Infectious Diseases

·         All patients with Candida fungemia should be treated with systemic antifungals. Fluconazole has been shown to be an effective agent for candidemia with equivalence to amphotericin products and caspofungin. For example, Candida glabrata is typically resistant to fluconazole. Voriconazole is also active against Candida albicans but has many drug interactions that make it less desirable against this pathogen. Azoles such as fluconazole and voriconazole are often less active against C. glabrata and C. krusei. Many practitioners therefore prefer to initiate treatment with caspofungin or amphotericin products in a patient with candidemia until the yeast isolate is definitively identified as C. albicans. Caspofungin and other echinocandins are gaining popularity due to their broad efficacy against most yeast isolates and benign side-effect profile. Amphotericin B is effective in fungemia but frequently causes rigors, electrolyte wasting, and renal insufficiency. Newer lipid formulations mitigate these effects to varying extents.

·         The differential diagnosis for nodular adenitis includes Sporothrix schenckii, Nocardia brasiliensis, Mycobacterium marinum, Leishmania braziliensis, and Francisella tularensis and is based on direct inoculation of organism due to contact from the soil, marine environment, insect bite, or animal bite.

·         HACEK endocarditis is typically subacute, and the risk of embolic phenomena to the bone, skin, kidneys, and vasculature is high. Vegetations are seen on ~85% of transthoracic echocardiograms. Cure rates are excellent with antibiotics alone; native valves require 4 weeks and prosthetic valves require 6 weeks of treatment. Ceftriaxone is the treatment of choice, with ampicillin/gentamicin as an alternative. Sensitivities may be delayed due to the organism’s slow growth.

·         Vibrio vulnificus is a ubiquitous, invasive, gram-negative rod found in warm, salty, coastal waters. It is found in zooplankton and shellfish and has been associated with two disease syndromes: (1) sepsis in alcoholics and persons with liver disease and (2) wound infections from minor abrasions and/or lacerations. Advanced cases can result in necrotizing vasculitis and gangrene.

It causes overwhelming sepsis in the immunocompromised host, particularly cirrhotic patients. Modes of infection are direct wound inoculation or ingestion via raw seafood. Presentation is rapid with the classic skin findings described in this case, which approximate purpura fulminans as the illness progresses. Mortality is >50%, even with appropriate and early antibiotics.

·         SID (selective intestinal decontamination), generally accomplished with fluorinated quinolones, suppresses gram-negative bacteria but not gram-positive bacteria. Therefore, patients on SID may have an increased frequency of gram-positive organisms as the etiology for SBP episodes.

·         HCV Dx: HCV RNA (PCR) > Anti-HCV (RIBA) > Anti-HCV (EIA)

·         The adherence of HAART necessary to secure durable viral control (95+%) is beyond many people's abilities.

·         Two types of resistance assays of HAART are available: genotypic resistance tests and phenotypic resistance tests. Genotypic tests are more readily available at this time. They involve sequencing HIV viral genes (i.e., reverse transcriptase, protease) and identifying mutations associated with drug resistance. Phenotypic tests assess the virus's ability to replicate in the presence of different concentrations of antiretroviral medications.

·         Clinically significant thrombocytopenia indistinguishable from that seen in idiopathic thrombocytopenic purpura (ITP) may be a presentation of HIV infection. Typically, bone marrow is normal with adequate numbers of megakaryocytes. The disorder behaves much like classic ITP in that patients respond to steroids and splenectomy. An HIV antibody test is recommended in patients presenting with ITP. Of interest is the recent recognition of thrombotic thrombocytopenic purpura in association with HIV infection.

·         Laboratory findings of PCP include hypoxemia with an elevated A-aO2 gradient. Elevated serum lactate dehydrogenase levels are seen.

Atovaquone is an alternative oral therapy for mild-to-moderate PCP (PO2 > 60 mmHg, A-a O2 gradient < 45 mmHg) in patients who cannot tolerate TMP-SMX. However, it is less effective than TMP-SMX, although equally as effective as pentamidine. The dosing regimen with the oral suspension is 750 mg twice daily, taken with a fatty meal, usually for 21 days. Because absorption depends on food intake, more acutely ill patients are not candidates.

·         Three drugs have been approved for prophylaxis against MAC: rifabutin, clarithromycin, and azithromycin.

