Risk factors for infective endocarditis: oral hygiene and nondental exposures.

BACKGROUND: The risks of infective endocarditis (IE) associated with various conditions and procedures are poorly defined. METHODS AND RESULTS: This was a population-based case-control study conducted in 54 Philadelphia, Pa-area hospitals from 1988 to 1990. Community-acquired IE cases unassociated with intravenous drug use were compared with matched community residents. Subjects were interviewed for risk factors. Diagnoses were confirmed by expert review of medical record abstracts with risk factor data removed. Cases were more likely than controls to suffer from prior severe kidney disease (adjusted OR [95% CI]=16.9 [1.5 to 193], P:=0.02) and diabetes mellitus (adjusted OR [95% CI]=2.7 [1.4 to 5.2], P:=0.004). Cases infected with skin flora had received intravenous fluids more often (adjusted OR [95% CI]=6.7 [1.1 to 41], P:=0.04) and had more often had a previous skin infection (adjusted OR [95% CI]=3.5 [0.7 to 17], P:=0.11). No association was seen with pulmonary, gastrointestinal, cardiac, or genitourinary procedures or with surgery. Edentulous patients had a lower risk of IE from dental flora than patients who had teeth but did not floss. Daily flossing was associated with a borderline decreased IE risk. CONCLUSIONS: Within the limits of the available sample size, the data showed that IE patients differ from people without IE with regard to certain important risk factors but not regarding recent procedures.

Occurrence of De Quervain's tendinitis during pregnancy.

Six women developed De Quervain's tenosynovitis during pregnancy. Onset was never before the fifth month. Two patients also had carpal tunnel syndrome. In two otherwise untreated patients, tendinitis resolved only after discontinuation of nursing. We discuss the possibility of association with hormonal changes occurring during pregnancy.

Staphylococcus aureus endocarditis: clinical manifestations in addicts and nonaddicts.

Data collected from a prospective multicenter study of endocarditis caused by S. aureus were analyzed to contrast the clinical presentation of the disease between a group of 46 intravenous drug addicts and a group of 35 nonaddicts. Two-thirds of the patients in each group were men. The duration of illness before diagnosis was similar (mean, 9.3 days). Intravenous-drug addicts were younger and had less underlying disease (30% versus 80%) than the non-addicts. When first seen, the drug addicts had signs and symptoms of sepsis and pulmonary embolism, but only 40% had pathologic murmurs. Seventy-six percent had evidence of tricuspid valve infection only. Congestive heart failure and neurologic manifestations were uncommon in addicts. Nonaddicts had infection involving predominantly the left side of the heart (14 mitral valves, 8 aortic valves, 4 both aortic and mitral valves) and 80% had underlying medical diseases. Only half of these patients had pathologic murmurs when first examined, but another 30% developed them later. Congestive heart failure, involvement of the central nervous system, and peripheral embolic or septic complications each occurred in over half of the nonaddicts. Eighty percent of these patients had peripheral stigmas of endocarditis. One intravenous drug addict (2%) and seven nonaddicts (20%) died. Six patients required cardiac valve replacement either during or after a course of antibiotics. Outcome was not related to the titer of peak serum bactericidal tests. Endocarditis caused by S. aureus presents as two distinct clinical syndromes depending on the patient population (intravenous drug user or nonaddict) and the location of infection (right-sided or left-sided). The disease is distinguished from endocarditis due to other causes by its acute onset and its fulminant course manifested by a multitude of septic and embolic complications and its ability to cause heart failure. Medical management alone is often successful but in certain subsets of patients, notably those with infection of aortic or multiple valves, early operation may be necessary.

Clinical efficacy of ciprofloxacin therapy for gram-negative bacillary osteomyelitis.

