Aminoglycosides often are employed for empiric therapy of nosocomial infection because of their activity against a wide spectrum of gram-negative aerobic bacilli (GNAB). New beta-lactam antimicrobials also are active against many GNAB. As toxicity appears less likely for the beta-lactams than for aminoglycosides, their use might be preferable if susceptibility profiles were equivalent.

We studied susceptibility of 90 GNAB recovered from blood culture during a three-month period. All were susceptible to aminoglycosides; 93% were susceptible to at least one of the following: ampicillin, carbenicillin, ticarcillin, cephalothin, chloramphenicol or trimethoprim-sulfamethoxazole. All were susceptible to at least one of our newer beta-lactams (cefamandole, cefoxitin, cefotaxime, moxalactam, piperacillin), but the percentage susceptible to any single beta-lactam was lower than that for any of the aminoglycosides tested. All of the isolates were susceptible to combinations of two beta-lactam drugs.

In our hospital, beta-lactams may be reasonable alternatives to aminoglycosides in selected cases where susceptibility has been demonstrated. However, aminoglycosides continue to provide the broadest single-drug coverage for empiric therapy of known or suspected sepsis with GNAB. The utility of combinations of beta-lactam drugs for empiric therapy requires further assessment by clinical trials.

A nursery outbreak of diarrheal illness caused by Salmonella nienstedten initially involved seven infants cared for in one nursery; secondary infection subsequently affected one infant cared for in the same nursery as well as four other infants. Recognition of the outbreak was delayed due to an unusually long incubation period. The period from last known exposure to onset of diarrhea ranged from two to 18 days, with a median of ten days. The prolonged incubation period may have resulted from a low inoculum of the organism, from a previously unknown characteristic of Salmonella nienstedten, or may be an age-specific response. Hospital infection control personnel should be aware that nosocomial cases of salmonellosis may have a longer incubation period than has been previously recognized.

Patients requiring intensive care are usually at higher risk than other patients of becoming colonized or infected with organisms of special clinical or epidemiologic significance. Three reasons are that contacts between these patients and personnel are frequent, the patients are clustered in a confined area, and many of them are unusually susceptible to infection. Moreover, critically ill patients are more likely to have multiple invasive procedures performed on them. Because there is ample opportunity for cross-infection in the Intensive Care Unit (ICU), infection control precautions must be done scrupulously. Frequent in-service training and close supervision to ensure adequate application of infection control and isolation precautions are particularly important for ICU personnel. (See Guideline for Hospital Environmental Control: Intensive Care Units.)

Most ICUs pose special problems for applying isolation precautions, hence some modifications that will neither compromise patient care nor increase the risk of infection to other patients or personnel may be necessary. The isolation precaution that will most often have to be modified is the use of a private room. Ideally, private rooms should be available in ICUs, but some ICUs do not have them or do not use them for patients who are critically ill if frequent and easy accessibility by personnel is crucial. When a private room is not available or is not desirable because of the patient's critical condition, and if airborne transmission is not likely, an isolation area can be defined within the ICU by curtains, partitions, or an area marked off on the floor with tape. Instructional cards can be posted to inform personnel and visitors about the isolation precautions in use.

The dissemination of resistance determinants among bacterial populations depends on ecological and epidemiological properties as well as additional factors: 1) the mechanism of resistance or its specificity toward a certain drug, and 2) the genetic basis in relation to the mobility of the genetic material and its survival in bacteria. From two resistance mechanisms directed toward old-fashioned drugs, namely sulfonamides (Su) and streptomycin (Sin), we can deduce that a resistance mechanism is encoded by a special sort of genetic material. Thus the linked SmSu resistance mediated by a sulfonamide-resistant dihydropteroatsynthetase II and the aminoglycoside phosphotransferase APH-(3") is always located on very small pBPl-like plasmids. Such plasmids survive without selective pressure of drugs in Enterobacteriaceae in the bowel flora of humans and animals. Both resistance determinants can be mediated by a transposon which codes for the production of a dihydropteroatsynthetase I in connection with an aminoglycoside adenylyltransferase AAD-(3"). These two mechanisms are genetically linked as well. The basic structure is a transposon designated Tn2411, which belongs to a whole family of transposons, all including the basic structure; however, their genetic exchange and substitution leads to structures coding for many different enzymatic characters: ANT-(2") (Gentamicin resistance), CAT (Chlo-ramphenicol resistance), AAC-(6') (resistance to all modern aminoglycosides), TEM-1, OXA-1, OXA-2, or PSE (β-lactam resistance). Resistance to the modern (β-lactamase-stable antibiotics is mediated by mutation in the regulatory genes of chromosomally-determined (β-lactamases. A spread of these resistance mechanisms can be avoided as long as the responsible genes are not located on sufficient structures like small plasmids or efficient transposons.

