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Indian Journal of Cancer
Medknow Publications on behalf of Indian Cancer Society
ISSN: 0019-509X EISSN: 1998-4774
Vol. 46, Num. 4, 2009, pp. 260-261

Indian Journal of Cancer, Vol. 46, No. 4, October-December, 2009, pp. 260-261

Guest Editorial

Empirical versus theoretical

Professor of Medical Oncology and Deputy Director, Research and Surgical Services, Gujarat Cancer and Research Institute, Ahmedabad-380 016
Correspondence Address:Professor of Medical Oncology and Deputy Director, Research and Surgical Services, Gujarat Cancer and Research Institute, Ahmedabad-380 016
shilinshukla@gmail.com

Code Number: cn09066

PMID: 19749454
DOI: 10.4103/0019-509X.55544

Empirical and theoretical are two words (adjectives) that have opposite dictionary meanings. The former connotes ′anything based on experiments′ and the latter means ′anything based on ideas and principles′. Neither of them means that the action is based on one′s belief. However, in practice, the word empiricism is often used to convey tendency to act on the basis of one′s own simple, untested, anecdotal experience or sometimes something based on one′s own ideas and beliefs. And hence, often it is condemned or looked down upon as less scientific if it tends to cover such practices as inappropriate use of antibiotics to treat fever rather than infection or excessive use of broad-spectrum antimicrobials in the absence of definite diagnosis of causative organism.

However, modern day empirical antimicrobial therapy is based on repeated review, testing and sound knowledge of possible microbes and antimicrobials available coupled with institutional ′sepsis protocol′ or ′antibiotic policy′ developed on the basis of regular microbial surveillance, culture and sensitivity testing and clinical antibiotic audit. Hence, empirical antibiotic therapy has both experimental and theoretical components. The experimental components are locally evaluated institutional experience and shared global and experimented experience. The theoretical background is provided by sound knowledge of microbes, their pathogenicity and susceptibility, host response patterns, immunological factors, pharmacodynamics and pharmacokinetics of antibiotics.

In that light, the original article published in this issue, ′Comparison of in vitro activities of ceftazidime, piperacillin-tazobactam and cefoperazone-sulbactam, and the implication on empirical therapy in patients with cancer′ by Prabhash et al . [1] of the Tata Memorial Hospital is a welcome exercise of generating institutional experience to guide policy on empirical use of antimicrobials. Such Indian experiences are valid and applicable, in a limited sense, elsewhere also.

Empirical antibiotic in patients with cancer is often warranted because of the urgency in starting bactericidal therapy, as often the picture is complicated by the presence of prolonged neutropenia, immune-suppression and/or mucosal breach that may endanger life or make it miserable. Generally, it is started as soon as the clinician is convinced that symptoms of the patients are due to some infection (site and type may or may not be defined clearly) and necessary samples are taken for identification, culture and sensitivity testing.

One has to realize that any fever, aches, cough, diarrhea etc. may be due to noninfective processes also. In a neutropenic and immunosuppressed patient, except for pain and fever, all signs of infection are either subdued or absent. Fever without chills or rigors may suggest noninfective processes like cancer, drug fever, etc. Pneumonia may be associated with minimal or no respiratory complaints but routine x-ray chest may reveal the real threat to life and urgency of action necessitating use of empirical antibiotic therapy. Often time available is short. Therefore, antibiotic which is most effective and most likely to be successful is preferred. Generally, bacteria invade first but sometimes virus and fungus may be the primary or prominent causative agents, especially in haematological malignancy and in immune-suppressive states (e.g. bone marrow transplantation). Thus the situation is often complicated by both atypicality of organisms and atypicality of manifestations.

In a well-controlled haematological malignancy, neutropenic fever may herald, or may be the first manifestation of relapse. As against that, a nonneutropenic fever in a haematological malignancy may not, always, be a major cause for concern and may not warrant use of higher broad spectrum empirical antibiotic therapy if the infection is nonvisceral. Community acquired infections are usually due to Staphylococcus aureus and very rarely pseudomonal. However, in a neutropenic or immunosuppressed patient, an intrinsic source like gastrointestinal tract or urinary tract may lead to gram-negative septicaemia that warrants urgent and energetic intervention.

The site of infection may suggest possible causative agents in neutropenic patients also. Pharyngeal ulcers may harbour Pseudomonas aerugenosa or Herpes simplex , esophagitis may be caused by Candida spp. or H. simplex and painful defaecation may suggest perianal infection with Pseudomonas aerugenosa or other gram negative organisms. Sometimes symptoms of typhlitis and pseudomembranous colitis may help in selecting empirical antibiotic. Skin lesions of ecthyma gangrenosum may suggest infection with Pseudomonas aerugenosa . Gram negative enteric bacilli, S. aureus , aspergillus or mucor may cause destructive lesions in the lung. Venous access site infections are often S. aureus including multidrug resistant S. aureus (MRSA). If one develops sinusitis or visceral involvement following broad spectrum antibiotic therapy, it may be due to Aspergillus , Candida spp. or atypical organisms like Trichosporon beigelii , Fusarium species, Geotrichum candidum , Pseudallescheria boydii etc. [2]

Generally, when causative organism is not identified and empirical antibiotic therapy is continued, fever subsides when infection is under control and neutropenia has recovered. If fever reappears, one should rule out hepatic fungal infection (as part of systemic fungal infection) that usually raises serum alkaline phosphatase.

In a substantial number of cases, causative organism or focus of infection is not identified and hence empirical antibiotic therapy based on international guidelines, local surveillance, culture-sensitivity data and clinical antibiotic audit (after collecting samples for identification and susceptibility pattern of causative agents) is started and continued till lack of response or availability of culture and sensitivity report. Frequent and prolonged use of broad spectrum antibiotics changes microorganismal environment and repeated reviews, retesting, surveillance and audit become important part of our efforts to formulate and revise institutional guidelines. Sharing such information with colleagues elsewhere is also enormously useful. Therefore, one may only agree with such a need expressed by the authors of the above mentioned original paper. Ceftazidime is increasingly losing ground to piperacillin-tazobactam and cefoperazone-sulbactam. Rising incidence of resistance to these fixed drug combinations is of major concern. However, use of a carbopenam as upfront monotherapy possibly might require a few more studies for its support. Its failure may lead one to a situation of diminishing returns.

References

1.Prabhash K, Medhekar A, Biswas S, Kurkure P, Nair R, Kelkar R. Comparison of in vitro activities of ceftazidime, piperacillin-tazobactam, and cefoperazone-sulbactam, and the implication on empirical therapy in patients with cancer. Indian J Cancer 2009;46:318-22.  Back to cited text no. 1  [PUBMED]  Medknow Journal
2.Gantz NM, Brown RB, Berk SL, Myers JW. Manual of clinical problems in infectious disease. 5th ed. Indian: Lippincott Williams and Wilkins; 2006. p. 279-82 and 319-24.  Back to cited text no. 2    

Copyright 2009 - Indian Journal of Cancer

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