Layne O. Gentry

Plate method for detection of phospholipase activity in Candida albicans

Intracellular phospholipase activity has previously been detected in Candida albicans. A plate method is described which allows rapid detection and measurement of the extracellular activity in a number of clinical isolates. The ratio of colony diameter to diameter of the dense white zone of precipitation around phospholipase positive colonies, (Pz value), correlates with hydrolysis of [14C]phosphatidylcholine by concentrated culture filtrates of selected test isolates. A large variation in phospholipase activity is found between different isolates of C. albicans, however the Pz value is constant for any one isolate regardless of the site from which it is recovered in the patient. Fifty five % of fresh blood isolates are positive and these are also the most potent phospholipase producers. Fifth % of wound isolates and 30% of urine isolates are also positive. A larger sample group must be studied, however, before it can be determined whether these differences are highly significant.

Endogenous Endophthalmitis Among Patients with Candidemia

Thirty-eight patients with fungemia were examined prospectively for development of endophthalmitis. Endophthalmitis was present in 10 of 27 (37%) patients with Candida albicans fungemia. Only one patients with nonalbicans fungemia developed endophthalmitis. Of the preselected factors studied, only hemodialysis and parenteral hyperalimentation correlated with an increased incidence of endophthalmitis. Antibody titers by latex agglutination were of little predictive value for endophthalmitis. Antigen titers by latex agglutination were performed in four cases with endophthalmitis. Antigenemia was demonstrated in three of the four patients, all of whom had negative antibody serologies. Although inconclusive, the preliminary data indicate the test may prove to be of clinical value. Periodic ophthalmoscopic examinations should be considered mandatory in the evaluation of patients with fungemia.

Latex agglutination test for detection of Candida antigen in patients with disseminated disease

A latex agglutination test has been devised which allows detection of a circulating antigen in patients with systemic infection due toCandida albicans, Candida tropicalis andCandida parapsilosis. Latex is sensitized with serum from rabbits immunized with whole heat killedCandida albicans blastoconidia. The active component of this serum is IgG. Control latex, used to differentiate non-specific agglutination, is sensitized with the same dilution of serum from a rabbit without antibody toCandida species. Sera from a number of patient groups were tested. While none of the hundred normal controls had an antigen titer of ⩾ 1∶4, 30 of 33 patients with documented disseminated candida infection had antigen titers of 1∶4 to 1∶32. Two of the 33 gave false negative results, and one caused nonspecific agglutination. In all patients who recovered after antifungal therapy antigen levels returned to within the range found in normal controls.

Surgery in active infective endocarditis.

SUMMARY Controversy persists concerning the role of early surgical intervention in severe infective endocarditis (IE). We therefore reviewed 163 episodes of well-documented IE in which 32 cardiac operations were performed during the active phase of IE. Congestive heart failure (CHF) was the principal indication for surgery in 88% (28/32); systemic emboli, 1/32; and persisting sepsis, 3/32. Staphylococcus and enterococcus were the most common infecting organisms in the operative group (44% and 16% respectively). Surgical mortality (11/32, 37%) did not differ (p > 0.05) from medical mortality (26/131, 20%). All 11 operative deaths occurred in patients moribund prior to surgery, including three with preoperative cardiac arrest. Surgical patients undergoing preoperative cardiac catheterization demonstrated marked CHF: a mean left ventricular end-diastolic pressure of 25.3 mm Hg. The mean cardiac index in 8/11 surgical deaths was lower (p < 0.05) vs surgical survivors: 2.2 1/min/m2 vs 3.2 I/min/m2. Postoperative complications were rare in the 21 surgical survivors. There were no episodes of continued infection, prosthetic dehiscence, or advanced heart block; only one paravalvular leak; and one systemic embolus. These findings emphasize the high medical and surgical mortality in patients with IE, suggest that delayed operative intervention may be a major causative factor resulting in a high surgical mortality, and justify an aggressive surgical approach in patients with valve dysfunction and heart failure. These data indicate that survivors of surgical intervention during active IE have eradication of infection and few postoperative complications.

