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False negative results may occur in urine specimens that did not remain in the bladder a sufficient length of time for the bacteria to reduce a measurable quantity of nitrate to nitrite. Other reasons for false negative results include high specific gravity, ascorbic acid levels above 25mg/dL or low pH (<6). Less frequently, the cause may be due to a lack of sufficient nitrate in the diet (green vegetables) or further reduction of nitrite to nitrogen when large numbers of bacteria are present. In patients receiving antibiotics, the metabolism of the bacteria may be inhibited which would also produce a false negative reaction.

Most S. pneumoniae strains gain penicillin resistance by altering the penicillin-binding proteins in their cell wall.Penicillin molecules that cannot find a penicillin binding site cannot interfere with cell wall synthesis.Several different types of penicillin binding proteins may be involved, explaining the various levels of intermediate resistance that may be encountered with different strains of S. pneumoniae.Because different penicillin binding proteins may be involved, the level of penicillin resistance cannot be predicted by the oxacillin screening test.Infections caused by isolates of S. pneumoniae showing penicillin resistance in the intermediate range may be successfully treated by administering high doses of antibiotic.For this reason, the level of resistance with an accurate MIC test must be determined for all clinically significant isolates of S. pneumoniae.

Citron DM. Appelbaum PC.: How far should a clinical laboratory go in identifying anaerobic isolates, and who should pay? Clinical Infectious Diseases. 16 Suppl 4:S435-8, 1993Identification of anaerobic bacteria in specimens from sites of infection due to mixed organisms can be time-consuming and expensive. Laboratories should limit anaerobic workups by testing only those specimens that have been properly collected and transported to the laboratory.Use of selective and differential media for initial processing can provide rapid and relevant information to the clinician. Anaerobes isolated from normally sterile sites and sites of serious infection should always be completely identified. Group-or genus-level identifications may suffice in other instances.The Bacteroides fragilis group of organisms should always be identified because of their virulence and resistance to many antimicrobial agents.Some of the other organisms that warrant identification include Clostridium septicum (associated with gastrointestinal malignancy); Clostridium ramosum, Clostridium innocuum, and Clostridium clostridioforme (which are resistant to antibiotics); Clostridium perfringens (a cause of myonecrosis and gas gangrene,potentially serious infection); anaerobic cocci (which may be resistant to metronidazole and clindamycin); and fusobacteria (which may be virulent and resistant to clindamycin and penicillin).

Hershow RC. Khayr WF. Smith NL.: A comparison of clinical virulence of nosocomially acquired methicillin-resistant and methicillin-sensitive Staphylococcus aureus infections in a university hospital (University of Illinois at Chicago). Infection Control & Hospital Epidemiology. 13(10):587-93, 1992OBJECTIVES: To compare the clinical virulence of nosocomially acquired methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) infections in 1989.DESIGN: A retrospective comparison of host factors, in-hospital exposures, sites of infections, and outcomes of patients with nosocomial MRSA and MSSA infections. PARTICIPANTS: Forty-four adult patients with nosocomial S.aureus infections.RESULTS: The 22 MRSA-infected and 22 MSSA-infected persons were similar regarding mean age, gender, underlying diseases, and exposure to surgery. Before developing infection, MRSA-infected persons were more likely to have received antibiotics and to have stayed in the hospital > 2 weeks. Bacteremia was the most common presentation in the MRSA and MSSA groups (55% and 59%, respectively). Infectious complications and death were infrequent in both groups.CONCLUSIONS: MRSA and MSSA strains infect patients with similar demographic features and underlying diseases, but MRSA infections are significantly more common among patients with previous antibiotic therapy and a prolonged preinfection hospital stay. Clinical presentations and outcomes did not differ significantly between the 2 groups. Thus, similar to studies in the early 1980s, our findings do not suggest greater intrinsic virulence of MRSA.

In follow up to the previous question, the upper image again illustrates the colonies recovered from the blood culture bottle. The colonies are small, transluscent, gray-yellow, and surrounded by a wide zone of beta hemolysis.The size of the colonies compared to the zones of hemolysis suggests a group A streptococcus.The susceptibility to bacitracin (zone of inhibition around the "A" disk)(lower photograph) is virtually diagnostic of a group A streptococcus.The absence of a zone of inhibition around the SXT disk indicates resitance to sulfamethoxazole/ trimethoprim. SXT resistance is also shared by group B streptococci, which are, however, resistant to bacitracin.The resistance to SXT is used for the primary recovery of groups A and B streptococci from specimens with mixed culture. Their resistance allows them to selectively grow out from contaminating bacteria that are inhibited by this antibiotic.

