Trench Fever


Practice Essentials

Trench fever is a clinical syndrome caused by infection with Bartonella quintana; the condition was first described during World War I. Contemporary B quintana disease, commonly referred to as urban trench fever, is typically found in homeless, alcoholic, and poor populations.

The human body louse Pediculus humanus var corporis is the major vector involved in trench fever transmission [12(see the image below).

Dorsal view of female body louse, Pediculus humanuDorsal view of female body louse, Pediculus humanus var corporis. This louse is a known vector responsible for transmission of epidemic typhus, trench fever, and Asiatic relapsing fever; it also causes dermatitic condition known as pediculosis. Image courtesy of Centers for Disease Control and Prevention.

Signs and symptoms

Classic symptoms of trench fever include the following:

  • Clinical incubation period of 3-48 days

  • Acute-onset fever in any of 3 distinct patterns, all of which are often associated with chills and diaphoresis: Abortive, relapsing (the most common pattern), or continuous

  • Acute-onset frontal or retro-orbital headache, often associated with a stiff neck and photophobia

  • Neuropsychiatric symptoms, such as weakness, depression, restlessness, and insomnia

  • Conjunctivitis

  • Dyspnea

  • Diffuse abdominal pain, often associated with anorexia, nausea, vomiting, weight loss, diarrhea, and constipation

  • Bone pain, particularly involving the shins; loin pain

  • Erythematous, macular rash

Urban trench fever typically includes 1 or more of these symptoms, but the presentation tends to be more variable.

Three additional syndromes are associated with B quintana infection, as follows:

  • Chronic lymphadenopathy – Enlarged cervical lymph nodes, without fever or other associated symptoms

  • Bacillary angiomatosis – characteristic skin lesions, with or without regional lymphadenopathy

  • B quintana endocarditis – Fever, new murmur, and heart failure; embolic phenomena

Characteristics of classic trench fever were fairly consistent, as follows:

  • Fever up to 104°F

  • Toxic initial appearance associated with prostration

  • Characteristic blanching, erythematous, macular rash

  • Conjunctivitis at the onset of illness

  • Paroxysmal tachycardia, paralleling the fever and exacerbated with exercise

  • Splenomegaly in more prolonged courses

  • Bone and muscle tenderness

  • Loss of Achilles reflex

  • Associated lice infestation

Physical findings of urban trench fever are more variable, but tend to include the following:

  • Presence of rash, fever, conjunctivitis, bone tenderness, splenomegaly, and neuropsychiatric signs vary, and the characteristic signs are generally less prevalent than in the classic cases

  • Nonspecific findings such as weight loss and weakness

Common findings in associated syndromes of urban trench fever are as follows:

  • Chronic lymphadenopathy – Lymphatic involvement of the cervical and mediastinal lymph nodes; afebrile and otherwise asymptomatic

  • Bacillary angiomatosis (immunocompetent) – Presence of one or more papules that progress to nodules that may be localized or disseminated; associated regional adenopathy; afebrile

  • Bacillary angiomatosis (immunocompromised) – Lesions are generally more widespread and are more likely to involve visceral organs than in the immunocompetent patient

  • B quintana endocarditis – Fever and murmur; typically involves the left-sided heart valves; embolic events; possible heart failure

Many patients with microbiologic or serologic evidence of B quintana infection are asymptomatic.

See Presentation for more details.

Diagnosis

B quintana infection is difficult to diagnose in the laboratory. The following studies may be useful:

  • Blood cultures

  • Immunofluorescent assays (IFAs) for immunoglobulin M (IgM) and immunoglobulin G (IgG) antibody levels for both B quintana and Bartonella henselae

  • Enzyme immunoassay (EIA) and enzyme-linked immunosorbent assay (ELISA)

  • Polymerase chain reaction (PCR)–based genomic assays and histochemical stains for direct detection of Bartonella DNA in both tissue and blood

  • Biopsy of skin, lymph node, cardiac valve, or other tissue

See Workup for more details.