·         Paradoxical reactions during TB treatment are defined as transient worsening or appearance of new signs, symptoms, or radiographic manifestations of TB that occur after initiation of treatment and are not the result of treatment failure or a second process. Such reactions were seen prior to the HIV epidemic and are still seen in HIV-negative TB cases, although they are rare. Paradoxical reactions have been reported in up to 35% of HIV/TB cases. Most reactions are also associated with the initiation of antiretroviral therapy, usually within days or weeks. They are most common in patients with advanced (CD4 < 50) AIDS. Common manifestations include: fever, new or increased adenopathy, new or worsening pulmonary infiltrates, and serositis, such as pleural effusions.

·         Immune reconstitution inflammatory syndrome IRIS: This syndrome is analogous to paradoxical reactions in TB treatment. In the setting of effective antiretroviral therapy, there is a rapid control of HIV viral replication and subsequent improvements in CD4 cell count and function. This immune reconstitution may then lead to inflammatory responses to clinically known or subclinical opportunistic infections. Most commonly seen is lymphadenitis due to MAC, the paradoxical reactions in TB, and exacerbations of cryptococcal meningitis and CMV retinitis. The more severe reactions, such as meningitis and retinitis, may result in administration of steroidal therapy.

·         Besides KS and non-Hodgkin's lymphoma, An additional AIDS-defining malignancy is invasive cervical cancer. Although not specific to HIV infection, it appears the clinical course is more aggressive in advanced HIV infection. All HIV-infected women need to receive routine screening for cervical cancer. Human papillomavirus (HPV) is involved in practically all cases of cervical cancer. Other non-AIDS-defining malignancies seen more frequently in HIV infection include Hodgkin's disease, anal cancer (also associated with HPV), lung cancer, and testicular cancer.

·         Many patients with HIV experience a distal sensory polyneuropathy. This may be due to HIV itself or treatment of HIV with certain neurotoxic nucleoside analogs, most commonly zalcitabine, didanosine, and stavudine.

·         Progressive multifocal leukoencephalopathy (PML) is a CNS demyelinating disease resulting from infection with JC virus.

·         Pneumococci do not produce plasmid-mediated penicillinase, but they can develop chromosomal mutations that confer resistance to penicillin by altering the affinity of the penicillin-binding proteins in their cell walls.

The pneumococcal polysaccharide capsule is crucial to virulence. The capsule allows the bacteria to resist phagocytosis by leukocytes. Although the polysaccharide capsule is the critical factor in determining the virulence of the pneumococci, several proteins, including surface protein A, contribute to the pathogenesis of pneumococcal infections.

In patients with pneumococcal pneumonia, a bronchopneumonic pattern is radiographically more common than lobar consolidation.

Cigarette smoking is the strongest independent risk factor for invasive pneumococcal disease in immunocompetent adults who are not elderly.

·         Patients with community-acquired bacteremias are more likely to have endocarditis and secondary metastatic infections than patients with nosocomial infections, who are more likely to have an evident portal of entry and severe underlying diseases.

·         Vancomycin is less effective than nafcillin for MRSA sensitive to both agents. Daptomycin and linezolid have excellent activity against van-comycin-intermediate and vancomycin-resistant Staphylococcus.

·         Teichoic acid is a carbohydrate antigen in the cell wall of staphylococci. Antibodies to teichoic acid can be detected in normal human serum. Teichoic acid has no established role in virulence, and antibodies to this antigen are not protective.

·         There is a strong association between S. bovis and carcinoma of the colon, and any patient with documented S. bovis bacteremia should be evaluated specifically for the possibility of colon carcinoma.

·         About 90% of patients with primary tuberculosis infection are asymptomatic. Thus, pleuritis is fairly uncommon, as are the three other potential manifestations of symptomatic primary infection (atypical pneumonia, extrapulmonary tuberculosis, and direct progression to upper lobe disease). Patients who are HIV positive, who are immunologically suppressed, or who are in some way debilitated are at increased risk for symptomatic primary infection.

Different atypical mycobacteria are sensitive to different antibiotics. For example, M. kansasii responds well to regimens containing rifampin, ethambutol, and isoniazid, and M. avium intracellulare complex (MAC) is most sensitive to the macrolides azithromycin and clarithromycin.

·         Rifampin is contraindicated in patients receiving protease inhibitors (PIs). It is also contraindicated in patients taking nonnucleoside reverse transcriptase inhibitors (NNRTIs) such as nevirapine, delavirdine, and efavirenz. Rifampin is a potent inductor of the cytochrome P-450 enzyme system, and reduced levels of both the PIs and NNRTIs can result from coadministration. Conversely, PIs can raise rifampin concentrations to potentially toxic levels.