Perioperative Antibiotic Therapy for Penetrating Injuries of the Abdomen

From 1979 through 1981, 152 patients with penetrating injuries of the intra-abdominal gastrointestinal tract were placed on one of three different perioperative antibiotic regimens in a prospective randomized fashion. The three regimens were A) cefamandole 2 grams every 4 hours, B) cefoxitin 2 grams every 6 hours, and C) ticarcillin 3 grams every 4 hours and tobramycin 1.5 mg/kg every 8 hours. Antibiotics were administered intravenously before and for 48 hours following surgical exploration and repair. The three treatment groups were similar with respect to age, average number of organ injuries, and distribution of organ injuries. Cefoxitin-treated patients experienced uneventful recoveries more often than cefamandole-treated patients (94% vs. 80.3%, p less than 0.05) when the incidence of gram-negative wound infection and intra-abdominal abscess formation was considered, while the number of patients who experienced uneventful recoveries in the ticarcillin-tobramycin group was not statistically different from the other two groups of patients. Bacteroides fragilis was isolated from three of the six abscesses occurring in the cefamandole-treated group, while no anaerobes were isolated from abscesses in patients treated with either of the other two regimens. The results of this study suggest that the most effective perioperative antibiotic regimen for patients with penetrating gastrointestinal wounds should possess activity against both aerobic and anaerobic flora of the bowel.

Intravenous/oral ciprofloxacin versus intravenous ceftazidime in the treatment of serious gram-negative infections of the skin and skin structure

A prospective, randomized, non-blind comparison of sequential intravenous/oral ciprofloxacin with parenteral ceftazidime as treatment for serious infections of the skin and skin structure caused by susceptible gram-negative organisms was conducted. For mixed gram-positive or anaerobic infections, concurrent therapy with vancomycin or anti-anaerobic agents was used. The mean duration of therapy was 25 days for the 32 evaluable ciprofloxacin-treated patients and 19 days for the 19 evaluable ceftazidime-treated patients. Overall response was cure in 24 of 32 (75 percent) ciprofloxacin-treated patients and 11 of 19 (58 percent) ceftazidime-treated patients (0.01 less than p less than 0.05). Ciprofloxacin eradicated 36 of 46 (78 percent) pathogens and ceftazidime 21 of 29 (72 percent) pathogens. Superinfections occurred in nine of 32 (28 percent) ciprofloxacin patients and in two of 19 (11 percent) ceftazidime patients (0.01 less than p less than 0.05). Adverse reactions requiring cessation of therapy occurred in two of 32 (6 percent) ciprofloxacin patients and in one of 19 (5 percent) ceftazidime patients. There was one death in each group; neither was due to the infection or antimicrobial therapy. Chronic infection was a significant risk factor for failure in both groups. Ciprofloxacin was as effective and safe as ceftazidime for serious infections of the skin and skin structure.

Treatment of skin, skin structure, bone, and joint infections with ceftazidime.

