Bacterial interference induced in embryonated eggs by staphylococci.

Studies of experimental infections in embryonated eggs demonstrated that prior allantoic infection with avirulent staphylococci afforded significant protection against subsequent challenge with virulent strains. All strains of coagulase-positive and coagulase-negative staphylococci tested that were relatively avirulent for embryonated eggs were capable of producing interference. The interference induced afforded protection not only against challenge with virulent staphylococci, but also against Diplococcus pneumoniae, Salmonella typhimurium, Escherichia coli, Proteus mirabilis, and one strain of influenza virus (A(2)J 305). Prior allantoic infection with avirulent staphylococci also protected against intravenous as well as allantoic infection with challenge strains.Interference required infection with viable bacteria. The onset of interference appeared within a few minutes after injection of the interfering strain, but was not maximal until 24 hours had elapsed between injection of the interfering and challenge strains. The protection afforded by the production of interference could not be overcome by increased inoculum size of the challenge strain and extended even to challenge with 10(9) bacteria. Studies of in vitro and in vivo growth of challenge strains in allantoic fluid demonstrated that some interfering strains inhibited growth of the challenge strains. Other strains produced interference without producing prolonged inhibition of the growth of challenge strains. Similarly, interference could not be attributed to attenuated virulence of the challenge organisms. All interfering strains studied produced enhanced bactericidal activity of whole blood from the affected embryos, but whether this affected leukocyte activity, opsonization, or other host defense mechanisms has yet to be determined.

Nephrotoxicity associated with cephalothin administration.

Variable degrees of acute renal failure developed in three patients receiving therapy with cephalothin sodium. The course and findings were consistent with acute tubular necrosis of the oliguric and nonoliguric types. One patient had protracted oliguria, a second experienced transient oliguria, and one had normal urine output. All had urinary sediment changes consistent with tubular necrosis, and the two oliguric patients had elevated urine sodium concentrations. No other causes for renal failure could be detected, and all recovered after discontinuation of cephalothin therapy, although peritoneal dialysis was required in one patient. These observations indicate that cephalothin is capable of inducing renal damage in man.

Nosocomial infection and fatality in medical and surgical intensive care unit patients.

We prospectively studied 526 patients admitted to the medical intensive care unit (MICU) and 799 patients admitted to the surgical intensive care unit (SICU) at a municipal hospital over a 20-month period. Rates of nosocomial infection were higher in the SICU patients (31% vs 24%). The SICU patients had more urinary tract infections, bacteremias, and wound infections, and the MICU patients were older, had higher acute physiology scores on admission and were more often admitted with shock or coma. The SICU patients were more likely to have received prior antibiotic therapy and had significantly higher numbers of endotracheal tubes, arterial lines, central venous lines, and indwelling bladder catheters. Of the 23 variables univariately associated with nosocomial infection, only five remained significant after entry into step-wise regression models. The MICU patients had a higher fatality rate in the MICU than did the SICU patients (18% vs 10%), but the relative risk of a death following nosocomial infection was 3.5 for both groups. Thirty variables were significantly associated with hospital fatality; nine remained significant after analysis by stepwise logistic regression.

Extrapulmonary tuberculosis revisited: a review of experience at Boston City and other hospitals.

During a 10-year period, 136 patients with extrapulmonary tuberculosis were seen at Boston City Hospital and other hospitals affiliated with Boston University School of Medicine. Review of these cases revealed that the prevalence of extrapulmonary tuberculosis was declining less rapidly than that of pulmonary disease. Extrapulmonary disease represented 4.5% of all new cases of active tuberculosis and tended to occur in older patients than in previous reports. Sites of involvement included lymph nodes, blood, genitourinary tract, bone and articular sites, the meninges, peritoneum, adrenal glands, pericardium, and miscellaneous sites, in this order. Diagnosis was confirmed by a variety of techniques whose relative merits are discussed. Overall, 14 deaths occurred among the 136 patients. One-half of the deaths resulted from causes other than tuberculosis and two patients died before diagnosis and initiation of therapy. Evaluation of the relative efficacy of therapeutic regimens was hampered by a high degree of recidivism in this population and the multitude of regimens utilized. These observations indicate that extrapulmonary tuberculosis still occurs with substantial frequency among patients seen in "inner-city" hospitals and that its recognition may be complicated by its occurrence in older patients with other medical conditions.