Rouquette C. Berche P. The pathogenesis of infection by Listeria monocytogenes Microbiologia. 12:245-58, 1996 Listeria monocytogenes is a Gram-positive bacterium responsible for severe infections in human and a large variety of animal species. It is a facultative intracellular pathogen which invades macrophages and most tissue cells of infected hosts where it can proliferate. The molecular basis of this intracellular parasitism has been to a large extent elucidated. The virulence factors, including internalin, listeriolysin O, phospholipases and a bacterial surface protein, ActA, are encoded by chromosomal genes organized in operons. Following internalisation into host cells, the bacteria escape from the phagosomal compartment and enter the cytoplasm. They then spread from cell to cell by a process involving actin polymerisation. In infected hosts, the bacteria cross the intestinal wall at Peyer's patches to invade the mesenteric lymph nodes and the blood. The main target organ is the liver, where the bacteria multiply inside hepatocytes. Early recruitment of polymorphonuclear cells lead to hepatocyte lysis, and thereby bacterial release This causes prolonged septicaemia, particularly in immunocompromised hosts, thus exposing the placenta and brain to infection. The prognosis of listeriosis depends on the severity of meningoencephalitis, due to the elective location of foci of infection in the brain stem (rhombencephalitis). Despite bactericidal antibiotic therapy, the overall mortality is still high (25 to 30%).

A lack of Vitamin K can cause a loss of functionality in Vitamin K dependant coagulation factors, specifically, factors II, VII, IX and X. Most often associated with a diet lacking in Vitamin K, it may also present in situations of broad spectrum antibiotic use, where normal flora in the gut have been eliminated. As one might expect, treatment involves a diet rich in Vitamin K containing foods, and judicious use of broad spectrum antibiotics.

Four major classes of drugs are frequently monitored by TDM: Antibiotics Anticonvulsants Immunosuppressants Cardiac medicationsThere are other drugs that are monitored by TDM that are not included in any of the above classifications, but the majority of TDM testing is performed for drugs that are included in one of these four categories.

This phlebotomist violated hospital procedures in several ways that could adversely impact patient care: Cleaning the site only with alcohol, not iodine, could result in a false-positive contaminated blood culture. This might result in the patient receiving unnecessary intravenous antibiotics, and could prolong the patients hospital stay unnecessarily. Drawing both cultures at the same time lessens the chance of recovering a bloodstream organism.Drawing both cultures from the same site might result in both of them being contaminated, making it very difficult for the physician to distinguish contamination from a “real” bloodstream infection.Relevant topics:Blood cultures: introduction, Avoid skin contamination, Blood culture site preparation 1, Blood culture site preparation 2

A direct smear is made from a clinical specimen, not a culture. It can be used to:Guide the physician on initial choice of antibiotic, pending results of culture and sensitivity.Judge specimen quality.Contribute to selection of culture media, especially with mixed flora.Provide internal quality control when direct smear results are compared to culture results.

The culture smear is used to determine the staining characteristic and shape of the unknown organism since this data helps the microbiologist to decide on additional culture and identification methods. By correlating the Gram stain reaction, colony morphology and growth requirements, the microbiologist may be able to tentatively identify the organism, which the physician may use to modify treatment, until definitive culture and antibiotic susceptibility results become available.

A 14 year-old boy came to the physician's office with a sore throat that progressively worsened over a three day period. His posterior pharynx was swollen ,shiney and erythematous. The boy complained of pain on swallowing. His temperature was 98.5F. A rapid direct streptococcal antigen test was positive. However, his symptoms did not subside over the next two days while on antibiotic therapy. Anorexia and nausea were persistent and compounded by a frontal headache. Cervical lymph nodes became noticeably enlarged. The results of the CBC were: WBC 11.9/mm3 with 17% segmented neutrophils, 5% bands, 72%(60% atypical--see photograph)lymphocytes and 6%monocytes. All red cell findings were normal. A monospot test was positive. This is a case of group-A streptococcal infection superimposed on infectious mononucleosis. Symptoms subsided in 3 weeks following completion of the antibiotic therapy.