Bacterial Pneumonia

– Christian Hoffmann –

Bacterial pneumonia occurs even with a relatively good immune status (above 200 CD4 T cells/µl). It is not as closely associated with immunodeficiency. Furthermore the decrease in incidence since the HAART era has been more moderate than for other opportunistic infections. Only recurring, radiologically and culturally detected acute pneumonia (more than one episode in the last 12 months) is considered AIDS-defining. As with HIV-negative patients, community-acquired pneumonia should be distinguished from nosocomial pneumonia. Travel history is important, particularly for community-acquired pneumonia.

The bacteria that are most frequently found to cause community-acquired pneumonia in HIV infected patients are Pneumococcus and Hemophilus influenza. Mycoplasma is important to consider, particularly in younger patients. Klebsiella, Staphylococcus aureus and Pseudomonas aeruginosa are other common pathogens. Legionella are rare.

Intravenous drug users develop community-acquired pneumonia significantly more often than other patient groups. Comorbidity, alcohol abuse and current smoking are other risk factors (Grau 2005). Therapy interruption and cigarette smoking were also major risk factors in SMART (Gordin 2008). Abstinence from smoking significantly reduces the risks of bacterial pneumonia (Bénard 2010). Earlier reports about increased incidences of bacterial pneumonia on a T-20 containing regimen have not been confirmed (Trottier 2005, Kousignian 2010). Low CD4 T cell counts and an existing liver cirrhosis are major risk factors for severe cases (Manno 2009, Madeddu 2010).

Nosocomial pneumonia is often caused by hospital germs (Klebsiella, Staphylo-coccus, Pseudomonas). In such cases, treatment depends on local resistance patterns and experience (Gant 2000, Vogel 2000).

Signs and symptoms/Diagnosis

Acute, usually high, fever and productive cough are typical. Breathing may be painful because of accompanying pleuritis, but real dyspnea is rare. Auscultation almost always allows distinction from PCP. If something can be heard, then PCP is unlikely. Chest radiography secures the diagnosis. CRP is significantly elevated, LDH usually normal. It is essential to take several blood cultures at body temperatures above 38.5˚C before starting treatment. A major problem regarding the blood culture is that diagnosis takes time (24-48 hours) and is not so sensitive. However it is the only procedure that allows a resistance test.  Sputum culture is a simple method allowing determination of etiology in approximately half of all cases – however, its overall utilization remains controversial and results strongly depend on the clinician’s experience (Cordero 2002). This also applies for the pneumococcal antigen determination in urine and the diagnosis of other specific viruses which are not recommended in current guidelines (Tessmer 2010).

Treatment

General

Treatment of bacterial pneumonia in HIV patients is similar to that in HIV-seronegative patients. Therapy should always begin empirically, without waiting for sputum or blood culture results. Many HIV patients with bacterial pneumonia can be treated as outpatients. Patients with poor immune status below 200 CD4 T cells should be hospitalized, as well as patients with high fever (above 39.5˚C), poor compliance, signs of organ failure, CNS disorders (confusion) or poor vital signs (tachypnea, tachycardia, hypotonia) and older patients (above 65 years).

Sufficient hydration is important in all patients. If patients remain in ambulatory care, then this is an indication that they should drink a lot (more than 2 l water daily). The use of supportive therapy with expectorants or mucolytics such as N-acetylcysteine or antitussives is controversial. On adequate therapy, improvement can be expected within 48-72 hours. If patients, especially the severely immunocompromised, have a persistent fever, then the treatment must be reconsidered after 72 hours, at the latest. It should be noted that the current first line therapies are not effective against Pseudomonas aeruginosa.

Medication

Different drugs are possible for ambulatory treatment. Even an attempt with penicillin may be justified in some circumstances – depending on local rates of Pneumococcus and Hemophilus influenzae resistance. It should be noted that HIV-infected patients frequently develop allergies.

Empiric treatment/prophylaxis of community-acquired bacterial pneumonia (daily doses) – there may be significant differences in price!
Outpatient   Duration: 7-10 days
Mild Amoxicillin +
clavulanic acid
1 tbl. at 875/125 mg tid
Mild Clarithromycin 1 tbl. at 500 mg bid
Mild Roxithromycin 1 tbl. at 300 mg qd
Mild Cefuroxim 1 tbl. at 500 mg bid
Mild Cefpodoxim 1 tbl. at 200 mg bid
Inpatient
Severe Piperacillin
(+ tazobactam)

+ macrolide

TazobacÒ 1 bottle at 4.5 g i.v. tid plus
roxithromycin 1 tbl. at 300 mg qd or clarithromycin 1 tbl. at 500 mg bid
Severe Ceftriaxon

+ macrolide

 

Cefriaxon 1 infusion. at 2 g qd i.v. plus              roxithromycin 1 tbl. at 300 mg qd or clarithromycin 1 tbl. at 500 mg bid
Severe Cefuroxim

+ macrolide

 

Cefuroxim 1 infusion at 1.5 g tid i.v. plus              roxithromycin 1 tbl. at 300 mg qd or clarithryomcin 1 tbl. at 500 mg bid
Prophylaxis Vaccination (pneu-mococcal poly-saccharide) Pneumovax 23pre-filled syringei.m.

