hemodynamic problems. Five patients died, and the mean survival is 36 months with a range of five to 66 months. We suggest that Q fever endocarditis is frequently missed, and we recommend clinicians to consider the diagnosis in all cases of culture-negative endocarditis.     

Intramuscular clindamycin for therapy of infective endocarditis: Report of 23 cases and review of the literature

Twenty-three patients with infective endocarditis received intramuscular clindamycin (Cleocin) for treatment. Thirteen had acute Staphylococcus (S.) aureus endocarditis but none had involvement of the aortic valve. Eleven of these 13 infections were heroin-related and involved the tricuspid valve. Twenty-one patients were successfully treated. Two patients with heroin-related S. aureus infection failed to respond to intramuscularly administered clindamycin, but responded to retreatment with methicillin. There have been 34 additional reported cases of endocarditis treated with clindamycin. Although 80 percent of all cases due to staphylococci responded favorably, almost all were heroin-related tricuspid valve infections. In addition 91 percent of cases due to aerobic streptococci responded but, surprisingly, treatment failed in three of four cases of anaerobic endocarditis. Although clindamycin can be useful in streptococcal endocarditis and in some cases of heroin-related S. aureus tricuspid endocarditis, caution should be exercised in its use. It is “less” bactericidal than the penicillins or cephalosporins, and organisms have become resistant during treatment. Furthermore, patients with anaerobic endocarditis have not responded well, and data are not available to recommend administration of clindamycin for acute S. aureus infections engrafted on the aortic or mitral valve.     

Vancomycin therapy of bacterial endocarditis.

Fifteen patients with bacterial endocarditis were treated with vancomycin between 1967 and 1976. The indications for vancomycin therapy were penicillin-cephalosporin allergy in six patients, antibiotic resistant bacteria in six, initial therapy in one and culture-negative endocarditis in two. The causative microorganisms were Staph. epidermidis (four patients), Staph. aureus (two patients), diphtheroids (four patients), viridans streptococci (two patients) and enterococci (one patient). Minimum inhibitory concentrations of vancomycin for these organisms ranged from 0.8 to 3.1 micrograms/ml. The patients received vancomycin for two to 10 weeks (mean five weeks). Cure was achieved in 13 patients, including six with prosthetic valve endocarditis (PVE). Two patients had a relapse of PVE and cultures of blood or heart valve were positive within two months of vancomycin therapy. Vancomycin serum levels did not exceed 50 micrograms/ml, and no serious drug toxicity was encountered in any patient. Three patients had minimal audiogram changes beyond the social hearing range. One patient had mild phlebitis and a rash, and one patient had a transient leukopenia. Vancomycin is an effective nontoxic antibiotic in patients with endocarditis when penicillin or cephalosporin therapy is not appropriate.     

Infective endocarditis in heroin addicts: epidemiological observations and some unusual cases

The total number of cases of heroin-induced endocarditis occurring over a four-year period were reviewed in order to explain an increase in the number of cases in the last year studied (1975). Brown heroin was noted to be used more frequently by addicts during the period of increased incidence. Cultures of "street samples" of brown and white heroin as well as cocaine were obtained in order to elucidate a possible relationship between the increased use of brown heroin and the increased number of endocarditis cases. Despite frequent contamination of both white and brown heroin, none of the common endocarditis-causing pathogens were isolated from the samples. Staphylococcus aureus, the most common etiological agent, frequently resulted in tricuspid endocarditis. That the accepted criteria for tricuspid endocarditis may be present without actual cardiac valve involvement is demonstrated by a most unusual case of hepatic vasculature infection.     

Clinical and microbiologic consequences of amikacin use during a 42-month period

In June 1980, 23% of our Pseudomonas aeruginosa isolates and 53% of our Serratia species were resistant to gentamicin and tobramycin. During a 3 1/2-year period of almost exclusive amikacin usage, we noted a fall in overall resistance of gram-negative organisms to tobramycin and gentamicin from 18.8% and 19.3% to 15.2% and 16.2%, respectively. This fall in resistance was most notable for Escherichia coli, Proteus mirabilis, and Serratia species. During this period there was no increase in amikacin resistance. Age, hospitalization, prior antibiotic therapy, and Foley catheter use were predisposing factors in acquiring amikacin-resistant organisms. Amikacin-resistant gram-negative bacilli were usually sensitive to newer penicillins or cephalosporins.     

