Rhinocerebral mucormycosis: premortem diagnosis and therapy.

The diagnosis of rhinocerebral mucormycosis is most often made at autopsy. We report a series of nine patients in whom the diagnosis was established premortem. Six of the patients had underlying diabetes mellitus and three had acute leukemia. Facial or ocular pain was the complaint found in all patients, and frequently was the initial symptom. The diagnosis was established by examination and culture of infected tissue obtained by biopsy. In seven patients, identification of hyphal elements in smears of biopsy material allowed the immediate institution of amphotericin B therapy. Four of the seven patients treated with amphotericin B survived. All surviving patients had underlying diabetes mellitus and had undergone surgical debridement. Early diagnosis leading to immediate institution of appropriate therapy is most important for survival of patients with mucormycosis.

Use of antimicrobial agents in a university teaching hospital. Evolution of a comprehensive control program.

A comprehensive control program for utilization of anti-microbial agents in a large tertiary university teaching hospital regulates both dosage and duration of therapy and requires the prior approval of an infectious disease specialist for utilization of restricted antimicrobial agents. Benefits of the program include more cost-effective antimicrobial therapy and increased physician education in the use of these drugs. Gross savings in pharmacy costs for antibiotics during the first year of the program (1985) amounted to +483,032 for an average monthly savings of +40,252. Gross savings for 1986 were +211,786 with monthly savings of +17,648. The control of the use of one agent may lead to overuse of another agent. Antimicrobial prescribing patterns of physicians are quickly influenced by changing regulations of the program. An ongoing surveillance and review program of in-hospital utilization of antimicrobial agents is necessary to maintain effective and flexible controls.

Central nervous system infections in the elderly.

Review of records of patients aged 65 years and older admitted to The Mount Sinai Hospital, New York, NY, during the period from 1970 through 1985 revealed 57 episodes of central nervous system infections, including 50 meningitides, 5 brain abscesses, 1 subdural empyema, and 1 epidural abscess. Predisposing conditions were present in 17 patients with meningitis, and concurrent infections occurred in 19 patients. Streptococcus pneumoniae accounted for 43% of all isolates; 25% were gram-negative organisms. Of the patients in this sample, fever was present in 100%, meningismus was present in 58%, and change in mental status was present in 86%. Sixty-five percent of patients with meningitis survived; increased mortality was associated with altered mental status, inappropriate initial antibiotic therapy, and hypoglycorrhachia. Delay in diagnosis, underlying disease, and bacteremia did not significantly alter outcome. All patients with focal infections presented with localizing signs and all survived.

Comparative toxicities of third-generation cephalosporins.

Data on the adverse effects experienced by 2,539 patients who received ceftazidime were compared with adverse effects reported with cefoperazone, cefotaxime, ceftizoxime, and moxalactam. There were 216 such reactions among the ceftazidime-treated patients; 158 patients (6.2 percent) had reactions that were possibly or probably drug-related. The clinical and laboratory safety profile of ceftazidime in regard to renal, hepatic, hematopoietic, and hemostatic parameters compared favorably with that of other third-generation cephalosporins. An increased serum creatinine level was observed in 0.8 percent of ceftazidime-treated patients, an increased blood urea nitrogen level in 1.6 percent, hepatic abnormalities in approximately 6 percent, diarrhea in 1.3 percent, pseudomembranous colitis in 0.12 percent, increased prothrombin time in 0.5 percent, and clinical bleeding in none. The incidence of colonization (3.8 percent) and superinfections (3 percent) associated with ceftazidime therapy was comparable to rates with other agents in this class.

Bloodstream infections in the elderly.