Bacteremia due to Mycobacterium tuberculosis in patients with human immunodeficiency virus infection. A report of 9 cases and a review of the literature.

Mycobacterium tuberculosis bacteremia is being reported more frequently in patients with human immunodeficiency virus, type 1 (HIV-1) infection. We report 9 patients with bacteremia due to M. tuberculosis and HIV infection who were identified over a 36-month period. Of the 9 patients studied, 8 were male, 8 were black, 6 were born in Haiti, 3 were homeless, 2 were intravenous drug users, and 1 was homosexual. At the time of diagnosis, 3 patients had the acquired immunodeficiency syndrome (AIDS) and 5 patients had CD4 lymphocyte counts less than or equal to 170 cells/mm3, indicating marked immunodeficiency. All 9 patients presented with temperature greater than 38.3 degrees C, 5 (50%) had abnormal chest roentgenogram on admission, and each of the patients tested had elevations of at least 2 liver function tests. Eight patients (80%) had M. tuberculosis isolated from sputum or other body fluids and tissues. All blood isolates of M. tuberculosis were identified from Dupont Isolator tubes. Antibiotic-resistant isolates of M. tuberculosis were cultured from 3 of the 6 patients born in Haiti. One patient died before diagnosis and received no antimycobacterial therapy; 7 of the remaining 8 patients appeared to respond to treatment. Our data, and a review of the literature, suggest that bacteremia due to M. tuberculosis is becoming more frequent, and that blood cultures may be helpful in establishing or confirming a diagnosis of tuberculosis in patients with HIV-1 infection.

Meningitis caused by Acinetobacter calcoaceticus var anitratus. A specific hazard in neurosurgical patients.

Acinetobacter calcoaceticus var anitratus caused meningitis in five patients between 1968 and 1978 at two hospitals affiliated with Boston University School of Medicine. All patients had had head trauma or neurosurgical procedures prior to the development of meningitis. The course of the disease was relatively indolent in that fulminant disease did not occur even when initial therapy was inappropriate and bacteria persisted in CSF. All five patients survived. On Gram's stain of CSF, A calcoaceticus may be confused with meningococci, pneumococci, or Haemophilus influenzae and thus cause delay in appropriate diagnosis and therapy.

Bacteremia due to Fusobacterium species.

Twenty-six patients were identified as having bacteremia with Fusobacterium species over a five-year period at Boston City Hospital. They represented 0.9 percent of bacteremic patients and were equally divided as to sex. Bacteremia with Fusobacterium occurred primarily in young adults and in patients over 60 years of age and was not observed in children. In 16 patients (62 percent), Fusobacterium was the only blood culture isolate. The most common primary foci of infection were the female genital tract, the upper respiratory tract, the oral cavity, and the lower respiratory tract. Five patients had primary foci of infection that were initially occult. Three of these patients were found to have unappreciated oral and pharyngeal lesions, and one had a liver abscess; no primary infection was established in the remaining patient. Shock related to bacteremia developed in six patients (23 percent), four of whom had Fusobacterium species as the only blood culture isolate. Death occurred in three patients (12 percent), all of whom were over 60 years old. Metastatic infection occurred in only one patient in whom hematogenous osteomyelitis developed. Postpartum fusobacterial bacteremia was uniformly benign. Evaluation of bacteremia with Fusobacterium species in nonpostpartum patients, without an overt focus of infection, should be directed to a search for occult abscess, especially of the upper respiratory tract and oral cavity.

Pathophysiology of bacteremia.

