What host factors lead to the development of urinary tract infections (UTIs), and how are these factors different for men and women?

What organisms commonly cause lower UTIs?

What are the signs and symptoms of lower UTI, and how do these differ from those of pyelonephritis?

TMP-SMX remains the drug of choice for the empirically based treatment of uncomplicated UTIs. For sulfa-allergic patients, ampicillin, amoxicillin, a first-generation cephalosporin, or a quinolone is the appropriate alternative. Therapy may then be modified on the basis of the urine culture results and the sensitivities of the infecting organism. Enterococci are not susceptible to either TMP-SMX or
cephalosporins, which points out the utility of performing urine Gram’s staining when deciding on antibiotic therapy. The prevalence of ampicillin-resistant E. coli may be as high as 30% in some communities, and this needs to be considered when selecting an appropriate antibiotic. S. saprophyticus responds to ampicillin, TMP-SMX, and the quinolones. In the past, treatment of lower UTIs for 5 to 7 days was recommended. Short course therapy with agents that achieve high and sustained urinary concentrations (single dose with one or two double-strength TMP/SMX or 3 g of amoxicillin) will usually suffice for uncomplicated infections. Failures of short course therapy are indications that complicating factors requiring more extensive evaluation might be present. In general, single-dose therapy is contraindicated in patients with known anatomic or functional abnormalities, or with immunocompromising diseases such as diabetes mellitus. After single-dose therapy urine cultures should be performed 1 to 2 weeks later, to document the cure. In the event of treatment failure, a longer course of the appropriate antibiotic should be administered and an evaluation of potentially complicating factors should be undertaken.

Regardless of the pathogen and the choice of antibiotics, aggressive oral hydration is a reasonable recommendation in the management of an uncomplicated UTI. Although there is no evidence that hydration improves the results of appropriate antimicrobial therapy, it does dilute the bacteria and removes infected urine by frequent bladder emptying.

Some women find that switching to another method of birth control considerably reduces the frequency of recurrent bacterial UTIs. Thorough cleansing of the perineal area before sexual relations may decrease the incidence of postcoital UTI in those prone to UTI; however, most patients find this to be an impractical and not completely effective preventive measure.

Choosing another method of birth control may not be necessary for most women if they remember to drink a large glass of water before intercourse and void after intercourse; however, studies have shown that diaphragm usage is an independent risk factor for UTI. Regular antibiotic prophylaxis should be reserved for those patients with a history of multiple recurrent UTIs, or complicated UTI or upper tract infections, or for immunocompromised hosts. The disadvantages of ongoing prophylaxis include the development of drug-related side effects and colonization with multidrug-resistant organisms.

No. Although lower UTIs in women are associated with sexual activity, this is not a sexually transmitted disease. The infecting organisms are usually endogenous flora. Healthy men without predisposing factors such as urinary tract instrumentation or diabetes mellitus rarely get lower UTIs. Bacterial prostatitis does not put his sexual partner at risk for cystitis.

When bacteriuria is found in Gram’s-stained, uncentrifuged urine, this is a very specific finding for the diagnosis of UTI. The finding of microscopic bacteriuria corresponds to urine culture colony counts of 10⁵/mL in more than 90% of such
specimens. Distinguishing between gram-positive and gram-negative infections can be quite useful in making therapeutic decisions.

Alkaline urine may be caused by infection with Proteus species, which produce urease. The presence of nonalkaline urine in this patient makes infection with a urea-splitting organism unlikely.

The physical examination and diagnostic studies performed in an emergency room setting should be directed toward elucidating the nature of the patient’s chief complaint and history. A pelvic examination would be appropriate if the patient had reported symptoms of increased vaginal discharge, dyspareunia, or exposure to a known sexually transmitted disease in the partner. The indications for performing cultures for sexually transmitted pathogens are similar to those for a pelvic examination. Chlamydia, Ureaplasma, N. gonorrhoeae, or Mycoplasma infection should have been considered in this patient if no organisms were seen on the Gram’s-stained urine specimens, or if subsequent routine bacterial cultures grew no organisms.

Intravenous pyelography and a renal ultrasound examination should be reserved for when a complicated UTI or upper UTI such as pyelonephritis is suspected. A pregnancy test should be performed in any woman of childbearing age before prescribing an antibiotic that may be contraindicated in pregnancy.

Phenazopyridine hydrochloride is a urinary tract analgesic agent that exerts a topical analgesic effect on the mucosa of the urinary tract through an unknown mechanism of action. The side effects are minimal, and include the urine acquiring a red or orange color that may stain fabric. It is usually not necessary to prescribe more than a 2-day supply to patients with uncomplicated UTIs who are receiving appropriate antibiotic therapy. Opioid analgesics are relatively contraindicated in UTI because they may cause acute urinary retention.