·         Prophylaxis is recommended for close contacts of N.meningitidis persons. Close contacts are defined as household members, day care center contacts, and anyone directly exposed to the patient's oral secretions (as might occur through kissing, via mouth-to-mouth resuscitation, during endotracheal intubation, or during endotracheal tube management by health care workers not wearing appropriate masks). The likelihood of contracting invasive disease from close contacts is highest in the first few days after exposure.

·          A typical finding of clstridial myonecrosis is the absence of a prominent inflammatory response.

·         Metronidazole is the drug of choice for B. fragilis brain abscess because of its excellent penetration into the central nervous system and its virtually universal activity against Bacteroides species.

·         Antibiotics are the mainstay of therapy for Actinomyces infections, and penicillin is the drug of choice. Daily doses of Penicillin G 10 to 20 million units are usually administered intravenously for a period of 2 to 4 weeks, followed by oral therapy for 3 to 6 months.

·         It has repeatedly been demonstrated that single-dose penicillin therapy for early symptomatic syphilis is more likely to fail in an HIV-infected patient than in a patient with syphilis alone. HIV-infected patients have higher rates of false positive nontreponemal serologic test results.

·         Recent studies have suggested that treatment with antibiotics and antimotility agents is actually associated with an increased risk of developing HUS, especially in children. Thus, it is important to identify serotype O157:H7 in patients with the appropriate clinical picture; careful monitoring and supportive care is warranted in these patients. If requested, identification of the causative organism can be accomplished in most laboratories because this serotype ferments sorbitol slowly (unlike most other E. coli strains), allowing its identification on specific indicator plates.

·         V. vulnificus can cause overwhelming sepsis in compromised individuals. Patients particularly at risk are those with chronic liver disease or iron-overload states. Hemorrhagic bullous skin lesions are characteristic. Patients need not have diarrhea that would be expected with V. cholerae. Another clinical syndrome associated with V. vulnificus is that of local wound infection that progresses to fasciitis.For treatment, the drug of choice is tetracycline, with or without cefotaxime. With bacteremia, the mortality is over 50% despite appropriate antibiotic therapy.

·         Fever and abdominal pain are characteristically absent in patients with V. cholerae infections.

·         IN PERTUSIS, A single elevated antibody titer should be interpreted in relation to age-matched, population-specific controls. Paired specimens have limited utility because a rapid amnestic response to infection usually precludes the detection of a significant rise in antibody concentrations between acute and convalescent sera.

·         Brucella is a slow-growing organism that can be recovered from blood or bone marrow aspirates; the laboratory that performs the tests should be informed that Brucella is suspected, in order that the laboratory may keep blood cultures for 21 days.

·         Bacillary angiomatosis is an infection with B. henselae that primarily involves the skin and lymph nodes; it is often seen in patients with AIDS whose CD4+ T cell count is less than 100 cells/µl. Cutaneous lesions are produced by areas of neovascular proliferation associated with the inflammatory response to the bacteria. Lesions appear in crops and can have a papular, verrucous, or pedunculated appearance. They are typically red to purple and are difficult to distinguish from Kapsosi sarcoma. Regional lymphadenopathy is common. Systemic disease involving the liver, spleen, and bone also occurs. Peliosis hepatis is a characteristic finding in the liver and appears as hypodense lesions on abdominal CT. Treatment with erythromycin or doxycycline usually results in rapid improvement; this treatment should be continued for 2 months. Relapses are frequent after discontinuance of therapy, and some patients need lifelong treatment with tetracycline or a macrolide for disease control.

·         The distinction between gonococcal and nongonococcal arthritis is clinically useful, because gonococcal infections tend to have a better prognosis than nongonococcal arthritis. Progressive joint damage is uncommon in gonococcal arthritis.

Also, crystal arthropathy and septic arthritis may coexist; thus, the presence of crystals does not rule out septic arthritis, and cultures should be obtained when there is a clinical suspicion of septic arthritis or when a regimen of intra-articular corticosteroid injections is planned.

·         The lumbar region is most frequently involved in pyogenic hematogenous osteomyelitis. Thoracic vertebrae are often infected in spinal tuberculosis (Pott disease). The cervical spine is often the site of infection in patients who abuse I.V. drugs. Vertebral osteomyelitis is almost always the result of hematogenous seeding.

·         The absence of rash in RMSF does not correspond to milder disease; a small percentage of patients with so-called spotless RMSF have fatal illness. Doxycycline is the preferred agent in all patients except pregnant women, for whom chloramphenicol remains the agent of choice.

·         Antihistamines are not indicated in Acute Bacterial Sinusitis, because they thicken secretions and impair drainage. Nasal decongestants, such as pseudoephedrine, are a mainstay of therapy

·         The following four clinical criteria have been proposed as suggestive of group A streptococcal pharyngitis: tonsillar exudates, tender anterior adenopathy, absence of cough, and history of fever.