The efficacy and toxicity of ciprofloxacin, an orally administered fluoroquinolone, were evaluated in 24 infections in 23 patients with osteomyelitis caused by aerobic gram-negative bacilli. The diagnosis was confirmed by surgical findings and the results of bone biopsy and culture of bone or deep soft tissue. The aerobic gram-negative bacilli were Pseudomonas aeruginosa (15 isolates), Serratia marcescens (five isolates), Escherichia coli (three isolates), Enterobacter species (three isolates), Proteus mirabilis (one isolate), Pseudomonas fluorescens (one isolate), and Klebsiella pneumoniae (one isolate). Minimal bactericidal concentrations (MBCs) were 1.56 micrograms/ml or less for all but one isolate. Nine infections were polymicrobial, involving aerobic gram-positive cocci or anaerobes in addition to aerobic gram-negative bacilli. Additional antibiotics to which the aerobic gram-negative bacilli were resistant were given when the additional organisms were resistant to ciprofloxacin. Patients received 750 mg of ciprofloxacin twice daily for a mean of 62 days. Peak serum levels of ciprofloxacin were at least threefold higher than the MBCs in 20 of 24 patients. Twenty of 22 infections in which a full course of therapy was completed were without evidence of active disease at one to 17 months posttreatment. A sternotomy wound infection relapsed after eight weeks of therapy with a newly resistant S. marcescens strain, and an infection of a compound fracture relapsed two months posttreatment with a still sensitive P. aeruginosa strain. Toxicity was minimal in most patients: eosinophilia (six patients), nausea (eight patients), mild elevation in transaminase levels (three patients), pruritus (one patient), diarrhea (two patients), thrush (two patients), rash (two patients), and mild leukopenia (one patient). Two additional patients had severe side effects (vertigo in one and acute renal failure in another) that required discontinuation of ciprofloxacin therapy. Overall, ciprofloxacin is a promising agent for the oral treatment of gram-negative bacillary osteomyelitis.

Assessing diagnostic criteria for active infective endocarditis.

A study was performed to describe agreement among experts on their classification of patients, in the absence of information concerning risk factors, as to the presence of infective endocarditis (IE). The study also assessed the clinical characteristics that enabled the experts to determine that a patient had IE. All patients with a discharge diagnosis of IE were identified prospectively from 54 hospitals in the Delaware Valley over a 3-year period. Patients were part of a case-control study of risk factors for IE. Three infectious disease experts independently reviewed abstracted hospital records and classified each of 151 eligible patients as a definite, probable or possible case, or a probable noncase, both based on clinical judgement and using a modified standard definition. Experts were more likely to classify a patient as a definite case of IE on the basis of clinical judgement than by using the modified standard definition. Agreement between reviewers was 92 to 95% when they were distinguishing only probable non-cases from others. Agreement between reviewers on specific categories was lower (40 to 58%). The number of positive blood cultures was a strong predictor of a patient's being classified as a case, as was the type of infecting organism. It is concluded that experts are willing to make a definitive diagnosis of IE on the basis of blood culture information alone. Further supporting evidence, such as the presence of vegetation on an echocardiogram, is needed when blood culture results are ambiguous.

Incidence of infective endocarditis in the Delaware Valley, 1988-1990.

This population-based study aimed to determine the incidence of native, prosthetic, and bioprosthetic valve nosocomial infective endocarditis (IE), and IE associated with the use of injected drugs. Patients with IE during 27 months over the years 1988 to 1990, and residing in any of 6 counties in the Philadelphia metropolitan area were identified. An expert panel reviewed all patients to verify the diagnosis. Incidence rates were estimated after adjustment for failure to recruit and underreporting. Of 853 potential patients, 670 (79%) met the inclusion criteria. The overall incidence rate of IE was 11.6 cases/100,000 person-years (95% confidence interval [CI] 10.8 to 12.4). The rates for specific types of IE were: 4.45 (95% CI 3.97 to 4.94) for community-acquired native valve, 0.94 (95% CI 0.72 to 1.12) for prosthetic valve, 0.94 (95% CI 0.71 to 1.16) for nosocomial, and 5.34 (95% CI 4.80 to 5.87) for IE associated with use of injected drugs. Previous population studies found overall incidence rates of 1.7 to 4 cases/100,000 person-years, similar to our rate for community-acquired native valve IE. Type-specific rates have not been previously reported. The higher overall rate in this study is partly related to the high prevalence of injection drug use in our area.

Anaphylaxis during autologous peripheral blood progenitor cell infusion.

Anaphylaxis has been reported in subjects receiving peripheral blood precursor cell (PBPC) infusions; however the etiologic agent is unclear. Basophils from a PBPC-allergic subject were challenged with each individual component of the stem cell infusion and with recombinant human (rh)DNAse. Histamine release data were compared with those using basophils from control subjects. Histamine release assays were repeated using basophils from a control subject passively sensitized with serum IgE from the patient. Skin testing with bovine DNAse was performed using standard techniques. Basophil histamine release occurred in the patient, but not in controls, with bovine DNAse. No release could be provoked by any of the other components of the infusate; no release could be detected with rhDNAse. Sensitivity to bovine DNAse could be transferred to basophils from a control subject with the serum IgE from the patient. Marked epicutaneous skin test reactivity to bovine DNAse was evident in the patient, but not in control subjects. We conclude that systemic reactions during peripheral blood precursor cell infusions may represent true IgE-mediated anaphylaxis to bovine DNAse in the infusate. Skin testing can detect such sensitivity, and the use of rhDNAse may obviate such reactions.