Vaginal candidiasis commonly develops after antimicrobial therapy because antibiotics eliminate much of the normal vaginal flora and create an ideal environment for the overgrowth of Candida albicans. Hypersensitivity reactions may occur with any antibiotic; however, TMP-SMX may rarely also be associated with interstitial nephritis, aseptic meningitis, Stevens-Johnson syndrome, or erythema multiforme. A careful history to rule out known drug allergy is important.

The consequences of noncompliance with therapy include continuing symptoms, the induction of antibiotic-resistant strains of microorganisms, and, most important, ascending infection leading to acute pyelonephritis or even a perinephric abscess.

What are the principles of antiretroviral chemotherapy?

When should antiretroviral chemotherapy be started?

What are the most important human immunodeficiency virus HIV-1–associated opportunistic infections, and the treatments used in the HIV-1–infected individuals who live in developed countries?

You should recommend to her that she initiate antiretroviral therapy. Although her CD4 cell count is in a range that would prompt some practitioners to recommend deferring therapy, the presence of vaginal thrush is a clinical indicator of HIV-1 disease and places her at greater risk for an opportunistic infection than a woman with the same CD4 cell count and no symptoms. Therapy should not be initiated until a viral susceptibility test result has been obtained. In her case, it reveals that her virus is resistant to efavirenz, likely reflecting the acquisition of the drug-resistant virus from her husband. Because of this, you should recommend a regimen that uses a boosted protease inhibitor as the anchor drug such as tenofovir, emtricitabine, and r/lopinavir.

The general approach to antiretroviral chemotherapy in pregnancy should be the same as it is in a nonpregnant woman. Effective management of an infected
woman requires close collaboration among an internist or infectious disease specialist with experience using antiretroviral therapy, an obstetrician with experience dealing with HIV-1–infected mothers, and a pediatrician with HIV-1 expertise. The dual goals of therapy in this setting are to suppress viral replication to benefit the mother and to decrease the risk of transmission of HIV-1 to her baby. With her CD4 cell count and plasma HIV-1 RNA level, she is at risk for disease progression over the next several years and, as mentioned in the preceding text, most experts would recommend antiretroviral chemotherapy to her once she is through her first trimester of pregnancy. Although there is no evidence that tenofovir places fetuses at risk, there is more experience with zidovudine and lamivudine in pregnancy; so it would be preferable to use these agents instead of tenofovir and emtricitabine. Because her virus is not susceptible to efavirenz, it would not be used. Nonetheless, even if her virus were susceptible to the drug, it should not be used in pregnancy because of concerns about teratogenicity. Although d4T and ddI are used less frequently these days, they should be avoided whenever possible in pregnant women because of lactic acidosis, hepatic steatosis, and pancreatitis. Nevirapine has been associated with severe hepatitis, especially in women with CD4 cell count more than 250/mm³ and should be avoided in this patient for that reason. Therefore, she would best be treated with a protease inhibitor as the anchor drug in her regimen. Although nelfinavir is often used in pregnancy, concerns about its potency dampen the enthusiasm for it—even in this setting. R/lopinavir is a very reasonable choice, although there are data that suggest increased metabolism of lopinavir during pregnancy. Therefore, drug levels should be followed-up.

Before the advent of antiretroviral chemotherapy, the likelihood of transmitting HIV-1 from mother to child was in the range of 25%. Zidovudine monotherapy administered during the third trimester of pregnancy, coupled with intravenous zidovudine during delivery and 6 weeks of zidovudine for the infant, reduced the risk of perinatal transmission to 8%. More potent contemporary antiretroviral chemotherapeutic regimens have reduced this risk to below 1%. The goal of therapy in the mother should be to reduce plasma HIV-1 RNA levels to less than 20 copies/mL by delivery. The baby should also receive antiretroviral chemotherapy as part of the perinatal transmission prevention strategy. The neonate should not be breastfed, regardless of the mother’s plasma HIV-1 level, in view of the risk of transmission of HIV-1 by this route.