Management

Current antibiotic recommendations for each of the identified clinical syndromes associated with B quintana in immunocompetent patients are as follows:

  • Trench fever/urban trench fever – Doxycycline 100 mg PO twice daily for 28 days plus gentamicin 3 mg/kg/day IV for 14 days; macrolides and ceftriaxone are also effective

  • Chronic B quintana bacteremia – Doxycycline 100 mg PO twice daily for 28 days and gentamicin 3 mg/kg/day IV for 14 days; in some cases, longer therapy (up to 4 years) may be required; serial cultures demonstrating eradication of the bacteremia are pivotal in determining duration of therapy

  • Chronic lymphadenopathy – Erythromycin 500 mg PO 4 times daily for 3 months (first-line therapy) or doxycycline 100 mg PO twice daily for 3 months (alternative); in difficult cases, gentamicin 3 mg/kg/day IV for 14 days can be added

  • Bacillary angiomatosis – Erythromycin 500 mg PO 4 times daily for 3 months (first-line therapy) or doxycycline 100 mg PO twice daily for 3 months (alternative); in refractory cases, gentamicin 3 mg/kg/day IV for 14 days can be added; fluoroquinolones and ceftriaxone may also be considered

  • B quintana endocarditis – Doxycycline 100 mg PO twice daily for 6 weeks plus gentamicin 3 mg/kg/day IV for 14 days; if culture results are negative, ceftriaxone should be added

Surgical biopsy may help diagnose B quintana endocarditis, lymphadenopathy, or bacillary angiomatosis. Valve replacement surgery is required in most cases of B quintana endocarditis.

See Treatment and Medication for more details.

Background

Trench fever is a clinical syndrome caused by infection with Bartonella quintana. The condition was first described during World War I, when it affected nearly 1 million soldiers. [3412It has been known by several different names, including quintan fever, 5-day fever, shin bone fever, tibialgic fever, Wolhynia fever, and His-Werner disease.

DNA studies have demonstrated that many soldiers in Napoleon’s Grand Army at Vilnius in the 19th century were infected with B quintana. In addition, B quintana DNA was found in a 4000-year-old human tooth in Roaix, France. [56Reports of trench fever outbreaks stopped after World War I and then reappeared transiently on the Eastern Front in Europe during World War II.

By the end of World War I, the human body louse Pediculus humanus was recognized as the likely vector for trench fever transmission. [12Rickettsia -like organisms in the body and feces of P humanus were postulated to be the cause. In 1969, Vinson et al successfully cultivated the causative organism (then called Rickettsia quintana) from a sick patient and reproduced the disease by inoculating healthy volunteers. [7The organism was briefly placed in the genus Rochalimaea before being reclassified as Bartonella quintana in 1993.

During World War I, trench fever was characterized by the abrupt onset of fever, malaise, myalgias, headache, transient macular rashes of the torso, pain in the long bones of the leg (shins), and splenomegaly. [8912341011Typical periodic cycles of fever, chills, and sweats occurred at 5-day intervals, resulting in prolonged disability lasting 3 months or longer in young soldiers. However, no deaths attributable to trench fever have ever been reported.

Over the past 3 decades, Bartonella species have emerged as a cause of bacteremia, angioproliferative disease (eg, bacillary angiomatosis), and endocarditis in patients with and without HIV infection. In 1995, B quintana was found to cause bacteremia in 10 homeless, HIV-negative alcoholics. [12In 1999, B quintana endocarditis was described in 3 HIV-negative homeless alcoholic men. [13These cases suggest that B quintana disease is not limited to wartime outbreaks or immunocompromised persons.

Subsequently, sporadic cases and small clusters of B quintana infection have been described worldwide and appear to be associated with poor sanitation, poor hygiene, alcoholism, and malnutrition—all of which are commonly seen in both classic and urban trench fever cases. Seroprevalence studies suggest that B quintana infection is more common than is clinically recognized and that many infections are subclinical.

The term urban trench fever is applied to contemporary B quintana disease. Urban trench fever is typically found in homeless, alcoholic, and poverty-stricken populations, among whom poor personal hygiene is common. The infection affects both immunocompetent and immunocompromised persons. Some (but not all) persons with urban trench fever have evidence of louse infestation.

The spectrum of disease associated with B quintana infection includes asymptomatic infection, urban trench fever, angioproliferative disease, chronic lymphadenopathy, bacteremia, and endocarditis. [91415]

Pathophysiology

The human body louse P humanus var corporis is the major vector involved in trench fever transmission (see the image below). [12]

Dorsal view of female body louse, Pediculus humanuDorsal view of female body louse, Pediculus humanus var corporis. This louse is a known vector responsible for transmission of epidemic typhus, trench fever, and Asiatic relapsing fever; it also causes dermatitic condition known as pediculosis. Image courtesy of Centers for Disease Control and Prevention.