Despite the frequency and importance of both nosocomial and "community-acquired" bacteremia, definitive information concerning crucial pathophysiologic events in human bacteremia remains sparse. An extensive variety of clinical manifestations, such as fever, rigors, shock, altered circulatory dynamics, cutaneous manifestations changes in the coagulation, complement, and other mediator systems, and effects on the lungs, heart, kidney, liver, and other end organs, have been described, but it is difficult to determine the relative frequency of these events in bacteremia caused by different species. The extensive number of bacterial species capable of producing bacteremia and variations in the type of presentation, such as acute, asymptomatic, and chronic, even when bacteremia is produced by the same species, undoubtedly contribute to this difficulty and suggest that a variety of pathophysiologic mechanisms occur in various bacteremias. In contrast, the relative frequency of various manifestations and some pathophysiologic mechanisms have been better delineated in Gram-negative bacteremia. The development of bacteremia enhances the lethality of most types of localized infection and several studies have demonstrated a relation between the magnitude of bacteremia and the outcome of the disease. Among various pathophysiologic alterations, mechanisms involved in the production of fever have been delineated most clearly. Fever appears to reflect a "common pathway" with almost all infectious agents and results from release of endogenous pyrogen from phagocytic cells. Endogenous pyrogen regulates the thermostatic setting of the body through its effect on the anterior hypothalamus. Endogenous pyrogen seems identical with Interleukin 1 and exerts a variety of other biologic activities. An extensive number of bacterial components have been proposed as "effectors" and an equally large number of endogenous substances proposed as "mediators" of the pathophysiologic events in bacteremia. The importance of many of these effectors and mediators has been postulated largely on the basis of in vitro and animal studies. The lack of critical clinical studies hampers extrapolation of these experimental studies to human bacteremia. The development of more effective therapy for the complications of bacteremia, such as shock, will continue to be hampered until the mechanisms involved in the production of those pathophysiologic events that are crucial determinants of outcome have been delineated more precisely in human disease.

Bacterial infections in adult patients with the acquired immune deficiency syndrome (AIDS) and AIDS-related complex.

Sixty-four episodes of bacterial infection were identified over a 44-month period in 16 of 28 patients with the acquired immune deficiency syndrome (AIDS) and 14 of 31 patients with AIDS-related complex. Nineteen of the 30 infected patients were parenteral drug abusers, 10 were from Caribbean Islands and had no identified risk factor, and one was a homosexual male. Fourteen patients had 21 episodes of community-acquired pneumonia: Streptococcus pneumoniae (10), Haemophilus influenzae (three), other Haemophilus species (three), group B beta-hemolytic streptococci (one), Staphylococcus aureus (one), Branhamella catarrhalis (one), Legionella pneumophila (one), and Mycoplasma pneumoniae (one). Seven patients had eight episodes of nosocomial pneumonia caused by gram-negative bacilli. Twenty-five episodes of community-acquired bacteremia and nine episodes of nosocomial bacteremia were associated with specific sites of infection. Other infections included meningitis (two), urinary tract infection (one), and abscesses involving subcutaneous and deep tissues (12). Sixteen patients had recurrent infections; 11 of these had or eventually had AIDS. Community-acquired bacterial infections in patients with AIDS or AIDS-related complex are common and may be recurrent but have low fatality rates. In comparison, nosocomial bacterial infections occur primarily in patients with AIDS and have high fatality rates.

Gram-negative bacteremia. IV. Re-evaluation of clinical features and treatment in 612 patients.