Her husband has been infected for more than 5 years and has maintained a low plasma HIV-1 RNA level and a near normal CD4 cell count. Although he is technically not a long-term nonprogressor because he has not been documented to be infected for more than 10 years, his plasma HIV-1 RNA level and CD4 cell count predict that his disease progression risk is very low. Most experts would not recommend antiretroviral chemotherapy to him at this point. Although antiretroviral chemotherapy is not indicated, he should undergo a full initial evaluation for HIV-1 including a PPD, an RPR, and T. gondii and cytomegalovirus serology and should be followed-up at 3- to 6-month intervals for evidence of a rising plasma HIV-1
RNA level and/or a falling CD4 cell count. He should also be vaccinated against pneumococcal disease. It would also be prudent to test his virus for resistance to antiretroviral drugs to guide selection of his regimen when he requires therapy. Even if his virus is found to be susceptible to efavirenz, it should not be relied upon in his case because it is presumed that his wife acquired her resistant virus from him and it is known that drug-resistant virus may be overgrown by wild type virus in the plasma. In these situations, the lifelong persistence of drug-resistant minor species variants leads to treatment failure if these agents are used.

What factors predispose to the development of cellulitis?

What are the signs and symptoms of cellulitis?

What organisms most frequently cause cellulitis?

Group A streptococci and S. aureus must always be considered as potential causes of cellulitis because they are the most common etiologic agents. In the event of animal bites or scratches, the oral flora of the animal may be an important source of infection as well. Pasteurella multocida is found in the oropharynx of 50% to 70% of healthy cats and 12% to 60% of healthy dogs. This gram-negative rod is frequently implicated in infections resulting from cat bites or scratches, and is found less often in wounds inflicted by dogs. Other important animal oral flora to consider in patients with bites and scratch wounds include aerobic and anaerobic streptococcal organisms, as well as gram-negative anaerobes such as Bacteroides species and Fusobacterium. Organisms found in soil, such as Clostridia species, may also be transmitted by scratches or bites.

The rapid tempo of this patient’s illness, with the development of an exquisitely painful cellulitis within 24 hours of a cat scratch, is characteristic of P. multocida infection, although such a rapid course may also be seen in the setting of streptococcal infections. It would be unusual, however, for a staphylococcal infection to progress this rapidly. Moreover, the discharge from a staphylococcal infection would more likely be purulent than serosanguineous. The finding of many gram-negative rods on the Gram’s-stained specimen of the wound discharge also suggests a P. multocida infection, or a gram-negative anaerobic infection. However, a few gram-positive cocci in chains were also found, making streptococcal infection a part of the differential diagnosis.

This patient has a serious hand infection, along with an impending systemic illness. Anyone with such a serious hand infection should be hospitalized and receive intravenous antibiotics to prevent advancing infection, as well as to avert the potentially devastating consequences of suboptimal therapy. Penicillin is the drug of choice for P. multocida infections, and would also be effective for the management of both streptococcal and anaerobic infections. Therefore, intravenous penicillin would be the best antibiotic in this case. For patients who are allergic to penicillin, tetracycline is the best alternative drug for the treatment of P. multocida infections. The patient should also be seen in consultation with a hand surgeon to be certain that surgical intervention for drainage or decompression is not required.

Overestimating the efficacy of antibiotics, and underestimating the critical roles played by debridement, drainage, wound elevation, and immobilization, are probably the most frequent mistakes made in the treatment of cellulitis. Drainage of a closed-space infection and removal of necrotic tissue are essential for curing any infection. Even when the appropriate antibiotics are administered, an infection can worsen if abscesses or necrotic tissue are not drained or removed. The reason for this is that abscesses and necrotic tissue are not well vascularized, making them inaccessible to both the antibiotics and the host immune mechanisms, such as polymorphonuclear leukocytes and complement, which are normally conveyed through the bloodstream. Therefore, in these inaccessible regions bacteria can freely multiply and, in some instances, such infection can result in sepsis and death despite an appropriate antibiotic regimen.

Abscesses tend to develop in the setting of P. multocida infection. In addition, the hand contains several physiologic spaces, such as the thenar eminence, that can serve as pockets of infection. Therefore, a P. multocida cellulitis of the hand may require surgical debridement and drainage. Incision of a hand wound should not be performed by a novice, because there is a great potential for damaging internal structures or creating wounds that would result in serious contractures. A hand surgeon should be consulted for this purpose.

The objective of elevation and immobilization in the treatment of cellulitis is to diminish the edema, which impedes the blood flow to an infected region. Elevation of the affected limb above the level of the heart is necessary to achieve optimal results. In the event of a lower extremity cellulitis, merely placing the affected limb on a chair while seated is not adequate because the abdominal contents still exert pressure on the lymphatic vessels in this position, thereby perpetuating the edema. In addition to the measures just described, this patient should receive a tetanus booster shot. Any patient with a bite or deep scratch wound who has not had a tetanus booster shot within the preceding 5 years should receive one.

What are the goals of the modern drug treatment of active pulmonary tuberculosis?

What factors are likely to promote relapse?

What factors are likely to foster the acquisition of drug-resistant disease?