After B quintana is introduced into the human body, it invades erythrocytes and endothelial cells, where it is protected from the host’s humoral immune response. [16Intraerythrocytic B quintana colonization is largely limited to human beings, [914while the invasion of vascular endothelial cells is less species-specific. [17Monocytes from homeless individuals with chronic B quintana bacteremia have been shown to overproduce interleukin (IL)–10, resulting in an attenuated immune response that may facilitate the bacterial persistence. [18These same patients generate a poorer humoral response than patients with endocarditis, in whom the inflammatory response is more dramatic and bacteremia less frequent. [19]

Once the organism invades and begins to multiply within endothelial cells, proinflammatory cytokines are activated, apoptosis suppressed, and vascular proliferation initiated. [20These changes result in systemic symptoms, bacteremia, endovascular infection, and lymphatic enlargement. The relationship between the endothelial vascular proliferation and the destructive valvular lesions of B quintana endocarditis is unknown. A potential connection might be the presence of variably expressed outer-membrane proteins in some strains of B quintana. These proteins induce secretion of vascular endothelial growth factor and are associated with increased rates of invasion. [21]

Despite this possible immunologic association, the histologic features of these two clinical variants differ. [9The pathogenesis of B quintana –associated disease suggests that bacteremia is an early occurrence common to all of the various syndromes attributed to it. In some patients, the bacteremia lasts for a few days, whereas, in others, it lasts for months to years. [14]

Etiology

B quintana causes both trench fever and urban trench fever. [97Humans are the predominant reservoir of the pathogen, although infection has been documented in some nonhuman primates and in cats. [22232425In infected persons, the organisms can be found in human blood, tissues (particularly skin), and urine. [9]

B quintana bacteremia may be intermittent or prolonged for years, suggesting that blood-sucking arthropods are efficient transmitters of B quintana infection. [1614External parasitic infestations are also associated with conditions of squalor. Although the body louse P humanus is the major vector for both trench fever and urban trench fever, its presence is not always demonstrated in patients with urban trench fever. [71326]

Breaks in the skin contaminated by louse feces and arthropod bites are documented portals of entry. Other possible vectors include mites, ticks, and fleas. [9A 2014 study showed that cat fleas (Ctenocephalides felis) can ingest B quintana and release viable bacteria into their feces. [27Contamination of mucous membranes, transfusion, transplantation, and IV drug abuse are also potential avenues of entry. Human-to-human transmission of trench fever has not been described.

Epidemiology

Predisposing factors for B quintana infection include war, famine, malnutrition, homelessness, alcoholism, intravenous (IV) drug abuse, and poor hygiene.

United States statistics

B quintana was found in the lice of 33.3% of body lice–infested and 25% of head lice–infested homeless persons in California. [28In one study, 20% of the patients in a downtown Seattle clinic that serves a homeless indigent population had microimmunofluorescent antibody titers of 1:64 or greater to Bartonella species. [29Multivariate analysis of these patients revealed that alcohol abuse was the only independent variable associated with seropositivity. It is difficult, however, to ascertain the true incidence of urban trench fever, as most infected individuals are asymptomatic. Moreover, the disease occurs sporadically and in small clusters of homeless persons.

International statistics

B quintana –related illness has been found on every continent except Antarctica. Well-performed seroprevalence studies have identified patients with B quintana antibodies in France, Greece, Sweden, Japan, Brazil, Croatia, and Peru. [19303132333435Cases of culture-negative endocarditis with antibody titers positive for B quintana have been reported in Europe, Australia, Japan, Tunisia, and India. [3637383940]

Age-, sex-, and race-related demographics

Whereas trench fever described during wartime typically affected young soldiers, urban trench fever typically affects middle-aged adults. Rare cases of Bartonella endocarditis and central nervous system (CNS) infection have been described in children.

Because trench fever was historically an infection of soldiers, most of the cases documented during World Wars I and II were in males. Cases of urban trench fever described since 1995 have also predominantly involved males, reflecting the disproportionate representation of males in the homeless alcoholic population.

No convincing data suggest that urban trench fever or other syndromes caused by B quintana infection have a racial or ethnic predilection.

Prognosis

In most immunocompetent hosts, B quintana infection is self-limited unless endocarditis occurs. In immunocompromised hosts, however, B quintana infection tends to be more severe and may result in death.