Clinical features and specific aspects of treatment were evaluated in 612 patients with gram-negative bacteremia observed over a 10 year period. Coagulation abnormalities or thrombocytopenia were observed in 64 per cent of the patients. Evidence of disseminated intravascular coagulation (DIC) was found in approximately 10 per cent of them but was of sufficient severity to be associated with subcutaneous or visceral bleeding in 3 per cent of them. The frequency of coagulation abnormalities, other than DIC, was greater in patients with more severe underlying disease but DIC occurred with similar frequency irrespective of the severity of underyling host disease. Coagulation abnormalities of all types were associated with increased fatality rates. Hypothermia was noted in 13 per cent of the patients at the onset of bacteremia but was transient and was not associated with increased fatality. Failure to mount a febrile response greater than 99.6 degrees F within the first 24 hours of bacteremia was associated with a significant increase in fatality rates. Prior corticosteroid therapy diminished the febrile response to bacteremia. Age, underlying host disease, granulocytopenia, congestive heart failure, diabetes mellitus, renal insufficiency, nosocomial infections, and antecedent treatment with antibiotics, corticosteroids, and antimetabolites significantly increased fatality rates. Appropriate antibiotic treatment reduced the fatality rate of those with bacteremia by approximately one-half among patients in each category of severity of underlying host disease. In addition, it was shown that early appropriate antibiotic therapy also reduced the frequency with which shock developed by one half. Even after development of shock, appropriate antibiotic therapy significantly reduced fatality rates. The use of combinations of antibiotics could not be demonstrated to significantly improve survival rates. Minimal differences in therapeutic efficacy could be demonstrated between individual antibiotics and various combinations of antimicrobials. Shock occurred in approximately 40 per cent of the patients and its frequency was not influenced by the species of etiologic agent. Contrary to previous reports, corticosteroid therapy in patients with shock did not enhance survival and treatment with an average of 4.0 g/day of hydrocortisone or its equivalents was associated with a significant increase in fatality rates.

Contaminated medication nebulizers in mechanical ventilator circuits. Source of bacterial aerosols.

The contamination rates of medication nebulizers inserted into mechanical ventilator circuits were studied. Semiquantitative techniques were used to sample the reservoir fluid from in-line nebulizers during the first 24 hours after a circuit change. In the initial survey, high levels of contamination (organism concentrations above 10(3)/ml) were present in 13 (68 percent) of the 19 nebulizer reservoirs, and bacterial aerosols were produced by 10 (71 percent) of 14 nebulizers. Gram-negative bacilli were the predominant organisms isolated. Nebulizer contamination originated primarily from reflux of contaminated condensate in the ventilator circuit. When nebulizers were cleaned after each treatment, a reduced rate of contamination was found. Small bacterial aerosols (less than 3 microns in size) were produced in vitro after inoculation of nebulizers with gram-negative bacilli in concentrations isolated from in-use nebulizers. Contaminated in-line medication nebulizers generate small-particle bacterial aerosols that may increase the risk of ventilator-associated pneumonia and therefore should be cleaned or disinfected after each treatment rather than every 24 hours.

Xanthogranulomatous pyelonephritis caused by methicillin-resistant Staphylococcus aureus.

Localized xanthogranulomatous pyelonephritis due to methicillin-resistant Staphylococcus aureus developed in a 41-year-old diabetic patient. She had recurrent bacteremia despite appropriate therapy with vancomycin. Nephrectomy was required for cure and clinical diagnosis. This report emphasizes differences in the clinical presentation and pathogenesis of xanthogranulomatous pyelonephritis caused by S. aureus. Compared with the common form of xanthogranulomatous pyelonephritis caused by gram-negative bacilli, the localized disease due to S. aureus probably results from hematogenous seeding and is not associated with nephrolithiasis or ureteral obstruction. Furthermore, this report indicates that xanthogranulomatous pyelonephritis may be caused by methicillin-resistant S. aureus, a rapidly emerging nosocomial pathogen.

Gram-negative bacteremia. III. Reassessment of etiology, epidemiology and ecology in 612 patients.