Distribution of methicillin-resistant Staphylococcus aureus clones among health care facilities in Connecticut, New Jersey, and Pennsylvania. .

A previous surveillance study conducted in 12 hospitals in New York City in 1996 identified a unique multidrug-resistant genetic lineage of methicillin-resistant Staphylococcus aureus (MRSA) that was widespread and accounted for as much as 42% of all the MRSA isolates. The purpose of the study described here was to determine possible geographic spread of this New York clone of MRSA to neighboring states. Single-patient MRSA isolates (258) from 29 health care facilities in Connecticut (CT), New Jersey (NJ), and Pennsylvania (PA) were collected during the calendar year 1998. DNA typing, consisting of fingerprinting of chromosomal macrorestriction patterns generated by SmaI digestion followed by pulsed-field gel electrophoresis (PFGE), identified 22 patterns. PFGE type A, closely related to the PFGE type of the previously identified New York clone, accounted for 154 (60%) of 258 isolates. The clone was detected in all facilities, was predominant in 19 of the 29 health care centers, and accounted for 92% of the MRSA isolates collected in PA. The overwhelming majority of MRSA with PFGE type A was also resistant to erythromycin, ciprofloxacin, and clindamycin. One of the two most common PFGE subtypes detected in the three states sampled (PFGE subtype A1) had an identical PFGE pattern to that of the previously described vancomycin-resistant strain of S. aureus (VISA) recently detected in a hospital in Westchester, NY. The second most frequent MRSA clone with PFGE type E and accounting for 26% (68/258 isolates), also described earlier in the 12 New York City hospitals, was resistant not only to erythromycin, ciprofloxacin, and clindamycin, but also to gentamicin and sulfamethoxazole-trimethoprim as well. The unique multidrug resistance pattern of this second clone and its geographic distribution accounted for the differences observed in the frequency of multidrug resistance among MRSA isolates recovered in the three states. The pandemic Iberian clone recently detected in New York City was not detected among the 258 MRSA isolates recovered in CT, NJ, and PA.

Effects of antibiotics on the mammalian immune system.

Studies on the immune effects of antibiotics are in their infancy. Most currently available data fit into the anecdotal category--there are no standard assays for determination of immune inhibition or enhancement. Most studies were performed in vitro; minimal correlation is made between the mode of action and the intracellular penetration of the test antibiotics, and mechanisms of noted effects are largely unexamined and unexplained. Thus, the observations are frequently contradictory and difficult to interpret. Nevertheless, it has become apparent that certain antibiotics do have potent immunomodulating actions. The clinical impact of such immunomodulation is unknown, since few studies have been performed in patients receiving antibiotics and virtually no studies have examined the effect of antibiotics on the immune system of those at highest risk for sustaining an adverse effect, the immunocompromised patient. Well-planned studies on antimicrobial action, adapting the rapidly expanding knowledge of the immune system currently being generated and utilizing the advances in technology for scrutiny of immune affectors, are badly needed. With a better understanding of the effects of such agents on host cells as well as target cells, it is conceivable that in the future antibiotic therapy will consist of regimens that provide not only optimal anti-infective therapy but also optimal immunomodulating support.

Antibacterial agents in pregnancy.

Except for topical, nonabsorbable agents, any antibiotic chosen for use in pregnancy exposes the fetus as well as the mother to its effects. Therefore, initiation of antimicrobial therapy must be based on clear-cut necessity. Because the physiology of the maternal-fetal unit is complex and ethical consideration of potential fetal harm is pre-eminent, data on safety are derived from animal studies, incidental observations on individual women treated with an agent, or longitudinal tracing of groups of women who required treatment with a particular antimicrobial regimen. Consequently, a rating of absolute safety in pregnancy has never been assigned to any currently available antimicrobial agent. Decades of clinical experience with penicillins, cephalosporins, and erythromycins have documented the pharmacokinetics of these drugs in pregnant women as well as their overall safety for the fetus. These classes of drugs are those most favored for use in pregnancy for susceptible infections. Although aminoglycosides have known toxic effects on the fetus, they are safe to use if serum levels are carefully monitored in the mother. Agents in the quinolone, sulfonamide, and tetracycline categories should be avoided unless maternal necessity for their use justifies the exposure of the fetus to their toxicity. Both clinical and experimental data are very limited on the newer agents, such as the new macrolides, azithromycin and clarithromycin. The first-line agents for the treatment of TB (i.e., INH, rifampin, and ethambutol) are considered safe in pregnancy, but in the era of multidrug-resistant mycobacterial isolates, agents with known or suspected fetal toxicity may need to be used.