Lactobacillemia--report of nine cases. Important clinical and therapeutic considerations

Serious infections due to lactobacilli have been rarely cited. We report our findings in nine recent patients with lactobacillemia. In the combined literature and current experience, endocarditis and sepsis from localized suppuration were the most common clinical syndromes, most frequently arising from prior oropharyngeal infections. Lactobacillus endocarditis showed a predilection for left-sided cardiac involvement (100 per cent) and systemic arterial embolization (55 per cent). The nine clinical isolates were tested for minimal inhibitory and bactericidal concentrations (MICs and MBCs) against five drugs with broad gram-positive spectrums; of note, these organisms demonstrated a high incidence of both unachievable MBCs (64 per cent) and widely disparate (greater than 100 fold) MIC:MBC ratios (38 per cent). This is in accord with observations in Lactobacillus endocarditis of poor in vivo clinical response despite "appropriate" regimens and achievable MICs of the organisms. Bactericidal synergistic studies on two endocarditis isolates indicated that the penicillins plus aminoglycosides may be potentially useful in the treatment of deep-seated Lactobacillus infections when single antimicrobials fail to achieve a cure.     

Clinical and echocardiographic correlations in right heart endocarditis

The echocardiographic findings were correlated with the clinical findings and outcome in 23 patients with tricuspid valve or pulmonary valve endocarditis. There were 15 males and 8 females with a mean age of 33.1 ± 8.4 years. Eighteen patients had tricuspid valve endocarditis, 1 patient had pulmonary valve endocarditis, 3 patients had concomitant mitral valve and tricuspid valve endocarditis, and 1 patient had tricuspid valve and pulmonary valve endocarditis. Twenty of the 23 (87%) patients had a history of intravenous drug abuse. The most common organisms were Staphylococcus aureus (10 of 23 patients or 43%), Streptococcus viridans (5 patients) and Pseudomonas aeruginosa (4 patients). Pulmonary manifestations with septic pulmonary emboli were present in $\text{18}\text{23}$ (80%) patients, and a regurgitant murmur in $\text{16}\text{23}$ (73%) patients. Vegetations on the tricuspid valve or pulmonary valve were detected in all patients who had 2D echo, but they were missed by M-mode echo in 2 patients. Nine of the 23 patients (40%) improved on medical therapy, 5 (21%) expired, and 7 (30%) required surgery (tricuspid valve or pulmonary valve replacement in 3, and tricuspid valve excision without replacement in 4). Conclusions: (1) 11 of 13 patients with persistent infection, multivalvular involvement, fungal or Pseudomonas infection and increasing size of vegetations by echo died or underwent surgery compared to only 1 of 8 patients without these features (P < 0.01). (2) Staphylococcus aureus infection (10 patients) and flail tricuspid valve or pulmonary valve by echo (6 patients) were not predictive of outcome.     

Disseminated infection associated with corticosteroid therapy after transduodenal sphincteroplasty

Treatment with oral prednisolone appears to have precipitated an episode of ascending cholangitis in an asymptomatic 55-year-old patient. He had undergone a Pólya partial gastrectomy, a cholecystectomy and a sphincteroplasty 19, 6 and 2 years earlier, respectively. The cholangitis was complicated by septicaemia with six different enteric organisms including aerobes and anaerobes. He developed liver and lung abscesses, and an indolent Pseudomonas aeruginosa septic arthritis of both hip joints. The patient eventually made a complete recovery, but required surgical replacement of both hips.     

Echocardiographic diagnosis of left atrial myxoma

The presence of a left atrial myxoma in a young woman who presented with mitral valve obstruction was established by echocardiography before surgery. A systematic echocardiographic approach to such a patient is described, by which other diagnostic possibilities, including artifacts, may be eliminated. It is indicated that echocardiography should be performed in patients with suspected obstructive lesions at the mitral valve, unexplained syncope or suspected bacterial endocarditis, as well as in patients who have had atrial myxomas removed since these tumors occasionally recur.     

Fungal endocarditis in non drug-addict patients. 10-year experience

INTRODUCTION AND OBJECTIVES: Fungal endocarditis is an uncommon but serious disease. Five cases of fungal endocarditis, involving non-addict patients, were diagnosed at our hospital in the last 10 years. RESULTS: Causal organisms included Candida albicans (3 patients), Saccharomyces (1 patient) and Torulopsis glabrata (1 patient). The predisposing condition to fungal infection was previous cardiac surgery in four cases (three of them with prosthetic heart valves, and the other patient underwent total surgical correction of Tetralogy of Fallot). No predisposing cause was found in one patient. All patients developed important complications. Three cases underwent cardiac surgery that evolved favorably, and two patients had contraindications for surgery and died from multiorgan septic involvement (overall survival was 60%). CONCLUSIONS: The incidence of fungal endocarditis involving non-addict patients has represented 3% of all cases of infective endocarditis. Even nowadays, fungal endocarditis is a disease with a high mortality and a precocious diagnosis is important to approach surgical treatment and to improve its prognosis.     