Evaluation of 612 episodes of gram-negative bacteremia over a 10-year period demonstrated its progressively increasing frequency. This increase was associated with an increasing proportion of patients with more severe underlying disease, increasing patient age, increasing frequency of cardiac surgery and manipulative procedures, and increasing frequency of treatment with antibiotics, corticosteroids and antimetabolites in patients with bacteremia. Fatality rates paralleled the severity of the host's underlying disease as noted in previous reports. The urinary tract was the most frequent source of bacteremia, but in 30 per cent of the patients, predominantly those with more severe underlying disease, the original source could not be identified. Of all blood cultures obtained in these patients, 72 per cent were positive. Bacteremia was of low magnitude with 77 per cent of the patients have quantitative blood cultures with less than 10 gram-negative bacilli per milliliter of blood. Escherichia coli was the most frequent etiologic agent followed in frequency by Klebsiella-Enterobacter-Serratia species, Pseudomonas aeruginosa, Proteus and Providencia species, and species of Bacteroides. Sixteen per cent of the bacteremias were polymicrobic. K and O-antigen typing of Escherichia coli and capsular typing of K. pneumoniae demonstrated that a large number of serologic types of these strains were responsible for bacteremia. Over-all, bacteremia caused by multiple species of bacteria was associated with higher fatality rates, but no significant differences in fatality rates could be demonstrated for bacteremias caused by individual species of gram-negative bacilli when comparisons were made between patients with underlying diseases of similar severity. The presence or type of K-antigen did not influence the lethality of Esch. coli infections. Although some O-antigen types, 0:4, 0:6 and 0:8, were associated with higher fatality rates than other O-antigen types, "rough" or autoagglutinable Esch. coli were as lethal as smooth strains. These findings indicate that bacterial factors, other than antibiotic resistance, have little influence on the outcome of gram-negative bacteremia and that gram-negative bacilli function primarily as "opportunistic" pathogens.

A large outbreak of infections caused by a strain of Staphylococcus aureus resistant of oxacillin and aminoglycosides.

An extensive outbreak of nosocomial infections caused by oxacillin- and aminoglycoside-resistant Staphylococcus aureus (OARSA) occurred over a 16 month period. A total of 349 isolates of OARSA were obtained from 174 patients. Colonization with OARSA was found in 92 patients. There was 120 infections in 82 patients; 50 were surgical wound infections, 13 were nonsurgical wound infections, six were pneumonias, 15 were urinary tract infections, 12 were intravenous site infections, and there were 19 episodes of bacteremia (seven transient, 12 persistent). In patients with persistent bacteremia, the mortality rate was 33 percent. In patients treated for persistent bacteremia with vancomycin, the survival rate was 80 percent. Infections were highly associated with the surgical intensive care unit, and 90 percent of the isolates of OARSA tested had the same phage-type. Elderly patients with significant underlying disease, a history of previous surgery or of prior antimicrobial therapy appeared to be at increased risk for OARSA infections. OARSA were resistant to multiple antibiotics besides oxacillin, but all isolates were sensitive to vancomycin and rifampin. Three surgical intensive care unit nurses were found to be nasal carriers of OARSA, and one nurse had dermatitis of both hands colonized with OARSA. Following the removal of these nurses from the surgical intensive care unit and the institution of strict infection control measures, the number of OARSA infections and colonizations decreased to less than one per month. OARSA produces serious nosocomial disease, and epidemiologic intervention was effective in controlling this outbreak.

Methicillin-resistant Staphylococcus aureus bacteremia linked to intravenous drug abusers using a "shooting gallery".

Over a 15-month period, seven intravenous drug abusers had 10 admissions because of bacteremia due to methicillin-resistant Staphylococcus aureus. Seven episodes of probable bacterial endocarditis occurred in four patients; one patient had septic thrombophlebitis and two had soft tissue infections. All seven patients patronized a local "shooting gallery" where paraphernalia were provided and drugs were often administered by a "street doctor." All isolates were phage type 29/77/83A/84/85 and demonstrated resistance only to methicillin, oxacillin, and penicillin. This strain of methicillin-resistant S. aureus has a phage type and antibiogram that is distinct from nosocomial methicillin-resistant S. aureus and was probably acquired by intravenous drug abusers during visits to the "shooting gallery". The "shooting gallery" is an integral part of the drug culture and a likely source for the transmission of antibiotic-resistant organisms.