During World War I, trench fever resulted in significant morbidity and prolonged disability but no recognized mortality. Contemporary descriptions of B quintana endocarditis in homeless alcoholic males have found mortality rate to be as high as 12%, with most deaths related to complications of endocarditis or to the surgery used in its treatment. [4142]

Patient Education

Patients should be educated about practicing good personal hygiene and improving their living conditions. Vector control of the body louse should also be explained

CLINICAL PRESENTATION


History

Trench fever

During World War I, trench fever was recognized and precisely described as a distinct syndrome by several physicians. [83412The clinical incubation period was 3-48 days. [23Associated lice infestation was common. Young soldiers with trench fever would experience headache, relapsing fevers, shin pain, truncal rash, and splenomegaly. Most patients could vividly remember the specific time of symptom onset.

The differential diagnoses of the initial symptoms associated with trench fever included typhoid feverepidemic typhusinfluenza, and meningitis. Although there was no recognized mortality, it caused serious and prolonged disability.

Headaches were sudden in onset and were described as frontal or retro-orbital. They were often associated with a stiff neck and photophobia, raising the possibility of meningitis. Other neuropsychiatric symptoms included weakness, depression, restlessness, and insomnia. Many patients with trench fever would experience severe prostration.

The dramatic onset of fever coincided with the onset of headaches. Temperatures were often as high as 104°F and were associated with malaise, chills, and sweats. Fever occurred in one of 3 distinct patterns, as follows:

  • Abortive fever: Temperature elevation lasting several days, after which the fever abated and disappeared

  • Relapsing/quintan fever: The most commonly observed pattern occurred at 5-day intervals (range, 4-8 days), giving rise to the names quintan fever and 5-day fever; the fever would progressively increase during the first episode and then progressively improve during subsequent paroxysms; recurrent fever months to years after the original defervescence have been reported

  • Continuous fever: Lasted for the duration of the disease

Bone pain, particularly involving the shins, progressively worsened throughout the duration of illness. The pain became dramatically worse with exercise and could be so severe that it prevented patients from even changing position in bed. Another common site of pain was the loin with radiation to the lower extremities or into the upper back.

Gastrointestinal (GI) symptoms of trench fever would begin with diffuse abdominal pain, often associated with anorexia, nausea, vomiting, weight loss, diarrhea, and constipation.

Conjunctivitis was another common initial symptom. An erythematous truncal rash and tachycardia would develop during the febrile episodes. Dyspnea could also be present.

Urban trench fever

Urban trench fever has been characterized by one or more of the symptoms described above, but the presentation tends to be more variable. [94336121441Urban trench fever occurs in homeless and alcoholic persons who exhibit poor personal hygiene. The presence of lice and other external parasites is less prevalent in these individuals. Headaches, conjunctivitis, relapsing fever, and shin pain have been documented, whereas abdominal and neurologic symptoms appear to be uncommon.

Associated syndromes

The descriptions of other syndromes associated with B quintana infection over the past 30 years were unknown to physicians during World War I. A large percentage of persons with B quintana infection may be asymptomatic, and those with syndromes consistent with infection may have negative blood culture results. Typical manifestations of these associated syndromes are as follows:

  • Chronic lymphadenopathy - enlarged cervical lymph nodes, without fever or other associated symptoms [9]

  • Bacillary angiomatosis - characteristic skin lesions, with or without regional lymphadenopathy, without systemic symptoms [14]

  • B quintana endocarditis - fever, new murmur, and heart failure; 20% demonstrate embolic sequelae [42]

Chronic B quintana bacteremia is occasionally accompanied by all of the syndromes described above and may last for years. [19]

Physical Examination

Trench fever

The physical findings of trench fever during World War I were fairly consistent. Infected persons experienced an abrupt onset of fever (up to 104°F), associated with chills and diaphoresis. Patients would initially exhibit a toxic appearance associated with prostration. A furred or coated tongue was common. Some patients were able to continue with their daily activities and recover after a short fastigium, but most would develop a significant disability for months.

Patients with trench fever exhibited a characteristic nonpruritic, blanching, erythematous, macular rash that typically started on the trunk and extended as far as the abdomen, neck, and proximal extremities. The rash accompanied the fever, recurring with each febrile paroxysm. Although the rash was not pruritic, coexisting body louse and scabies infestations caused pruritus and excoriations.

The vast majority of patients with trench fever developed conjunctivitis at the onset of illness. Photophobia was common. Paroxysmal tachycardia generally paralleled the fever. Splenomegaly was common in those with more prolonged courses of illness. Bone and muscle tenderness accompanied the shin pain and became progressively more severe and debilitating as the disease progressed. Loss of the Achilles reflex, a manifestation of peripheral neuropathy, was common.