Aminopenicillins are effective against Hemophilus influenza and various gram negatives. However, when combined with clavulanic acid, which is active against beta-lactamase-producing bacteria, they are associated with more gastrointestinal complaints. Newer oral cephalosporins have a broader spectrum against gram negatives, while at the same time having good efficacy against Pneumococcus and Hemophilus. They are, however, expensive.

Macrolides are advantageous for atypical bacteria such as Mycoplasma, Chlamydia and Legionella – but the proportion of macrolide-resistant Pneumococcus is increasing (14% in Germany). Efficacy is also limited in some Hemophilus strains.

For quinolones, it should be noted that ciprofloxacin has no or only weak efficacy against many important pathogens. Therefore only newer quinolones should be used. However, in 2009, a ‘Dear Doctor’ letter was sent to European health care professionals, describing the rare occurrence of fulminant hepatitis and the Stevens-Johnson syndrome or toxic epidermal necrolysis in patients using moxifloxacin. These side effects must be placed in the overall balance of pros and cons of moxifloxacin as compared to the alternatives.

If patients are hospitalized, then intravenous administration is possible initially. In these cases, at least two antibiotics should be combined.

Targeted treatment after isolation of the pathogen, and, in particular, treatment of nosocomial pneumonia, should depend on local resistance patterns and the recommendations of the in-house microbiologist.

Prophylaxis

The Pneumovax® vaccine provides effective protection. It should be utilized in all HIV patients with adequate immune status (above 200 CD4 T cells/µl). However, newer data suggest that Pneumovax® has a significant, independent protective effect against pneumococcal disease, regardless of CD4 lymphocyte count (Peñaranda 2007). Although it does not avert pneumonia in all cases it seems to have a positive effect on the further course of the treatment (Imaz 2009).

References

Bénard A, Mercié P, Alioum A, et al. Bacterial Pneumonia among HIV-infected patients: decreased risk after tobacco smoking cessation. ANRS CO3 Aquitaine Cohort, 2000-2007. PLoS One 2010, 5:e8896.

Cordero E, Pachon J, Rivero A, et al. Usefulness of sputum culture for diagnosis of bacterial pneumonia in HIV-infected patients. Eur J Clin Microbiol Infect Dis 2002, 21:362-7.

Franzetti F, Grassini A, Piazza M, et al. Nosocomial bacterial pneumonia in HIV-infected patients: risk factors for adverse outcome and implications for rational empiric antibiotic therapy. Infection 2006;34:9-16.

Gant V, Parton S. Community-acquired pneumonia. Curr Opin Pulm Med 2000, 6:226-33.

Gordin FM, Roediger MP, Girard PM, et al. Pneumonia in HIV-infected persons: increased risk with cigarette smoking and treatment interruption. Am J Respir Crit Care Med 2008, 178:630-6.

Grau I, Pallares R, Tubau F, et al. Epidemiologic changes in bacteremic pneumococcal disease in patients with human immunodeficiency virus in the era of highly active antiretroviral therapy. Arch Intern Med 2005;165:1533-40.

Imaz A, Falcó V, Peñaranda M, et al. Impact of prior pneumococcal vaccination on clinical outcomes in HIV-infected adult patients hospitalized with invasive pneumococcal disease. HIV Med 2009, 10:356-63.

Kousignian I, Launay O, Mayaud C, et al. Does enfuvirtide increase the risk of bacterial pneumonia in patients receiving combination antiretroviral therapy? J Antimicrob Chemother 2010, 65:138-44.

Madeddu G, Fiori ML, Mura MS. Bacterial community-acquired pneumonia in HIV-infected patients. Curr Opin Pulm Med 2010 Feb 11. [Epub ahead of print]

Manno D, Puoti M, Signorini L, et al. Risk factors and clinical characteristics associated with hospitalization for community-acquired bacterial pneumonia in HIV-positive patients according to the  presence of liver cirrhosis. Infection 2009, 37:334-9.

Penaranda M, Falco V, Payeras A, et al. Effectiveness of polysaccharide pneumococcal vaccine in HIV-infected patients: a case-control study. Clin Infect Dis 2007;45.

Rimland D, Navin TR, Lennox JL, et al. Prospective study of etiologic agents of community-acquired pneumonia in patients with HIV infection. AIDS 2002, 16:85-95.

Tessmer M. Ambulant erworbene untere Atemwegsinfektionen/ambulant erworbene Pneumonien bei erwachsenen Patienten. Arzneimitteltherapie 2010,28:60-7.

Trottier B, Walmsley S, Reynes J, et al. Safety of enfuvirtide in combination with an optimized background of antiretrovirals in treatment-experienced HIV-1-infected adults over 48 weeks. JAIDS 2005, 40:413-21.

Vogel F, Worth H, Adam D, et al. Rationale Therapie bakterieller Atemwegsinfektionen. Empfehlungen einer Expertengruppe der Paul-Ehrlich-Gesellschaft für Chemotherapie e.v. und der Deutschen Atemwegsliga. Chemotherapie Journal 2000, 1:3-23 Komplett im

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Filed under 11. Opportunistic Infections, Bacterial pneumonia, Part 3 - AIDS

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