The collective experience with ceftazidime in the treatment of skin, soft tissue, bone, and joint infections is presented. Patients were treated with dosages ranging between 25 and 150 mg/kg per day for between five and 42 days. A total of 570 patients with skin and skin structure infections were treated with ceftazidime. Comparative studies, using either cefamandole or tobramycin plus ticarcillin as control drugs, included 239 patients. There were 600 evaluable patients in five categories of skin or skin structure infection: 252 patients had cellulitis, 107 had wound infections, 103 had abscesses, 90 had skin ulcers, and 48 had other miscellaneous infections. Bacteriologic etiologies were gram-negative rods in 303 episodes, gram-positive cocci in 241, anaerobes in 14 episodes, and miscellaneous other organisms in 48 episodes. Overall bacteriologic efficacy was 90 percent in ceftazidime-treated infections and 76 percent in control-treated infections. The clinical efficacy of ceftazidime against infections caused by the gram-positive cocci, particularly Staphylococcus species, was surprisingly good (85 percent) and similar to the efficacy achieved in the cefamandole-treated patients (85 percent). The overall clinical efficacy for ceftazidime was 93 percent. One hundred thirty-four patients with bone or joint infections received ceftazidime. The dosages were similar, but the duration of treatment was the longest in this group. Ceftazidime treatment was compared with standard dosages of tobramycin and ticarcillin in 11 patients. Osteomyelitis was cured in 58 of the 101 patients who received ceftazidime. In five patients, osteomyelitis failed to respond: in two, a resistant Pseudomonas strain emerged; the other three failures were due to persistent bone sequestra. Thirty-eight patients showed improvement. Of those in the tobramycin and ticarcillin group, nine of 10 evaluable patients (90 percent) showed either cure or improvement. The one failure was due to a persistent sequestrum. Thirteen patients with septic arthritis and seven with bursitis were also treated with ceftazidime; the overall cure rate was 75 percent. Adverse reactions to ceftazidime were severe, and the drug was discontinued in 13 of 570 (2.3 percent) patients with skin or skin structure infections and in five of 134 (3.7 percent) patients with bone and joint infections. These data suggest that ceftazidime is effective as monotherapy in the treatment of skin, skin structure, bone, and joint infections, and that it may be more efficacious against staphylococcal infections than predicted from in vitro data.

Subacute bacterial endocarditis due to Actinobacillus actinomycetemcomitans.

Sixteen documented cases of Actinobacillus actinomycetemcomitans endocarditis have been reported in the past 15 years. The characteristic granular growth and the fastidious nature and slow-growing character of this organism decrease the yield of positive blood cultures. Two recently observed cases of subacute endocarditis due to Actinobacillus are reported, one in a patient who required surgical intervention for complications of his disease and the other case associated with an aortic prosthetic valve. The first patient had late embolic complications which are commonly seen with Actinobacillus endocarditis. A review of the literature; including a synoptic table with clinical failures, treatment, and outcome is presented. Unless special care is taken to isolate these slow growing organisms, these cases will be misclassified as culture negative endocarditis.

Use and value of serologic tests for the diagnosis of systemic candidiasis in cancer patients: A prospective study of 146 patients

Sera from 146 cancer patients at risk for disseminated candidiasis were studied prospectively with immunodiffusion (ID), counterelectrophoresis (CEP), and latex agglutination (LA) tests to determine their diagnostic value in the detection of antibodies to theCandida species. Serial serum samples, cultures, and clinical data were obtained after a malignancy was diagnosed. Patients were classified into three groups (I, II, and III) on the basis of cultural, histological, and clinical evidence for superficial (Group I) versus disseminated (Group III)Candida infection. Thirty-two of 78 patients (41%) in Group I had positive ID, CEP, and LA titers. In Group II, those patients lacking histological confirmation of disseminated infection, 16 of 18 (89%) had positive titers. Thirty-six of 50 (72%) in Group III were positive by all three tests. Heavy colonization of the gastrointestinal tract, without evidence of tissue invasion, produced positive test results. Negative serologic tests were encountered in immunosuppressed patients with rapidly progressive candidiasis.C. krusei infections produced specific antibody titers detected by the homologous antigen but not byC. albicans antigen. Stable or decreasing LA titers were correlated with clinical improvement in patients receiving effective antifungal therapy.

Prevalence of Nasal Colonization With Methicillin-Resistant Staphylococcus aureus in Selected Patient Populations

Methicillin-resistant Staphylococcus aureus nasal colonization was investigated in patients arriving for elective cardiovascular surgery, renal patients admitted for arteriovenous graft surgery, and patients transferred to our hospital from other institutions. Renal patients were significantly more likely to be colonized and represent a potential source of MRSA to our institution.