Value and safety of cardiac catheterization during active infective endocarditis

Cardiac Catheterization during active infective endocarditis is considered to be hazardous and, consequently, is often delayed. A review was made of experience with 35 patients who underwent Catheterization for severe heart failure (30 patients) and persistent sepsis or recurrent embolization (5 patients) in consideration of surgical intervention. The mean interval from hospital admission to Catheterization was 19 days, and 11 of 35 procedures were performed within 10 days of admission. Precatheterization clinical assessment was incomplete or incorrect in 23 patients. Cardiac Catheterization revealed clinically unsuspected multiple valve involvement in seven patients and documented single valve involvement in six patients with murmurs clinically suggestive of multiple valve endocarditis. In one patient thought to have mitral endocarditis, Catheterization localized the problem to the tricuspid valve. In six patients the study disclosed valve ring abscess and in three it provided anatomic definition of a left to right shunt associated with infection of a ruptured sinus of Valsalva. One additional patient was “cured” of infection by removal of a subclavian catheter fragment. The only complication encountered was transient atrial fibrillation. Catheterization-induced embolization and postcatheterization hemodynamic deterioration did not occur in these 35 patients. It is concluded that cardiac Catheterization yields invaluable hemodynamic and anatomic information and can be performed with minimal risk in patients with infective endocarditis who are being considered for surgery.     

The demonstration of vegetations by echocardiography in bacterial endocarditis: An indication for early surgical intervention

The visualization of vegetations by M-mode echocardiography in patients with infective endocarditis has been suggested to imply a poor prognosis regarding the development of major systemic emboli, congestive heart failure and the need for early surgical intervention. The question of using the finding of vegetations by echocardiography as an indication for surgery is controversial. To answer this question, 30 patients with the clinical diagnosis of endocarditis were studied by echocardiography. In 17 of the 30 (57 per cent) vegetations were present (aortic eight, mitral four, both mitral and aortic five), whereas in 13 (43 per cent) no vegetations were visualized. Infecting organisms were similar in each group; Streptococcus viridans being the most common. The patients with echocardiographically demonstrable vegetations had a higher incidence of congestive heart failure compared to the patients without (14 of 17 versus six of 13, p < 0.05), major emboli (eight of 17 versus two of 13, p = NS) and need for valve surgery (17 of 17 versus two of 13, p < 0.001). Mortality was not significantly different in the two groups (six of 17 versus three of 13, p = NS). Urgent or emergency surgery was required in 16 of 17 patients with vegetations. Thus, the demonstration of vegetations by echocardiography i dentified a subset of patients with more severe disease in whom early operative intervention was required.     

Septicemia due to Xanthomonas species and non-aeruginosa Pseudomonas species: increasing incidence of catheter-related infections

We reviewed 149 episodes of septicemia caused by X. maltophilia and Pseudomonas spp. occurring over a 15-year period. The incidence of septicemia caused by these organisms increased in recent years and was most frequently associated with central venous catheterization. These infections were occasionally complicated by pneumonia or endocarditis, which was often fatal. Although the survival rate was superior to that seen with septicemia caused by other gram-negative organisms, recurrence of infection was significantly more frequent. Removal of central venous catheters is an essential component of therapy of this infection.     

Effect of aerosol immunization with RE 595 Salmonella minnesota on lung bactericidal activity against Serratia marcescens, Enterobacter cloacae, and Pseudomonas aeruginosa.

Intrapulmonary bactericidal activity was measured after mice were given 3 weekly aerosol exposures to acid-hydrolyzed Re 595 Salmonella minnesota. Ten days after their last immunization, mice were challenged with aerolized Serratia marcescens, Enterobacter cloacae, or Pseudomonas aeruginosa. Quantitative bacterial counts in ground lung were obtained immediately after exposure and again 4 hours later. Enhanced bactericidal activity against Serratia marcescens and Enterobacter cloacae was seen in immunized animals, whereas no difference with Pseudomonas aeruginosa was noted. In separate studies, immunization with Serratia marcescens yielded a similar enhancement of lung bactericidal activity. Mucociliary transport, as measured by disappearance of aerosolized Serratia marcescens labeled with phosphorus-32, was identical for both immunized and control animals. Using a standardized in vitro mouse alveolar macrophage phagocytic system, lung washes from animals immunized with Re 595 Salmonella minnesota had significant opsonic activity for Serratia marcescens but not for Pseudomonas aeruginosa.     