PURPOSE: Bacteremia in the elderly is associated with a different clinical course and a higher mortality rate when compared with that in younger age groups. In order to examine these issues in the aged, we reviewed the clinical course and factors involved in the outcome of 100 episodes of bloodstream infections in patients over 65 years of age. PATIENTS AND METHODS: The hospital records of all patients over 65 years of age at The Mount Sinai Hospital with a positive blood culture result during the period October 1984 to October 1986 were reviewed. Place of residence before hospital admission, site of acquisition of infection, source of bloodstream infection, and microorganism were analyzed. Antimicrobial therapy was defined as appropriate if initial therapy included one agent to which the isolate was sensitive, or inappropriate if the isolate was resistant. The following factors affecting survival were analyzed: age, sex, underlying diseases, clinical parameters on admission, white blood cell count, mental status, source of infection, microorganism isolated, antibiotic toxicity, and appropriate versus inappropriate antibiotic therapy. RESULTS: Most patients were female (63 percent), were febrile (90 percent), had an altered mental status (52 percent), and had a neutrophilic response (61 percent). Eighty-three percent of patients were admitted from the community (home), 14 percent were from long-term-care facilities, and 3 percent were transferred from other hospitals. Fifty percent of infections were nosocomial, and 44 percent were community (home and nursing home)-acquired. Gram-negative organisms accounted for 60 percent of isolates, with Escherichia coli (22 percent) and Klebsiella species (11 percent) predominating; 30 percent were gram-positive organisms, with Staphylococcus aureus (13 percent) and Streptococcus faecalis (10 percent) the most common. The overall survival was 60 percent; the survival rate was 65.8 percent for community-acquired (home) bacteremia, 75 percent for nursing home-acquired bacteremia, and 52.8 percent for hospital-acquired bacteremia. Survival for gram-negative isolates was 65 percent, versus 51.7 percent for gram-positive isolates. Survival was greatest in patients whose source of bacteremia was either the genitourinary tract (70 percent) or an intravascular device (78 percent) and poorest in patients with lower respiratory tract source (42 percent); all three patients with endocarditis died. Increased survival was observed in patients treated with appropriate antimicrobial agents regardless of age, source of infection, or bloodstream isolates.(ABSTRACT TRUNCATED AT 400 WORDS)

Tuberculosis in liver transplant patients.

Tuberculosis has been increasing especially in urban areas and in immunosuppressed patients; however, the incidence and factors associated with tuberculosis in OLT patients are unknown. Five of 550 patients who underwent OLT at the Mount Sinai Medical Center during a 5-year period were noted to have tuberculosis. The mean age of the patients was 49.2 years; there were 3 males and 2 females and 3 were foreign born. One of 5 had a prior history of tuberculosis. Tuberculin skin tests performed before transplant revealed 1 positive and 2 anergic reactions. The preoperative chest x-ray revealed apical fibrosis in 2 patients and bilateral apical disease with a nodule in 1 patient. Tuberculosis developed from 2 to 57 months after surgery in 4/5 patients. One had miliary lesions of the peritoneum discovered at the time of OLT. One patient had recent contact with a patient with pulmonary tuberculosis. At presentation, fever was present in 4 of 5 patients, pulmonary lesions in 3 patients, meningitis in 2; during hospitalization, 1 had a liver abscess and disseminated intravascular coagulation and peripheral gangrene. Lymphocytosis was noted in the pleural (1), peritoneal (1), and cerebrospinal fluid (1). Acid-fast smears were positive in bronchoalveolar lavage fluid (1), peritoneal isolates (1), and liver biopsy (1). All patients had positive cultures for Mycobacterium tuberculosis. These isolates were all sensitive to isoniazid, streptomycin, rifampin, ethambutol, and pyrazinamide. Four of 5 patients were treated with isoniazid and rifampin, 2 received pyrazinamide, 2, amikacin, 2, ofloxacin, and 2, ethambutol. Three of 5 patients are doing well on antituberculous therapy and 2 expired with tuberculosis as the cause of death. In OLT patients with unexplained fever, tuberculosis including extrapulmonary and disseminated disease should be considered since the mortality rate is very high. Liver transplantation can be performed in the presence of active peritoneal tuberculosis with the use of judicious antituberculous therapy. The role of preventive therapy is controversial, though use in certain high risk patients is suggested.

Tuberculosis in orthotopic liver transplant patients: increased toxicity of recommended agents; cure of disseminated infection with nonconventional regimens.