·         A new approach for Uncomplicated Otitis Media that merits study is a delayed-therapy strategy, in which an antibiotic is prescribed when otitis media is diagnosed, but the parents of the child are encouraged to fill the prescription only if the child's condition has not improved after 72 hours. Clearly, antibiotics do have a role in management of this common condition.

·         Lemierre syndrome occurs most commonly in children and young adults and is characterized by septic thrombophlebitis of the internal jugular vein, septic pulmonary emboli, and anaerobic bacteremia. It is typically caused by Fusobacterium necrophorum. Lemierre syndrome starts as pharyngitis with invasion into the deep pharyngeal tissue; this allows drainage into the lateral pharyngeal space and subsequent thrombosis of the internal jugular vein. CT scanning of the neck can lead to a diagnosis of thrombosis (ultrasound can also be used); blood cultures are important in identifying the pathogen. Penicillin G, metronidazole, and clindamycin have been the mainstays of therapy, although since the 1970s, Fusobacterium species have been found to be positive for βlactamase, and some authors recommend using antibiotics that are β-lactamase-stable or antibiotic combinations that include β-lactamase inhibitors. Heparin therapy has not been conclusively shown to improve outcomes, and ligation and surgical resection of the internal jugular vein are rarely necessary with adequate antibiotic therapy.

·         Hyponatremia, although common in many pathologic lung conditions, is suggestive of Legionella infection.

·         Three variants of SBP are recognized on the basis of culture and neutrophil counts of the ascitic fluid. In a strict sense, SBP is defined by an ascitic fluid with a positive culture and a PMN count > 250 cells/mm3. CNNA has a negative culture and a neutrocytic ascites (PMN count > 500 cells/mm3). Bacterascites is characterized by a positive ascitic fluid culture in the absence of neutrocytic ascites (PMN count < 250 cells/mm3). SBP and CNNA are indistinguishable clinically and are managed identically with antibiotics. Bacterascites in the absence of symptoms is usually self-limited and can be managed by observation and repeat paracentesis in 48 hours.

·         In patients without ascites, the omentum is very much liable to contain intra-abdominal abscesses. For this reason, paracentesis is usually not helpful in making a diagnosis. Four-quadrant paracentesis is used in the setting of peritonitis secondary to diffuse bowel disease, trauma, or surgery.

·         Because of the increased incidence of maternal mortality and premature births, asymptomatic bacteriuria in pregnant women is actively sought and is as aggressively treated and followed as symptomatic infection.

·         Hantavirus : HCPS & HFRS

HFRS clinical disease can be divided into four phases: febrile, cardiopulmonary, diuretic, and convalescent.

The mortality from HCPS is about 50%; most deaths are caused by intractable hypotension and associated dysrhythmia.

The deer mouse, Peromyscus maniculatus, is the reservoir for the Sin Nombre virus that causes the hantavirus pulmonary syndrome.

·         Parvovirus B19 causes erythema infectiosum (fifth disease) in otherwise healthy persons, aplastic crises in persons with hemolytic disorders, chronic anemia in immunocompromised hosts, and fetal loss in pregnant women.

·         Human paravaccinia infections result from direct contact with natural animal reservoirs of these agents; humans are only incidental hosts. Paravaccinia is an infection that produces lesions on the teats and oral mucosa of calves and milk cows. When humans are infected by direct contact, so-called milker's nodules develop on the fingers or hands; these nodules are occasionally associated with lymphadenitis.

·         One manifestation of HTLV-I infection is adult T cell leukemia (ATL). Four clinical types have been described: acute, lymphomatous, chronic, and smoldering. The most common by far is acute ATL. Acute ATL is characterized by a short clinical prodrome with an average of 2 weeks between the onset of symptoms and diagnosis. The clinical picture is characterized by rapidly progressive skin lesions, pulmonary infiltrates, and diarrhea. Patients with acute ATL have abnormal circulating lymphocytes with little lymphadenopathy. Lymphomatous ATL, the second most common type, accounting for 20% of cases, presents as lymphadenopathy in the absence of abnormal circulating cells. Both acute ATL and lymphomatous ATL are associated with hypercalcemia, not hypocalcemia. The other major manifestation of HTLV-I infection is HAM. This is a slowly progressive thoracic myelopathy. At onset, symptoms include weakness or stiffness in one or both legs, back pain, and urinary incontinence. On examination, patients characteristically have hyperreflexia, ankle clonus, extensor plantar responses, and spastic paraparesis. Cognitive function is generally not impaired.