The genetic determinants of antibiotic resistance originate as a result of random events, affected only by those physical and chemical agents that stimulate mutation. It is the selection and spread, within and between species, of new genetic material that is influenced by environmental factors, though the intrinsic antibiotic resistance of many opportunistic pathogens remains to be explained.

Depending on the frequency of genetic change, the biochemical resistance mechanism, the efficiency of selection (including access of antibiotic to relevant bacteria), and the opportunity for person-to-person spread, resistance may present in a number of ways. The use of an antibiotic in any individual may give rise to resistance, among pathogens or normal flora, to that antibiotic alone, to some or all members of its class, or to additional unrelated antibacterials, or to the acquisition of new bacteria, from a variety of sources (humans, animals, inanimate environment). A resistant organism may occasionally have other advantages that enable it to spread in the absence of the initial selective agents.

In the absence of controlled experiments, which are difficult or perhaps impossible, the only evidence of the truth of these hypotheses comes from the clinical use of antibiotics. A wise observer will conclude that the emergence of resistance is a rare event in an individual patient, but is commoner but by no means universal in populations, especially those that are closed. He will note the reports of diminished resistance in the presence of increased usage.

The role of academic infection control is to explain all the phenomena observed, and to formulate methods for identifying and countering the actual as opposed to the imagined hazards.

We performed a prospective study of infections following bone marrow transplantation in 50 patients treated for aplastic anemia or hematologic malignancy. Early, continuous prophylaxis with trimethoprim/sulfamethoxazole and oral nystatin, and empiric intravenous antimicrobial therapy during febrile granulocytopenic episodes were standard treatment for all patients. The use of trimethoprim/sulfamethoxazole did not appear to adversely affect donor marrow engraftment. Serious gram-negative bacillary and systemic Candida infections were uncommon. Although gram-positive bacterial infections were frequent, they were rarely associated with mortality. Aspergillosis emerged as the single most important infection, contributing to the death of nine patients. Cytomegalovirus diseases developed in 13 patients, seven of whom died. Patient age and chronic myelogenous leukemia were risk factors for the development of fatal infections. This study demonstrates that although certain serious infections can be controlled, there is a critical need for effective measures to prevent and treat aspergillosis and cytomegalovirus disease in these seriously compromised hosts.

Isolation precautions for newborns and infants may have to be modified from those recommended for adults because 1) usually only a small number of private rooms are available for newborns and infants, and 2) during outbreaks, it is frequently necessary to establish cohorts of newborns and infants. Moreover, a newborn may need to be placed on isolation precautions at delivery because its mother has an infection.

It has often been recommended that infected newborns or those suspected of being infected (regardless of the pathogen and clinical manifestations) should be put in a private room. This recommendation was based on the assumptions that a geographically isolated room was necessary to protect uninfected newborns and that infected newborns would receive closer scrutiny and better care in such a room. Neither of these assumptions is completely correct.

Separate isolation rooms are seldom indicated for newborns with many kinds of infection if the following conditions are met: 1) an adequate number of nursing and medical personnel are on duty and have sufficient time for appropriate handwashing, 2) sufficient space is available for a 4- to 6-foot aisle or area between newborn stations, 3) an adequate number of sinks for handwashing are available in each nursery room or area, and 4) continuing instruction is given to personnel about the mode of transmission of infections. When these criteria are not met, a separate room with handwashing facilities may be indicated.

This study evaluates the effect of a specially designed, physician-oriented handbook of antimicrobial use on the prescribing patterns of a group of 50 doctors at a university hospital. Data were evaluated over a period of one-and-one-half years, before and after the distribution of the handbook. For the purposes of this study, antimicrobial therapy was classified: 1) inappropriate if it violated one of a number of recognized principles of antimicrobial therapy, 2) appropriate if it agreed with specific recommendations or alternatives given in the distributed reference handbook, and 3) acceptable if it was neither inappropriate nor appropriate as defined by the handbook. An initial survey of antimicrobial prescribing patterns was made. Five months later the handbook was distributed. A two-week orientation program, consisting of the distribution and promotion of the problem-oriented, pocket-sized handbook of appropriate antimicrobial therapy, was conducted. The handbook, which was developed by the authors and reviewed and approved by a panel of infectious disease specialists, presented guidelines for appropriate and efficacious usage of antimicrobial agents as most currently accepted in common clinical infections. Subsequent surveys were then conducted two weeks, three months, and six months after distribution of the handbook. A statistically significant difference (p <0.01) in antimicrobial prescribing patterns was noted between the survey conducted two weeks after the introduction of the handbook and the other surveys. In this survey, while therapy classified inappropriate decreased from 45% to 28%, therapy considered appropriate as recommended increased from 33% to 53%. The findings of this study demonstrated that the introduction and promotion of the handbook decreased abuse and increased proper use of antimicrobial therapy, although the effect is sustainable for only a short duration—no longer than three months. These results indicate the need for a vigorous, updated program to achieve and maintain current appropriate antibiotic therapy in clinical medicine.