Urban trench fever

The physical findings of urban trench fever are more variable. Rash, fever, conjunctivitis, bone tenderness, splenomegaly, and neurologic signs (eg, absent Achilles reflexes) have been documented but are generally less prevalent than in the case descriptions from World War I. Nonspecific findings such as weight loss and weakness have been reported. Lastly, many patients with microbiologic or serologic evidence of B quintana infection are asymptomatic.

Associated syndromes

Patients with chronic lymphadenopathy usually have lymphatic involvement of the cervical and mediastinal lymph nodes. They do not experience fever and are otherwise asymptomatic.

Bacillary angiomatosis typically presents with one or more papules that progress to nodules and may be confined to one or more anatomic regions. In immunocompromised patients, however, lesions tend to be more widespread and are more likely to involve viscera such as the liver, spleen, and GI tract. The lesions are red, purple, or nonpigmented and can be superficial or subcutaneous. They may be mobile or fixed to underlying structures (eg, bone). Regardless of appearance, they bleed profusely when punctured or incised. Associated regional adenopathy is common.

Immunocompetent patients with bacillary angiomatosis are typically afebrile. The same lesions occurring in immunocompromised patients are generally more widespread and are more likely to involve visceral organs such as the liver, spleen, and GI tract.

Patients with B quintana endocarditis present with fever and murmur. Lesions typically involve the left-sided heart valves, resulting in mitral insufficiency, aortic insufficiency, or both. Right-sided cardiac involvement is unusual. Heart failure may occur, and embolic lesions develop in as many as 20% of patients. [42]

Interestingly, Koo et al implicated B Quintana in a culture-negative mycotic abdominal aortic aneurysm in a patient with chronic back pain but without other signs of infection. The diagnosis was made by polymerase chain reaction (PCR) and mass spectrometry of tissue sample. 

DDx


Diagnostic Considerations

In addition to the conditions listed in the differential diagnosis, other problems to be considered include the following:

Differential Diagnoses

TREATMENT & MANAGEMENT

Approach Considerations

No well-designed, double-blinded, controlled trials have documented the best antibiotic regimen for B quintana infection and its associated syndromes (including trench fever) in immunocompetent patients. Most therapeutic recommendations are based on anecdotal clinical experience.

Pregnancy affects the appropriate choice of antibiotics for treatment. Teratogenic and congenital effects of maternal infection are unknown, as is the impact on pregnancy.

Initial management of severe Bartonella infections, including trench fever and urban trench fever, may require inpatient management. Generally, the consolidation phase of treatment can be provided on an outpatient basis.

An infectious disease specialist may be consulted for help with diagnosis and treatment. A microbiology laboratory may be consulted for help with blood and tissue specimen handling to ensure optimal culture, serologic, and PCR-genomic testing.

Pharmacologic Therapy

In the laboratory, B quintana appears to be sensitive to advanced-generation beta-lactams, chloramphenicol, macrolides, tetracyclines, fluoroquinolones (though not ciprofloxacin), aminoglycosides, rifampin, and trimethoprim-sulfamethoxazole. [144849]

Microbiologic susceptibility studies may not accurately predict clinical efficacy, in that B quintana seems to respond clinically to bacteriostatic agents such as doxycycline, erythromycin, and azithromycin. [23Only gentamicin is bactericidal in vitro. [50Because gentamicin does not achieve bactericidal levels within human erythrocytes, it is not believed to be optimal for monotherapy, but it is regularly used in combination with doxycycline.

For treatment of serious or complicated infections, it is critical to use combination therapy with two agents known to exhibit good in vitro activity against B quintana. [48Based on reports of successful treatment in immunocompromised patients, which are mostly anecdotal, longer treatment regimens in conjunction with close clinical and microbiologic follow-up is recommended.