BACKGROUND: Because increased hepatotoxicity was observed with first line antituberculous agents using four drug standard induction therapy in orthotopic liver transplant patients, we evaluated the efficacy and adverse effects of a novel continuation regimen for the treatment of tuberculosis in orthotopic liver transplant patients at a University Hospital in New York City. METHODS: The hospital records of all patients who were referred to Mount Sinai Hospital (n=924) and who underwent orthotopic liver transplant between September 1988 and May 1998 were reviewed. Data were collected from patient records. Nine orthotopic liver transplant patients (0.97%) developed tuberculosis over a 9.5-year period. A total of seven of nine (78%) patients had disseminated tuberculosis including two patients with meningitis. All mycobacterial isolates were sensitive to isoniazid, rifampin, pyrazinamide, and ethambutol. Standard induction therapy with three or four drugs was given for 2 months (mean). Hepatotoxicity related to the standard induction regimen developed in five of six (83.3%) patients. Liver biopsy during induction therapy revealed drug induced hepatitis in five of six (88%) patients and rejection in three of six (50%) patients. Continuation regimens consisted mainly of ethambutol and ofloxacin; mean length of therapy 9 months. RESULTS: Overall mortality was 33.3% (three of nine patients) over a 4.5-year follow-up period. Tuberculosis associated mortality was 22.2%. One patient died before therapy, another died with concomitant bacterial sepsis during induction therapy. Six of seven patients are alive and disease free. One patient died of recurrent hepatitis C and graft failure without evidence of tuberculous infection at death. Another patient retransplanted for chronic rejection, remains disease free at 1 year. The mean follow-up for six patients that completed treatment was 3.75 years (2.5-5.3 years). Six patients are free of tuberculosis. CONCLUSIONS: Our experience reveals that orthotopic liver transplant patients have poor tolerance for conventional therapy due to inherent toxicity of these agents and their concomitant bouts of organ rejection. Our nonconventional therapy yielded remarkably good results in that six patients, all with disseminated disease, were well after mean 3.5 years of follow-up. Consideration should be given to this novel follow-up therapy in patients without cavitary pulmonary disease who develop hepatotoxicity during induction.

Clinical pharmacokinetics of antibacterial drugs in the elderly. Implications for selection and dosage.

A review of the clinical pharmacokinetics of antibiotics in the healthy elderly reveals that for most compounds a decrease occurs in renal clearance (associated with age-related decreases in renal function), as well as a prolonged half-life and increased area under the plasma concentration-time curve. These changes are amplified in the sick infected elderly. It is important that the treating physician be aware of the potential side-effects of antimicrobial agents, and whenever possible choose those which are associated with the least adverse effects. Individual patient variability, including underlying diseases and other prescribed medications, must be taken into account when dosage is selected. beta-Lactam compounds have a remarkable safety record: specifically in the elderly, their therapeutic/toxic ratio is much higher than that observed with aminoglycosides. Regimens for this class of drugs in the elderly should maintain antibiotic concentrations above the minimum inhibitory concentrations for maximum efficacy. In the treatment of elderly patients, it is suggested that dosage and interval be based on estimated or measured creatinine clearance. Usually, for drugs that are excreted primarily by the kidney (i.e. amino-glycosides, beta-lactams and quinolones), dosage intervals must be increased when there is an associated fall in creatinine clearance. The pharmacokinetic parameters suggest that as an alternative to increasing dosage interval the usual dose may be decreased, but further studies are necessary for confirmation.

Hemophilus aphrophilus endocarditis: review of 23 cases.

A case of bacterial endocarditis caused by Hemophilus aphrophilus is described, and 22 previously reported cases are reviewed. Eleven patients died and 12 survived; comparison of these two groups reveals that the patients who died were in the older population. The male/female ratio was 3.6:1. The organism was difficult to identify but had a wide range of in vitro bacteriologic sensitivities. This type of endocarditis is frequently associated with emboli and congestive heart failure; each occurred in 9 of 11 fatal cases and 3 of 12 nonfatal cases. Among the nonfatal cases, two patients had both emboli and congestive heart failure, requiring aortic valve replacement despite their precarious clinical condition. Initial drug therapy before results of antibiotic sensitivity tests are known should consist of penicillin combined with streptomycin. When emboli or congestive heart failure appears in Hemophilus aphrophilus endocarditis, early surgical intervention with valve replacement is indicated.