Value of examination for fecal leukocytes in the early diagnosis of shigellosis.

Fecal specimens from 101 patients with diarrhea were cultured and also examined with methylene blue for leukocytes. Thirty-six patients had leukocytes in their stools and 29 had culture-proven shigellosis. The sensitivity of fecal leukocytes in shigellosis was 95% (19/20) when cup specimens were obtained, and 44% (4/9) when swab or diaper specimens were examined. Only 45% of the patients with shigellosis who provided cup specimens had grossly bloody dysentery. Twelve other patients had fecal leukocytes but no demonstrable invasive bacterial pathogens. Methylene blue examination was useful in identifying motile trophozoites of Giardia lamblia and eggs or larvae of other heavy intestinal paraistic infections. Among patients with naturally-acquired acute diarrhea, methylene blue examination of stools for leukocytes is much more sensitive than examination for blood in predicting a positive culture for Shigella spp. It is also of value in detecting parasites.

Host defense mechanism in the pathogenesis of UTI and UTI in immunocompromised patients.

Defects in the immune system determine the clinical manifestations and severity of urinary tract infections (UTI) and the rates of complication but they only have an indirect role in influencing susceptibility to infection. The rates of UTI in diabetics, renal transplant, recipients, neutropenic patients, and patients with AIDS are primarily determined by the degree and duration of urinary tract manipulation and the higher perineal prevalence of potential pathogens that result from frequent hospitalization and antimicrobial use. Prompt recognition and treatment of established infections is critical to prevent life-threatening complications (e.g. bacteremia, emphysematous pyelonephritis) but routine screening for asymptomatic bacteriuria is indicated only in kidney recipients less that 3 months post-transplantation.

Urinary tract infection in the impaired host.

In general, defects in phagocytosis and in humoral or cellular immunity do not appear to predispose to the acquisition of UTI but do influence the clinical manifestations and the severity, microbiology, and complications of infection once it is established. The incidence of UTI in immunosuppressed patients other than diabetics or renal transplant recipients is not higher than the incidence in nonimmunosuppressed individuals. The higher frequencies of infection seen in diabetics and in renal transplant recipients correlate best with the duration of bladder instrumentation rather than with glycosuria or immunosuppressive regimen. Neutropenia blunts the clinical manifestations of UTI and predisposes to bacteremia. Use of broad spectrum antibiotics results in alterations in indigenous flora, promotes urinary infections with resistant nosocomial pathogens, and predisposes to fungemia with hematogenous seeding of the urinary tract. Routine screening for detection of asymptomatic bacteriuria and prompt institution of antimicrobial therapy is indicated only in renal transplant recipients within 3 months of their surgery and not in any of the other diseases discussed.

A controlled study of endemic sporadic diarrhoea among adult residents of southern Brazil.

The aetiology of sporadic summer diarrhoea and enterotoxin (LT) antibody titres was studied among 43 adult patients in southern Brazil who had an acute, untreated diarrhoeal illness and 43 age- and sex-matched controls from the same area. A potential pathogen was identified in 33 of 34 patients and in 17 of 43 controls (p less than 0.01). 10 Shigella, one invasive Escherichia coli, one Salmonella and one Entamoeba histolytica were identified in 17 patients with inflammatory diarrhoea (faecal polymorphonuclear neutrophil leucocytes (PMN) present). In the other four only enterotoxigenic strains of E. coli were identified. Among 26 patients with non-inflammatory (no faecal PMN) diarrhoea, heat-stable (ST) toxin-producing coliforms were the most common pathogens isolated (27%). Heat-labile (LT) toxin-producing coliforms or serological rises to LT were seen in five patients, Strongyloides larvae in five, Giardia lamblia trophozoites in four and an LT-producing Salmonella in one. No pathogen was found in 10 patients with non-inflammatory diarrhoea. Among 43 controls, 11 LT coliforms, two Shigella and two Strongyloides larvae were found. 40 of 41 controls had detectable serum anti-LT antibody. A single ST-producing E. coli was found in one other control. No pathogen was identified in 26 controls. No rotaviruses or Norwalk-like viral agents were seen by direct or immune electron microscopy of stool filtrates. While LT-producing E. coli are frequently associated with endemic summer childhood diarrhoea in southern Brazil and are recognized causes of travellers' diarrhoea, this study shows that they are often carried asymptomatically by adults living in this region.(ABSTRACT TRUNCATED AT 250 WORDS)

Combination antimicrobial therapy for Staphylococcus aureus endocarditis in patients addicted to parenteral drugs and in nonaddicts: A prospective study.