Much has been written recently concerning the new and growing occurrence of infections in compromised hosts. During the almost four decades since the end of World War II scientific investigation has produced extraordinary advances in diagnosis and treatment. This has resulted in two changes which have implications for this discussion. First, the classical acute community-acquired infections now are recognized quickly and treated effectively with antibiotics. Indeed, many such infections are managed quite effectively by physicians in the office or clinic and no longer require admission to the hospital. (For example, it has been years since I have seen mastoiditis or streptococcal erysipelas in my hospital consulting practice.) We have abandoned our “pneumonia ward” which once housed patients in various stages of life-threatening pneumococcal infection. Similarly, intensive immunization of our population has virtually eliminated poliomyelitis, diphtheria, tetanus, and measles; once common, these classical infectious diseases now are absent from our hospital.

The second effect of medical progress has been the opportunity to offer patients with certain diseases, previously untreatable, the hope of increased survival and even cure. The list here is long and includes premature infants, children with congenital immune deficiency disorders, individuals with leukemia, lymphoma, aplastic anemia, burns, renal and other organ failure, and many others. Thus, the numbers of such patients in our hospitals have increased. These patients are at an increased risk of acquiring a complicating infection because of their underlying disease or because of our diagnostic and therapeutic interventions.

Although the elderly are thought to be at increased risk for acquiring nosocomial infections (NIs), the degree of risk has not been carefully quantified. We determined the decade-specific risks of NIs. The rate was constant at approximately 10 per 1,000 discharged patients from birth to 40 to 49 years. Thereafter the rate rose logarithmically and peaked at greater than 100 per 1,000 discharges after 70 years. Of all NIs, 64% occurred after 60 years of age. Yet, this elderly group made up only 23% of hospitalized patients. In conclusion, while the elderly comprise a small fraction of hospitalized patients, they account for the majority of nosocomial infections.

Patients with certain diseases (for example, leukemia, cancer, and extensive skin conditions, such as severe burns or dermatitis) and patients who are receiving certain therapeutic regimens (for example, total body irradiation, steroid or antimetabolite therapy) are highly susceptible to infection. These compromised patients are often on special “protective” patient-care regimens intended to reduce the risk of infection. One such regimen, Protective Isolation (as outlined in the previous editions of Isolation Techniques for Use in Hospitals), does not appear to reduce this risk any more than strong emphasis on appropriate handwashing during patient care.

Protective isolation, as previously outlined, may fail to reduce the risk of infection because compromised patients are often infected by their own (endogenous) microorganisms or are colonized and infected by microorganisms transmitted by the inadequately washed hands of personnel or by nonsterile items used in routine protective isolation. Such items may include patient-care equipment, food, water, and air. Some studies suggest that vigorous efforts to exclude all microorganisms by using patient-isolator units, eradicating endogenous flora, and sterilizing food, water, and fomites may prevent or delay onset of some infections; thus, these procedures have been recommended by some for use with very-high-risk patients who have a predictable temporary period of high susceptibility. However, these extraordinary and expensive precautions do not appear warranted for most compromised patients.

In a prospective study of 372 patients undergoing cardiac surgery, we evaluated the relative contribution of host factors and patient care variables to the risk of postoperative wound infection. Host factors studied were age, sex, country of origin, the diagnosis for which the operation was performed and, for coronary artery by-pass operations, the functional cardiac status according to modified New York Heart Association criteria. The performance of more than one operation during a single admission carried the highest risk for infection, followed by a coronary artery by-pass operation lasting for more than six hours or performed on patients 65 years or older. In patients undergoing coronary artery by-pass surgery, host factors (age and cardiac function) were associated with infections in the chest wound, while the length of the operation was found to affect the occurrence of infections at the “donor” site.