Study of a needleless intermittent intravenous-access system for peripheral infusions: analysis of staff, patient, and institutional outcomes.

OBJECTIVE: To assess the effect on staff- and patient-related complications of a needleless intermittent intravenous access system with a reflux valve for peripheral infusions. DESIGN: A 6-month cross-over clinical trial (phase I, 13 weeks; phase II, 12 weeks) of a needleless intermittent intravenous access system (NL; study device) compared to a conventional heparin-lock system (CHL, control device) was performed during 1991 on 16 medical and surgical units. A random selection of patients was assessed for local intravenous-site complications; all patients were assessed for the development of nosocomial bacteremia and device-related complications. Staff were assessed for percutaneous injuries and participated in completion of product evaluations. A cost analysis of the study compared to the control device was performed. SETTING: A 1,100-bed, teaching, referral medical center. PATIENTS AND STAFF PARTICIPANTS: 594 patients during 602 patient admissions, comprising a random sample of all patients with a study or control device inserted within a previous 24-hour period on study and control units, were assessed for local complications. The 16 units included adult inpatient general medicine, surgical, and subspecialty units. Pediatrics, obstetrics-gynecology, and intensive-care units were excluded. All patients on study and control units were assessed for development of nosocomial bacteremia and device-related complications. All staff who utilized, manipulated, or may have been exposed to sharps on study and control units were assessed for percutaneous injuries. Nursing staff completed product evaluations. INTERVENTION: The study device, a needleless intermittent intravenous access system with a reflux valve, was compared to the control device, a conventional heparin lock, for peripheral infusions. RESULTS: During the study, 35 percutaneous injuries were reported. Eight injuries were CHL-related; no NL-related injuries were reported (P=.007). An evaluation of 602 patient admissions, 1,134 intermittent access devices, and 2,268 observed indwelling device days demonstrated more pain at the insertion site for CHL than NL; however, no differences in objective signs of phlebitis were noted. Of 773 episodes of positive blood cultures on study and control units, 6 (0.8%) were device-related (assessed by blinded investigator), with no difference between NL and CHL. Complications, including difficulty with infusion (P<.001) and disconnection of intravenous tubing from device (P<.001), were reported more frequently with CHL than with NL. Of nursing staff responding to a product evaluation survey, 95.2% preferred the study over control device. The projected annual incremental cost to our institution for hospitalwide implementation of NL for intermittent access for peripheral infusions was estimated at $82,845, or $230 per 1,000 patient days. CONCLUSIONS: A needleless intermittent intravenous access system with a reflux valve for peripheral infusions is effective in reducing percutaneous injuries to staff and is not associated with an increase in either insertion-site complications or nosocomial bacteremia. Institutions should consider these data, available institutional resources, and institution-specific data regarding the frequency and risk of intermittent access-device-related injuries and other types of sharps injuries in their staff when selecting the above or other safety devices.

Antimicrobial activity in vitro of cefaclor, a new oral cephalosporin.

The antimicrobial activity of cefaclor, a new orally administered cephalosporin derivative, was studied in vitro against a variety of Gram-positive and Gram-negative clinical isolates. Both penicillin-resistant and penicillin-susceptible strains of Staphylococcus aureus were susceptible to cefaclor, with mean MICs of 1.44 and 0.93 microgram/ml, respectively. However, the MBC for penicillin-resistant S. aureus was higher than that for the penicillin-susceptible strains. All strains of Streptococcus pyogenes, Streptococcus viridans, and Streptococcus pneumoniae tested were highly susceptible to cefaclor; all strains of Streptococcus faecalis were highly resistant to cefaclor. Strains of Escherichia coli, Klebsiella sp., Proteus mirabilis, and Hemophilus influenzae were susceptible to cefaclor. Eighty per cent of strains of H. influenzae were inhibited by 5 micrograms/ml of cefaclor. Most strains of Enterobacter sp., indole-positive Proteus, Pseudomonas sp., and Serratia sp. were resistant to cefaclor.