Infective endocarditis with negative blood cultures. An analysis of 52 cases.

The clinical records of 52 patients who were diagnosed clinically as having had infective endocarditis despite negative blood cultures have been reviewed. They differed at presentation from patients with positive blood cultures in more frequent receipt of antibiotics prior to culture and more frequent signs of major systemic emboli and congestive heart failure. Response of culture-negative patients with fever to empiric antibiotic therapy was correlated with survival, in that 92 per cent of the patients who became afebrile within the first week of therapy liver, whereas only 50 per cent of those who did not become afebrile lived. Deaths resulted primarily from major systemic emboli and from uncontrollable congestive heart failure due to valvular insufficiency. In 25 cases, valvular tissue was examined histologically. In 15 cases, vegetations were seen and organisms identified; in six cases, only vegetations were seen; and in four cases (16 per cent), the clinical diagnosis of infective endocarditis was not substantiated in the pathologic report.     

Recurrent infective endocarditis: analysis of predisposing factors and clinical features.

To characterize the patient population and clinical features of recurrent infective endocarditis, 117 patients with 142 episodes of infective endocarditis were investigated. Sixty-one (52 per cent) of the total population were drug abusers. Of the 96 who survived the initial episode of infective endocarditis, 58, including 34 drug abusers, were followed for a mean duration of 128 weeks. Recurrent infective endocarditis occurred in 18 of 58 (31 per cent); 14 of 34 (41 per cent) of drug abusers versus four of 24 (17 per cent) of nondrug users (P < 0.05). In addition to drug abuse, prior heart disease and periodontitis were each related (P < 0.05) to recurrence. Patients with ? two risk factors for endocarditis were more likely (P < 0.05) to have a recurrence than those with only one risk factor. Causative organism and site of infection were similar with initial and recurrent infections. Although congestive heart failure complicating aortic and mitral valve infections occurred more frequently in recurrent versus initial infection (15 of 15 versus 43 of 72; P < 0.05), systemic emboli were documented with similar frequency (P > 0.05). Excluding debilitated patients, mortality was greater in those with recurrent versus initial infections (six of 24 versus nine of 96; P < 0.05). Each of three habitual drug abusers who survived insertion of a valvular prosthesis for the initial infection had a recurrence versus none of eight nondrug abusers with prosthetic valves (P < 0.05). Thus, recurrent endocarditis is a commonly encountered and often grave complication of infective endocarditis, particularly among chronic drug abusers.     

Echocardiographic manifestations of valvular vegetations

Eight patients with autopsy or surgically proved valvular vegetations were examined using echocardiography. Five of these patients had lesions on the aortic valve and three had lesions on the mitral valve. The echocardiographic finding in these patients was a non-uniform thickening of valve leaflets which exhibited unrestricted motion. Often the abnormal echoes which produced the thickened valve had a shaggy appearance. In all eight patients the location of the echocardiographic abnormality correlated with the anatomic findings at surgery or autopsy. In one patient the diagnosis of bacterial endocarditis was first suspected following the echocardiographic examination and only subsequently was a heart murmur heard. These findings indicate that echocardiography may play a useful role in elucidating the pathological anatomy of the bacterial endocarditis with vegetation; however, the length of time from the onset of clinical illness to echocardiographic diagnosis remains unknown.     

Serratia marcescens endocarditis: a regional illness associated with intravenous drug abuse.

From 1969 to 1974, 19 cases of Serratia marcescens endocarditis were observed in the San Francisco Bay Area. Seventeen patients were intravenous drug users, and Serratia caused 14% of all addict-associated endocarditis in San Francisco. Serratia strains were nonpigmented and had typical antibiotic sensitivities, except that 9 of the isolates exhibited colonial variation, with each variant having different antibiotic sensitivities. Aortic or mitral valves were involved in 13 patients, and heart failure developed in 9 of these. Twelve patients had embolic episodes to brain, iliofemoral arteries, or lung. Five of 6 patients with tricuspid valvulitis were cured by antibiotics either with (1) or without excision of the valve. All 12 patients with aortic or mitral valvulitis treated medically died; 11 had unremitting sepsis. Aortic valve replacement and antibiotics were effective in 1. Gentamicin combined with either carbenicillin or chloramphenicol was the most effective treatment regimen.