·         In patients with long-standing HIV, the CD4+ T cell count will become more predictive of disease progression than will viral load.

·         The antibiotic of choice for listerial meningitis is ampicillin (or trimethoprim-sulfamethoxazole for the penicillin-allergic patient). Vancomycin, the cephalosporins (e.g., ceftriaxone), and the carbapenems (e.g., imipenem or meropenem) do not adequately cover Listeria.

·         Appropriate malaria chemoprophylaxis is the most important preventive measure for travelers to malarial areas. In addition to advice about the avoidance of mosquitos and the use of repellants, most visitors to areas endemic for malaria should receive chemoprophylaxis, regardless of the duration of exposure. In most parts of the world where malaria is found, including Africa, chloroquine resistance is common. Pyrimethamine-sulfadoxine is no longer recommended for prophylaxis because of the associated risk of serious mucocutaneous reactions. Mefloquine is the preferred agent for malaria chemoprophylaxis in areas of the world where chloroquine-resistant malaria is present. Although mefloquine is generally well-tolerated in prophylactic doses, underlying cardiac conduction abnormalities and neuropsychiatric disorders or seizures are generally considered contraindications for mefloquine use. Thus, daily doxycycline taken from the start of the travel period until 4 weeks after departure from malarial areas would be the best choice for malaria chemoprophylaxis for such patient.

·         Disseminated gonococcal infection is the leading cause of bacterial arthritis in young adults. This disease often starts as an early tenosynovitis-dermatitis syndrome, which is often followed by a septic arthritis.

·         Dogs are responsible for 80% of animal bites; organisms include P. multocida, Eikenella corrodens, and Capnocytophaga canimorsus (formerly called DF-2). Aeromonas hydrophila is the organism seen in bite wounds from alligators and other aquatic animals. Rabies is an acute viral disease of the central nervous system and is transmitted by infected dogs, cats, skunks, foxes, raccoons, mongooses, wolves, and bats. Pseudomonas aeruginosa may cause a variety of skin lesions, such as “hot tub folliculitis” and ecthyma gangrenosum. Vibrio parahemolyticus is an organism found in undercooked shellfish; patients present with diarrhea.

·         Acanthamoeba castellanii is associated with contact lens usage.

·         CARDINAL FEATURES OF BOTULISM

1.       Symmetric descending paralysis (diplopia, dysarthria, dysphonia & dysphagia)

2.       Absence of fever

3.       Responsive patient

4.       Normal or slow heart rate

5.       Absence of sensory deficits

·         Outbreaks of lymphocutaneous infection due to Sporothrix schenckii have occurred in nursery and forestry workers who handle seedlings packed in sphagnum moss. Disease has also been associated with contaminated hay, timbers, and thorny bushes, such as roses.

·         Bartonella species’ Infections:

B. bacilliformis: veruga peruana

B. quintana: Oroya fever (Carrion's disease), trench fever, bacillary angiomatosis/visceral peliosis, fever/bacteremia, endocarditis

B. henselae: lymphadenopathy, fever/bacteremia, bacillary angiomatosis/visceral peliosis, cat-scratch disease, endocarditis

B. elizabethae: endocarditis

B. clarridgeiae: cat-stratch disease

B. vinsonii subsp. berkhoffi: endocarditis

B. vinsonii subsp. arupensis: fever

B. grahamii: neuroretinitis

·         "LADY WINDERMERE SYNDROME" DUE TO MYCOBACTERIUM AVIUM COMPLEX

1. Elderly white women
2. No significant underlying disease
3. Multifocal, nodular bronchiectasis involving middle lobes and lingula
4. Nonsmokers
5. Isolation of M. avium complex in low numbers from sputum specimens

·         Koch postulates, which were actually proposed by Henle, are used to establish a causal relation between a specific agent and a specific disease:

1. The agent must be present in every case of the disease.
2. The agent must be isolated from the diseased host and grown in pure culture.
3. The specific disease must be reproduced when a portion of the culture is inoculated into a healthy susceptible host.
4. The organism must be recovered again from the experimentally infected host.

·         A. hydrophila, which has the same freshwater habitat as the medicinal leech, Hirudo medicinalis, may complicate microvascular surgical infections where leeches are used because of their anticoagulant properties.

·         Dirofilaria immitis, the dog heartworm, usually presents as a solitary, noncalcified pulmonary nodule in humans. Because humans are an unsuitable host for this worm, larvae that mature in subcutaneous tissues after inoculation by infected mosquitoes enter veins and travel to the heart and act as emboli into the pulmonary arteries, resulting in infarcts.