Pharmacokinetic properties of mezlocillin in ambulatory elderly subjects.

Twelve healthy ambulatory elderly subjects (mean age, 73-78 years) randomly received either a 4-g or 5-g dose of mezlocillin intravenously. One week later the regimen was repeated and patients crossed over to the other dose. Peak serum concentrations were 165 mg/L and 281 mg/L for the 4-g and 5-g doses, respectively. For both doses, differences in t1/2 beta (1.32 hr vs 1.13 hr), AUC (275 mg.hr/L vs 403 mg.hr/L), CL (207 mL/min vs 174 mL/min), CLR (59 mL/min vs 45 mL/min), CLNR (152 mL/min vs 130 mL/min) were not statistically significant. The differences in Varea (22.4L vs 168.8L, P less than or equal to .01) and Cmax (216.6 mg/L vs 317 mg/L, P less than or equal to .05) were statistically significant. Comparison with pharmacokinetic parameters obtained in younger subjects following the 5-g dose reveals that in the elderly the AUC, Varea, and CLNR are higher whereas the CL and CLR are lower. The elderly demonstrated an increase in nonrenal clearance compared with young subjects that is not fully compensatory. The increased AUC in the elderly group suggests that clinical studies examining mezlocillin doses and dose intervals in the treatment of serious infections are warranted in infected elderly patients.

Pharmacologic studies with cefaclor, a new oral cephalosporin.

Cefaclor, a new oral cephalosporin, was administered to 18 normal human volunteers in either single or multiple doses of 250 and 500 mg. Mean serum concentrations of 6.09 and 12.8 microgram/ml were achieved 1 hour after single oral doses of 250 and 500 mg, respectively. The serum concentrations declined rapidly and no drug was detected at 4 hours. Very high concentrations of cefaclor were found in urine during the first 8 hours after ingestion of the drug. Forty-three per cent of the total dose was excreted in urine during the first 8 hours. There was no accumulation of drug in serum during the multiple-dose studies.

Pharmacokinetics of aztreonam in healthy elderly and young adult volunteers.

Aztreonam is a monobactam exhibiting an antibacterial spectrum similar to that of the aminoglycosides, with activity against aerobic gram-negative bacilli, and is the only related drug that may be given to patients hypersensitive to beta-lactams. The pharmacokinetics of aztreonam were compared in two groups of healthy volunteers. The young group comprised 10 adults between the ages of 18 and 30 years, and the elderly group included 10 adults older than 65 years of age. The two groups each received two doses (1 and 2 g) aztreonam, separated by 1 week. Although the mean peak serum concentrations of aztreonam for the two groups were similar, there were differences in other pharmacokinetic parameters. For example, for the 2-g dose the mean half-life (1.8 +/- .51 versus 3.1 +/- .9 hour), and area under the curve (AUC) (294.42 +/- 64.08 versus 469.01 +/- 144.02 micrograms x hour/mL per 1.73 m2) were less for the younger group compared with the elderly group. The mean total body clearance of aztreonam was greater for the younger than the elderly group. The results were similar to the pharmacokinetic parameters derived from the 1-g dose. These results mirror the lower creatinine clearances and higher serum creatinine levels found in the elderly group. The data suggest that lower doses of aztreonam given at less frequent intervals may be appropriate in the elderly population.

Cefaclor revisited.

OBJECTIVE: This paper describes the rationale for choosing cefaclor for the management of respiratory tract infections. BACKGROUND: Since 1979, cefaclor has established a record of efficacy in the management of respiratory tract infections. Factors contributing to the efficacy and tolerability of this drug include its molecular stability, activity against the most prevalent gram-positive and gram-negative respiratory tract pathogens, rapid absorption, >90% bioavailability, and good penetration into respiratory mucosa. After 2 decades of widespread use, this agent remains clinically effective in patients with respiratory tract infections, making it competitive with other cephalosporins and with macrolides and fluoroquinolones, including many newer agents used for respiratory tract infections. Cefaclor extended-release tablets, the newest formulation, retain the positive efficacy and tolerability attributes of immediate-release cefaclor, varying mainly in the rate of dissolution. The approved indications for extended-release cefaclor include bacterial bronchitis, pharyngitis, and skin infections. METHODS: A MEDLINE search showed that the few adverse effects related to therapy with cefaclor are usually minor and transient and that drug-drug interactions involving cefaclor are rare. CONCLUSIONS: Multiple clinical trials have shown that extended-release cefaclor in 375-mg and 500-mg doses BID demonstrates tolerability and efficacy comparable to those of immediate-release cefaclor 250 mg TID. Extended-release cefaclor is indicated for BID dosing, which should encourage greater compliance.