Single (nafcillin for 6 weeks) and combined (nafcillin for 6 weeks plus gentamicin for 2 weeks) drug regimens were compared in two separate multicenter prospective randomized trials. Forty-eight parenteral drug addicts and 30 nonaddicts with clinically and bacteriologically documented Staphylococcus aureus endocarditis were studied. In the addicts, combined therapy effected a more rapid mean clinical response (defervescence and normalization of leukocyte count) and a reduced duration of bacteremia in patients with right-sided endocarditis. In the nonaddicts, combined therapy effected more rapid clearance of bacteremia, but was associated with a higher incidence of azotemia. The addition of gentamicin did not alter morbidity or mortality in either group.

Comparative pharmacology of cefaclor and cephalexin.

Two cephalosporin antibiotics, cefaclor and cephalexin, were administered orally to healthy, adult male volunteers for comparison of their pharmacological properties. In doses of 250 mg orally, cefaclor produced a peak serum concentration of 6.01 +/- 0.55 (standard deviation [SD]) mug/ml compared with 9.43 +/- 2.36 mug/ml for cephalexin (P < 0.01). The half-lives were 0.58 +/- 0.07 (SD) h and 0.80 +/- 0.12 (SD) h, and elimination constants were 1.22 +/- 0.15 and 0.88 +/- 0.13 h(-1) for cefaclor and cephalexin, respectively (P < 0.001). Neither drug showed accumulation over the dosing period, and both were well tolerated.

In vitro susceptibility studies with cefaclor and cephalexin.

The in vitro activity of cefaclor and cephalexin against clinical isolates of four bacterial genera was compared. Both agents had a similar range of activity, but cefaclor was significantly more active by weight than cephalexin for most isolates tested.

Factors influencing the pathogenesis and prevention of infective endocarditis.

It seems appropriate in a symposium dedicated to the examination of septicemia, that one of the topics for discussion should be the examination of the factors which allow circulating bacteria to adhere to intracardiac or vascular endothelium. In the last 10-12 years our understanding of the pathogenesis of this disease has increased markedly. This can be attributed to a large extent to the development by Dr Freedman and hist colleagues at Yale of reproducible, simple, inexpensive animal model of infective endocarditis. The purpose of this discussion will by to summarize studies aimed at helping to explain why bacteria stick to cardiac valves, what forms the stimulus for vegetation propagation, and some new idea for possible prevention of this event.

Urinary excretion of Tamm-Horsfall protein in elderly women.

The incidence of urinary tract infection is higher in the geriatric population than in younger adults despite the exclusion of patients with known risk factors. Tamm-Horsfall protein, a renal glycoprotein excreted in urine, may constitute a natural defense mechanism against ascending urinary tract infection by binding mannose-sensitive fimbriated microorganisms. We hypothesized that the quantity of Tamm-Horsfall protein excreted is decreased in the elderly. Native aggregated Tamm-Horsfall protein was measured in urine samples from 24 young women (group 1, mean age 33 years) and 47 female nursing home patients (group 2, mean age 84 years) using enzyme-linked immunosorbent assay techniques. Another 16 elderly women (group 3, mean age 85 years) had active urinary tract infection. The aggregated Tamm-Horsfall protein was then disaggregated by dilution and quantified. Significant differences in mean urinary disaggregated Tamm-Horsfall protein concentrations were found between groups 1 (64.22 mg./l.) and 2 (35.07 mg./l.), and between groups 1 and 3 (34.71 mg./l.), respectively. In contrast, mean aggregated Tamm-Horsfall protein levels were significantly higher in group 2 (1.56 mg./l.) than in group 1 (0.92 mg./l.) or group 3 (0.97 mg./l.). Our studies show that urinary disaggregated Tamm-Horsfall protein concentration is decreased in the elderly, and that aggregated Tamm-Horsfall protein is increased compared to younger adults. The aggregated Tamm-Horsfall protein concentration is decreased in the elderly during episodes of urinary tract infection.