The following are current recommendations for each of the identified clinical syndromes associated with B quintana in immunocompetent patients:

  • Trench fever/urban trench fever – For uncomplicated disease, doxycycline 100 mg orally (PO) twice daily for 28 days and gentamicin 3 mg/kg/day intravenously (IV) for 14 days [48; macrolides and ceftriaxone are also effective [92313]

  • Chronic B quintana bacteremia – Doxycycline 100 mg PO twice daily for 28 days and gentamicin 3 mg/kg/day IV for 14 days [5148; in some cases, longer therapy (up to 4 years) may be required [14; serial cultures demonstrating eradication of the bacteremia are pivotal in determining duration of therapy

  • Chronic lymphadenopathy – Erythromycin 500 mg PO 4 times daily for 3 months (first-line therapy) or doxycycline 100 mg PO twice daily for 3 months (alternative) [489; in difficult cases, gentamicin 3 mg/kg/day IV for 14 days can be added

  • Bacillary angiomatosis – Erythromycin 500 mg PO 4 times daily for 3 months (first-line therapy) or doxycycline 100 mg PO twice daily for 3 months (alternative) [48; in refractory cases, gentamicin 3 mg/kg/day IV for 14 days can be added [9; fluoroquinolones and ceftriaxone may also be considered

  • B quintana endocarditis – Doxycycline 100 mg PO twice daily for 6 weeks plus gentamicin 3 mg/kg/day IV for 14 days [48; if culture results are negative, ceftriaxone should be added; however, a recent meta-analysis did not find this superior to other combinations [52; most patients require valvular heart surgery [4142]

Surgical Intervention

Surgical biopsy may be used when necessary to establish a definitive diagnosis of B quintana endocarditis, lymphadenitis, or bacillary angiomatosis.

In addition to numerous descriptions of small numbers of patients with B quintana endocarditis, 2 large studies (both performed by the same group of investigators) have described the treatment and outcomes of the disease. [4142The findings of these studies suggested that, in most cases of B quintana endocarditis, valvular cardiac surgery is required.

Diet and Activity

No dietary restrictions are necessary in patients with Bartonella infection, including trench fever and urban trench fever.

No activity restrictions are necessary unless a patient has cardiac failure due to Bartonella endocarditis or its complications. Patients should take steps to improve their hygiene and living conditions. Individuals should avoid donating blood or tissue if they are at risk for Bartonella infection.

Prevention

B quintana infection can be prevented via avoidance or rapid treatment of lice infestations, as follows: [145354]

  • Providing facilities for bathing
  • Providing facilities for laundry
  • Insecticide application to or frequent boiling of bedding in shelters
  • Ivermectin treatment for lice infestation
  • Prompt diagnosis and treatment of​B quintana infection to decrease the reservoir for this pathogen
MEDICATION

Medication Summary

The goal of antibiotic therapy is to eradicate all forms of B quintana infection, minimizing morbidity and mortality.

Antibiotics

Class Summary

Antibiotic therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting.

Doxycycline (Vibramycin, Adoxa, Monodox)

Doxycycline is a synthetically derived broad-spectrum antibiotic in the tetracycline class. It is almost completely absorbed, is concentrated in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations. Doxycycline is bacteriostatic, and its mechanism of action is inhibition of protein synthesis through binding to the 50S subunit of the ribosome. Tetracyclines, as a class, evoke a dramatic response, with rapid disappearance of the associated symptoms and defervescence (usually in 1-2 days).

Ceftriaxone (Rocephin)

Ceftriaxone is a third-generation cephalosporin with broad-spectrum gram-negative activity; it has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. Ceftriaxone is bactericidal; it arrests bacterial growth by binding to 1 or more of the penicillin-binding proteins.

Gentamicin

Gentamicin is an aminoglycoside antibiotic used for coverage of gram-negative bacteria, including Pseudomonas species. It is synergistic with beta-lactamase against enterococci. It interferes with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits.

Dosing regimens for gentamicin are numerous and are adjusted on the basis of creatinine clearance and changes in the volume of distribution, as well as the body space into which the agent must distribute. Doses may be given either intravenously or intramuscularly. Each regimen must be followed by at least a trough level drawn on the third or fourth dose, 30 minutes before dosing; a peak level may be drawn 30 minutes after a 30-minute infusion.

Gentamicin is used in combination with both an agent that covers gram-positive organisms and one that covers anaerobes. It may be considered if penicillins or other less toxic drugs are contraindicated, if there are particular clinical indications for its use, or if a patient has a mixed infection caused by susceptible staphylococci and gram-negative organisms.

Erythromycin (E.E.S., Ery-Tab, Erythrocin)

Erythromycin is a highly bacteriostatic macrolide antibiotic isolated from a Streptomyces strain. Its spectrum is between those of penicillin and tetracyclines. The mechanism of action involves binding to the 50S ribosomal subunit and inhibiting microbial protein synthesis.