Patient survival factors in paranasal sinus mucormycosis.

Analysis of 170 cases of paranasal sinus mucormycosis collected from the literature and 9 cases of our own revealed a 50% mortality for this disease. When analyzed according to decade, survival has increased to 70% in the cases reported from 1970-1979. There were no significant differences between the survivors and the fatalities when evaluated according to age, sex, laterality, or radiographic findings. There was a markedly poorer prognosis for those patients with hemiplegia, facial necrosis, and nasal deformity. The underlying disease was an important determinant of survival: 75% of patients with no systemic disease, 60% of diabetics, and 20% of patients with other disorders survived. Surgical debridement or radical resection and the use of amphotericin B significantly increased survival. Their combination further enhanced survival, especially in the diabetic.

Malignant external otitis. Comparison of monotherapy vs combination therapy.

Twenty patients with adult-onset diabetes mellitus and malignant external otitis (MEO) were treated at the Mount Sinai Medical Center, New York, over a seven-year period (August 1976 to October 1983). A retrospective analysis compared patients who received an antipseudomonal cephalosporin as monotherapy (group A) with those who received conventional antipseudomonal therapy (group B). Pseudomonas aeruginosa was isolated in all patients. Differences (group B less than group A) included insulin dependence, underlying vascular disease, total number of cranial nerve palsies or paresis, and surgical procedures. The overall clinical outcome was similar in both groups; 64% of patients in group A (7/11) and 70% in group B (7/10) were cured at a follow-up period of five to 57 months. A more favorable outcome was found in patients with less extensive infection in both groups. Monotherapy compared favorably with conventional antipseudomonal therapy for the treatment of patients with MEO and moderate infection.

Infectious diseases in the elderly: an overview.

The elderly represent the fastest growing portion of the population. Aspects of the normal aging process combined with chronic diseases place the elderly at increased risk for infection. This overview will discuss the most common infectious diseases in the elderly and some approaches to the prevention and treatment of these infections.

Sensitive indicators of inorganic mercury toxicity.

Forty-two workers from a chemical plant producing inorganic mercury compounds were evaluated for neurologic, nephrotic, and ophthalmologic toxicity. Despite elevated blood and urinary mercury levels, routine clinical testing such as physical examination, blood chemistries, and urinalysis were generally normal. These findings from the routine examination are in contrast to the complaints of neuropsychological symptoms, elevated urinary n-acetyl B-D-glucosaminidase (NAG) levels, decreased motor nerve conduction velocities, and the presence of lenticular opacities on slit-lamp examination that were found, when organ systems known to be affected by mercury were targeted. More sensitive but objective indicators of toxicity need to be included in routine medical screening so as to help diagnose the etiology of neuropsychological symptoms and prevent long-term sequelae in workers exposed to mercury.

Bacterial sinusitis.

Sinusitis may occur secondary to infectious agents, allergens, or pollutants. Bacteriologic studies carried out from sinus punctures revealed that Streptococcus pneumoniae and Hemophilus influenzae are the most common bacterial pathogens isolated. Staphylococcus aureus and Streptococcus pyogenes are not uncommon pathogens. Complications of sinusitis, including orbital cellulitis, usually are due to infection with Staphylococcus aureus and H influenzae. The recent increase in certain areas of the country of beta-lactamase-producing strains of H influenzae is noted. When the etiology remains to be determined in the patient with acute bacterial sinusitis, initial therapy with an oral cephalosporin seems warranted.